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Antimicrobial potential of a gel containing hydrogen peroxide and hyaluronic acid 2 2 No abstract provided as this is a letter to the editor  189 192 2020/09/18 1399/6/28 2021/01/31 1399/11/12 Jyothi Tadakamadla Jyothi Tadakamadla School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia Australia jyothi.tadakamadla@griffithuni.edu.au Elisa Boccalari Elisa Boccalari Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan; Milan, Italy Italy Cinzia Maspero Cinzia Maspero Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan; Milan, Italy Italy cinzia.maspero@unimi.it Abbasi A, Pakravan N, Hassan Z M. Hyaluronic acid optimises therapeutic effects of hydrogen peroxide-induced oxidative stress on breast cancer. Journal of Cellular Physiology 2020: 1-21.##Akima R. New Enzyme-Targeting Radiosensitizer (KORTUC) Containing Hydrogen Peroxide & Sodium Hyaluronate for Intra-Tumoral Injection Using Mice Transplanted with SCC VII Tumor. International Journal of Cancer and Clinical Research 2016; 3.##Bassetti M, Vena A, Croxatto A, Righi E, Guery B. How to manage Pseudomonas aeruginosa infections. Drugs in context 2018; 7: 212527-212527.##Capizzi R, Landi F, Milani M, Amerio P. Skin tolerability and efficacy of combination therapy with hydrogen peroxide stabilized cream and adapalene gel in comparison with benzoyl peroxide cream and adapalene gel in common acne. A randomized, investigator-masked, controlled trial. Br J Dermatol 2004; 151: 481-4.##Chang C M, Lee H C, Lee N Y, Lee I W, Wu C J, Chen P L, et al. Community-acquired Klebsiella pneumoniae complicated skin and soft-tissue infections of extremities: emphasis on cirrhotic patients and gas formation. Infection 2008; 36: 328-34.##Gallagher J J, Williams-Bouyer N, Villarreal C, Heggers J P, Herndon D N. Chapter 12 - Treatment of infection in burns. In: Herndon DN, editor. Total Burn Care (Third Edition). Edinburgh: W.B. Saunders, 2007: 136-176.##Hernandez P, Sager B, Fa A, Liang T, Lozano C, Khazzam M. Bactericidal efficacy of hydrogen peroxide on Cutibacterium acnes. Bone & joint research 2019; 8: 3-10.##Jegasothy S M, Zabolotniaia V, Bielfeldt S. Efficacy of a New Topical Nano-hyaluronic Acid in Humans. The Journal of clinical and aesthetic dermatology 2014; 7: 27-29.##Koo H, Andes D R, Krysan D J. Candida-streptococcal interactions in biofilm-associated oral diseases. PLoS pathogens 2018; 14: e1007342-e1007342.##Kühbacher A, Burger-Kentischer A, Rupp S. Interaction of Candida Species with the Skin. Microorganisms 2017; 5: 32.##Lee D H, Oh I Y, Koo K T, Suk J M, Jung S W, Park J O, et al. Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum. J Cosmet Laser Ther 2015; 17: 20-3.##Linley E, Denyer S P, McDonnell G, Simons C, Maillard J-Y. Use of hydrogen peroxide as a biocide: new consideration of its mechanisms of biocidal action. Journal of Antimicrobial Chemotherapy 2012; 67: 1589-1596.##Milani M, Bigardi A, Zavattarelli M. Efficacy and safety of stabilised hydrogen peroxide cream (Crystacide) in mild-to-moderate acne vulgaris: a randomised, controlled trial versus benzoyl peroxide gel. Curr Med Res Opin 2003; 19: 135-8.##Nobbs A H, Shearer B H, Drobni M, Jepson M A, Jenkinson H F. Adherence and internalization of Streptococcus gordonii by epithelial cells involves β1 integrin recognition by SspA and SspB (antigen I/II family) polypeptides. Cellular Microbiology 2007; 9: 65-83.##Pavicic T, Gauglitz G G, Lersch P, Schwach-Abdellaoui K, Malle B, Korting H C, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. J Drugs Dermatol 2011; 10: 990-1000.##Schianchi R, Nazzaro G, Veraldi S. Treatment of molluscum contagiosum with hydrogen peroxide. Clin Exp Dermatol 2018; 43: 66-67.##Veraldi S, Micali G, Berardesca E, Dall'Oglio F, Sinagra J L, Guanziroli E. Results of a Multicenter, Randomized, Controlled Trial of a Hydrogen Peroxide-based Kit versus a Benzoyl Peroxide-based Kit in Mild-to-moderate Acne. The Journal of clinical and aesthetic dermatology 2016; 9: 50-54.## ##

Molecular mechanisms and signaling pathways involved in immunopathological events of COVID-19 2 2 Introduction: COVID-19, a novel coronavirus that causes severe acute respiratory syndrome (SARS-CoV-2), is currently regarded as the most serious viral disease. During corona infection, viruses bind to host proteins and employ a variety of cellular pathways for their own purposes. Cell signaling is important for the regulation of cellular function. SARS-CoV-2 infection alters multiple signal transduction pathways that are critical for cell survival. The virus causes a severe and prolonged period of hypercytokinemia with misusing of these signaling cascades. Hyperactivation of the host immune system after infection with SARS-CoV-2 is the main cause of death in COVID-19 patients. Thus, to develop effective therapeutic approaches, it is necessary to first understand the problem and the underlying molecular pathways implicated in host immunological function/dysfunction. A number of intracellular signaling cascades have been implicated in infected cell pathways, including MAPK pathway, NF-κB pathway, JAK–STAT signaling pathway, PI3K/AKT/mTOR pathway and TLRI signaling cascades. Here, we have presented the molecular insights on the potential mechanisms involved in immunopathological events of COVID-19. 193 205 2020/09/182021/04/13 1400/1/24 2021/01/312021/07/26 1400/5/4 Ali Asghar Peyvandi Ali Asghar Peyvandi Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Somayeh Niknazar Somayeh Niknazar Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran niknazar@sbmu.ac.ir Fatemeh Zare Mehrjerdi Fatemeh Zare Mehrjerdi Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran Iran Hojjat-Allah Abbaszadeh Hojjat-Allah Abbaszadeh Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Shahrokh Khoshsirat Shahrokh Khoshsirat Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran Maryam Peyvandi Maryam Peyvandi Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Iran SARS-CoV-2 Infection Signal transduction pathways Cytokine storm. 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A study of adverse drug reactions and potential drug-drug interactions in the patients attending the Psychiatric Outpatient Department in a Tertiary Care Teaching Hospital: a cross-sectional study 2 2 Introduction: The objective of this study was to record and analyze the adverse drug reactions (ADRs) due to psychotropic drugs and the potential drug-drug interactions (pDDIs) amongst different psychotropic drugs as well as pDDIs between psychotropic drugs and other co-prescribed drugs by using Medscape software (online). Methods: A cross sectional study was carried out in patients visiting the Psychiatric Outpatient Department of a Tertiary Care Teaching Hospital. Total 500 prescriptions were analysed for the ADRs and pDDIs. Results: Total 37 ADRs were observed in 32 (6.4%) patients. Antipsychotics was the most common group and olanzapine was the most common psychotropic drug suspected of causing ADRs. Tremors was the most common ADR observed. All of the ADRs were nonserious and were in a “Recovering” state when the data was collected. Total 1051 pDDIs were observed in all the 500 prescriptions surveyed, out of which 361 prescriptions were showing at least one pDDI. Conclusion: The overall incidence of ADRs was not very high (6.4%), which reiterates the judicious use of the drugs in the study setting. Majority of prescriptions had only 1-2 pDDIs per prescription. 206 213 2020/09/182021/04/132020/09/27 1399/7/6 2021/01/312021/07/262021/01/17 1399/10/28 Adit Deshmukh Adit Deshmukh Department of Pharmacology, B. J. Government Medical College and Sassoon General Hospital, Pune, India India Sangeeta Dabhade Sangeeta Dabhade Department of Pharmacology, B. J. Government Medical College and Sassoon General Hospital, Pune, India India sangeetadr99@gmail.com Adverse drug reactions Drug interactions Psychotropic drugs Olanzapine Causality. Abebaw D, Haile K, Kassaw C, Belete A, Fanta T, Azale T, et al. Pattern of rational use of psychotropic drugs for people with severe mental illness in a mental specialized hospital in Addis Ababa, Ethiopia: a mixed method study. J Fam Med 2016; 3: 1099.##American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Fifth Edition. Arlington, VA: American Psychiatric Association; 2013. https://doi.org/10.1176/appi.books.9780890425596##English BA, Dortch M, Ereshefsky L, Jhee S. Clinically significant psychotropic drug-drug interactions in the primary care setting. Curr Psychiatry Rep 2012; 14: 376-90. https://doi.org/10.1007/s11920-012-0284-9##Grover S, Kumar V, Avasthi A, Kulhara P. An audit of first prescription of new patients attending a psychiatry walk-in-clinic in north India. Indian J Pharmacol 2012; 44: 319-25. https://doi.org/10.4103/0253-7613.96302##Gurung A, Jaju JB, Pawar GR, Dharmadhikari SC, Solunke RR. Study of drug utilization pattern and adverse drug reactions of psychotropic drugs in psychiatric inpatient department of tertiary care hospital. Int J Basic Clin Pharmacol 2018; 7: 259-65. https://doi.org/10.18203/2319-2003.ijbcp20180095##Hotha PP, Jadav SP, Trivedi HR. Adverse drug reactions: a retrospective review of hospitalized psychiatric patients at tertiary care hospital. Int J Basic Clin Pharmacol 2016; 5:2051-60. https://doi.org/10.18203/2319-2003.ijbcp20163235##Indian Pharmacopoeia Commission, Ghaziabad, 2014. Guidance document for spontaneous adverse drug reaction reporting. Version 1.0 Chapter 3, Reporting of Adverse Drug Reactions; p. 10-18.##Ismail M, Iqbal Z, Khattak MB, Javaid A, Khan MI, Khan TM, et al. Potential drug-drug interactions in psychiatric ward of a tertiary care hospital: prevalence, levels and association with risk factors. Trop J Pharm Res 2012; 11: 289-96. https://doi.org/10.4314/tjpr.v11i2.17##Medscape Drug Interaction Checker. Available from: http://reference.medscape.com/drug-interactionchecker (Cited 6th August 2016).##Monteiro NM. Addressing mental illness in Africa: global health challenges and local opportunities. Comm Psych Glob Persp 2015; 1: 78-95.##Mudhaliar MR, Ghouse IS, Sadubugga P, Narala SR, Chinnakotla V, Yendluri P. Psychotropic drug utilization in psychiatric outpatient department of a tertiary care teaching hospital in India. Int J Res Med Sci 2017; 5: 1612-6. https://doi.org/10.18203/2320-6012.ijrms20171274##Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of Adverse Drug Reactions. Clin Pharmacol Ther 1981; 30: 239-45. https://doi.org/10.1038/clpt.1981.154##Perumal VM, Bouddh SK, Nirmal SR, Deshpande A, Singh J, Prabhu N. Drug utilization study and prescribing patterns in psychiatry patients at a tertiary care hospital. Int J Basic Clin Pharmacol. 2018; 7: 774-7. https://doi.org/10.18203/2319-2003.ijbcp20181185##Prajapati HK, Joshi ND, Trivedi HR, Parmar MC, Jadav SP, Parmar DM, et al. Adverse drug reaction monitoring in psychiatric outpatient department of a tertiary care hospital. Natl J Integr Res Med 2013; 63: 15-48.##Sandson NB, Armstrong SC, Cozza KL. An overview of psychotropic drug-drug interactions. Psychosomatics 2005; 46: 464-94. https://doi.org/10.1176/appi.psy.46.5.464##Sengupta G, Bhowmick S, Hazra A, Datta A, Rahaman M. Adverse drug reaction monitoring in psychiatry out-patient department of an Indian teaching hospital. Indian J Pharmacol 2011; 43: 36-9. https://doi.org/10.4103/0253-7613.75664##Sharma T, Vishwakarma K, Dhasmana DC, Gupta R, Kalra J, Sharma U. Adverse drug reaction monitoring in psychiatry outpatient department of a tertiary care teaching hospital. JK Science 2014; 16: 156-60.##Solanke B, Mahatme MS, Dakhale G, Hiware S, Shrivastava M, Waradkar P. Adverse drug reaction profile at psychiatry out-patient department of a tertiary referral centre in Central India. Int J Basic Clin Pharmacol 2013; 2: 341-3. https://doi.org/10.5455/2319-2003.ijbcp20130623##Sridhar SB, Al-Thamer SS, Jabbar R. Monitoring of adverse drug reactions in psychiatry outpatient department of a Secondary Care Hospital of Ras Al Khaimah, UAE. J Basic Clin Pharma 2016; 7: 80-86. https://doi.org/10.4103/0976-0105.183263##Suspected Adverse Drug Reaction Reporting Form. Available from: https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/Pdf documents/Consumer_Section_PDFs/ADRRF_2.pdf##Tesfaye ZT, Nedi T. Potential drug-drug interactions in inpatients treated at the Internal medicine ward of Tikur Anbessa Specialized Hospital. Drug Healthc Patient Saf 2017; 9: 71-6. https://doi.org/10.2147/DHPS.S126336##Thakkar KB, Jain MM, Billa G, Joshi A, Khobragade AA. A Drug utilization study of psychotropic drugs prescribed in the psychiatry outpatient department of a tertiary care hospital. J Clin Diagn Res 2013; 7: 2759-64. https://doi.org/10.7860/JCDR/2013/6760.3885##Tripathi KD. Essentials of Medical Pharmacology. 8th Edition. New Delhi: Jaypee Brothers; 2013. Chapter 32, Drugs Used in Mental Illness: Antipsychotic and Antimanic Drugs; p.462-80. https://doi.org/10.5005/jp/books/12021_34## ##

The impact of mild and short-term social stress on urinary levels of T3 and iodine in students of elementary schools 2 2 Introduction: Stress is a determinant factor in thyroid gland functions. A decrease in iodine concentration and thyroid hormones impairs cognitive functions in students. The responsiveness of thyroid hormones to stresses depends on many factors such as the intensity and duration of a particular stressor. This study aimed to examine the effect of mild and short-term social stress on heart rate (HR), blood pressure (BP), triiodothyronine (T3) and iodine concentrations of urine in students. Methods: This controlled before-after study was conducted on 200 students aged 9-12 years (100 girls and 100 boys). The HR and BP of the students were measured and their urine samples were collected before and after the intervention in both stressed and control students. To induce stress, the students were asked to read aloud a text from their own book in front of some audience. Results: In a mixed sample of girls and boys, a significant effect of stress was detected on BP and HR. There was no significant association between the stress and urinary level of T3 and iodine neither in girls nor in boys (and mixed sample). In girls, HR significantly increased in the stressed group while there was no significant connection between stress and BP. In boys, there was a significant difference between stress and control groups in terms of systolic and diastolic BP, but not the HR. Conclusion: Although the stress had a significant sex-specific impact on HR and BP, urinary levels of T3 and iodine were not affected in elementary students. 214 222 2020/09/182021/04/132020/09/272020/03/30 1399/1/11 2021/01/312021/07/262021/01/172021/01/31 1399/11/12 Sakineh Nouri Saeidlou Sakineh Nouri Saeidlou Food and Beverages Safety Research Center, Urmia University of Medical Science, Urmia, Iran Iran Ehsan Saboory Ehsan Saboory Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran Iran saboory@zums.ac.ir Leila Derafshpour Leila Derafshpour Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran Iran Sima Masudi Sima Masudi Department of Biostatistics and Epidemiology, School of Medicine, Urmia University of Medical Science, Urmia, Iran Iran Zafar Gholinejad Zafar Gholinejad Department of Biochemistry, School of Medicine, Urmia University of Medical Science, Urmia, Iran Iran Yousef Rasmi Yousef Rasmi Department of Biochemistry, School of Medicine, Urmia University of Medical Science, Urmia, Iran Iran Blood pressure Elementary schools Iodine Metabolic adjustments Social stress T3. Angermayr L, Clar C. Iodine supplementation for preventing iodine deficiency disorders in children. Cochrane Database Syst Rev 2004: Cd003819.##Armario A, Castellanos J, Balasch J. Effect of acute and chronic psychogenic stress on corticoadrenal and pituitary-thyroid hormones in male rats. Horm Res Paediatr 1984; 20: 241-245.##Baumgartner A. Thyroxine and the treatment of affective disorders: An overview of the results of basic and clinical research. Int J Neuropsychopharmacol 2000; 3: 149-165.##Bianco AC, Nunes MT, Hell NS, Maciel RM. The role of glucocorticoids in the stress-induced reduction of extrathyroidal 3, 5, 3′-triiodothyronine generation in rats. Endocrinology 1987; 120: 1033-1038.##Boelen A, Wiersinga WM, Fliers E. Fasting-induced changes in the hypothalamus–pituitary–thyroid axis. Thyroid 2008; 18: 123-129.##Bogoroch R, Timiras P. The response of the thyroid gland of the rat to severe stress. Endocrinology 1951; 49: 548-556.##Brindle RC, Ginty AT, Phillips AC, Carroll D. A tale of two mechanisms: A meta-analytic approach toward understanding the autonomic basis of cardiovascular reactivity to acute psychological stress. Psychophysiology 2014; 51: 964-76.##Chorpita BF, Barlow DH. The development of anxiety: The role of control in the early environment. Psychol Bull 1998; 124: 3-21.##Crockford SJ. Thyroid rhythm phenotypes and hominid evolution: A new paradigm implicates pulsatile hormone secretion in speciation and adaptation changes. Comp Biochem Physiol A Mol Integr Physiol 2003; 135: 105-29.##Dellovade TL, Zhu YS, Krey L, Pfaff DW. Thyroid hormone and estrogen interact to regulate behavior. Proc Natl Acad Sci U S A 1996; 93: 12581-6.##Dunn JT, Crutchfield HE, Gutekunst R, Dunn AD. Two simple methods for measuring iodine in urine. Thyroid 1993; 3: 119-23.##Etches R, John T, Gibbins AV. Behavioural, physiological, neuroendocrine and molecular responses to heat stress. USA: CABI, 2008.##Gholami M, Saboory E. Neonatal morphine exposure induces age-dependent alterations in pentylenetetrazole-induced epileptic behaviors in prepubertal rats. developmental psychobiology 2013; 55: 881-887.##Gholipoor P, Saboory E, Ghazavi A, Kiyani A, Roshan-Milani S, Mohammadi S, et al. Prenatal stress potentiates febrile seizure and leads to long-lasting increase in cortisol blood levels in children under 2 years old. Epilepsy Behav 2017; 72: 22-27.##Gordon RC, Rose MC, Skeaff SA, Gray AR, Morgan KM, Ruffman T. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr 2009; 90: 1264-71.##Hangalapura B, Nieuwland M, Buyse J, Kemp B, Parmentier H. Effect of duration of cold stress on plasma adrenal and thyroid hormone levels and immune responses in chicken lines divergently selected for antibody responses. Poultry science 2004; 83: 1644-1649.##Kamarck TW, Schwartz JE, Shiffman S, Muldoon MF, Sutton-Tyrrell K, Janicki DL. Psychosocial stress and cardiovascular risk: What is the role of daily experience? J Pers 2005; 73: 1749-74.##Kondo K, Harbuz MS, Levy A, Lightman SL. Inhibition of the hypothalamic-pituitary-thyroid axis in response to lipopolysaccharide is independent of changes in circulating corticosteroids. Neuroimmunomodulation 1997; 4: 188-94.##Kudielka BM, Buske-Kirschbaum A, Hellhammer DH, Kirschbaum C. Differential heart rate reactivity and recovery after psychosocial stress (tsst) in healthy children, younger adults, and elderly adults: The impact of age and gender. Int J Behav Med 2004; 11: 116-121.##Kyriacou A, McLaughlin J, Syed AA. Thyroid disorders and gastrointestinal and liver dysfunction: A state of the art review. Eur J Intern Med 2015; 26: 563-71.##Magomeddibirova Z, Tazutdinova G, Magomedkhanova U, Kurbanova A, Asadulaeva F, Abdurakhmanova A. The influence of adequate iodine intake on the level of stress resistance and the capacity of short-term memory in schoolchildren. J Pharm Sci Res 2017; 9: 904-909.##Matthews KA, Stoney CM. Influences of sex and age on cardiovascular responses during stress. Psychosom Med 1988; 50: 46-56.##McEwen BS. Allostasis and allostatic load: Implications for neuropsychopharmacology. Neuropsychopharmacology 2000; 22: 108-24.##Melse-Boonstra A, Jaiswal N. Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development. Best Pract Res Clin Endocrinol Metab 2010; 24: 29-38.##Nadolnik L. Role of glucocorticoids in regulation of iodine metabolism in thyroid gland: Effects of hyper‐and hypocorticism. Glucocorticoids ‐ new recognition of our familiar friend, dr. Xiaoxiao qian: InTech, 2012.##Saboory E, Mohammadi S, Dindarian S, Mohammadi H. Prenatal stress and elevated seizure susceptibility: Molecular inheritable changes. Epilepsy Behav 2019; 96: 122-131.##Samuels MH, McDaniel PA. Thyrotropin levels during hydrocortisone infusions that mimic fasting-induced cortisol elevations: A clinical research center study. J Clin Endocrinol Metab 1997; 82: 3700-4.##Sephton S, Sapolsky R, Kraemer H, Spiegel D. Early mortality in metastatic breast cancer patients with absent or abnormal diurnal cortisol rhythms. J Natl Cancer Inst 2000; 92: 994-1000.##Servatius RJ, Natelson BH, Moldow R, Pogach L, Brennan FX, Ottenweller JE. Persistent neuroendocrine changes in multiple hormonal axes after a single or repeated stressor exposures. Stress 2000; 3: 263-74.##Smith TW, Birmingham W, Uchino BN. Evaluative threat and ambulatory blood pressure: Cardiovascular effects of social stress in daily experience. Health Psychology 2012; 31: 763.##Turakulov Y, Burikhanov RB, Patkhitdinov PP, Myslitskaya AI. Influence of immobilization stress on the level of secretion of thyroid hormones. Neurosci Behav Physiol 1994; 24: 462-4.##van den Briel T, West CE, Bleichrodt N, van de Vijver FJ, Ategbo EA, Hautvast JG. Improved iodine status is associated with improved mental performance of schoolchildren in benin. Am J Clin Nutr 2000; 72: 1179-85.##WHO. Assessment of iodine deficiency disorders and monitoring their elimination: A guide for programme managers: Geneva: World Health Organization, 2001.##Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on body function: A review. EXCLI journal 2017; 16: 1057.##Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: A review. Am J Clin Nutr 2009; 89: 668s-72s.##Zimmermann MB, Andersson M. Assessment of iodine nutrition in populations: Past, present, and future. Nutr Rev 2012; 70: 553-70.## ##

High-dose fluoxetine improved long-term potentiation of the hippocampal dentate gyrus in male rats 2 2 Introduction: Paradoxical data have been reported regarding the effects of fluoxetine on different types of learning and memory. Hippocampus-dependent memory is mediated by long-term potentiation (LTP). Here, we evaluated the effects of acute administration of fluoxetine on LTP induction in the hippocampal dentate gyrus of intact rats. Methods: Eighteen rats were divided into three groups: the control group received saline 15min before high-frequency stimulation (HFS) and the fluoxetine groups were treated with fluoxetine (2 or 10mg/kg), 15min before HFS. The rats were anesthetized with urethane and put in a stereotaxic system for surgery, electrode implantation and field recording. After ensuring a steady-state baseline response, a single intraperitoneal injection of saline or fluoxetine (2 or 10mg/kg) was done. Next, population spike amplitude, excitatory postsynaptic potential (EPSP) slope, and paired-pulse stimuli (to determine recurrent inhibitory interneuron) were measured in the hippocampal dentate gyrus in three groups. Results: The results showed that population spike amplitude markedly increased in the fluoxetine (2 and 10mg/kg) group than in the saline group. Also, EPSP slope induction in the fluoxetine (10mg/kg) group showed an increase, 60min after HFS compared with the control group. Fluoxetine did not significantly affect recurrent inhibition. Conclusion: These results indicated that the acute administration of high-dose fluoxetine (10mg/kg) can induce LTP. Thus, fluoxetine can be considered as a memory enhancer in intact rats. 223 230 2020/09/182021/04/132020/09/272020/03/302020/10/21 1399/7/30 2021/01/312021/07/262021/01/172021/01/312021/01/25 1399/11/6 Siamak Shahidi Siamak Shahidi Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Iran Leila Rabiee Leila Rabiee Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Iran Alireza Komaki Alireza Komaki Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Iran Reihaneh Sadeghian Reihaneh Sadeghian Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran Iran sadeghian.r@skums.ac.ir Fluoxetine Selective serotonin reuptake inhibitors Long-term potentiation Hippocampus. Bacqué-Cazenave J, Bharatiya R, Barrière G, Delbecque JP, Bouguiyoud N, Di Giovanni G, et al. Serotonin in animal cognition and behavior. Int J Mol Sci 2020; 21: 1649. https://doi.org/10.3390/ijms21051649##Bath KG, Jing DQ, Dincheva I, Neeb CC, Pattwell SS, Chao MV, et al. BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity. Neuropsychopharmacology 2012; 37: 1297-304. https://doi.org/10.1038/npp.2011.318##Baudry M. Long-term Potentiation (Hippocampus). In: Smelser NJ, Baltes PB, editors. International encyclopedia of the social & behavioral sciences. Oxford: Pergamon, 2001, p. 9081-3. https://doi.org/10.1016/B0-08-043076-7/03435-5##Catapano LA, Manji HK. G protein-coupled receptors in major psychiatric disorders. Biochim Biophys Acta Biomembr 2007; 1768: 976-93. https://doi.org/10.1016/j.bbamem.2006.09.025##Cooke JD, Cavender HM, Lima HK, Grover LM. Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus. Psychopharmacology 2014; 231: 4429-41. https://doi.org/10.1007/s00213-014-3587-1##Cooke JD, Grover LM, Spangler PR. Venlafaxine treatment stimulates expression of brain-derived neurotrophic factor protein in frontal cortex and inhibits long-term potentiation in hippocampus. Neuroscience 2009; 162: 1411-9. https://doi.org/10.1016/j.neuroscience.2009.05.037##Dringenberg HC. The history of long-term potentiation as a memory mechanism: controversies, confirmation, and some lessons to remember. Hippocampus 2020; 30: 987-1012. https://doi.org/10.1002/hipo.23213##Hamilton TJ, Kwan GT, Gallup J, Tresguerres M. Acute fluoxetine exposure alters crab anxiety-like behaviour, but not aggressiveness. Sci Rep 2016; 6: 1-6. https://doi.org/10.1038/srep19850##Karamian R, Komaki A, Salehi I, Tahmasebi L, Komaki H, Shahidi S, et al. Vitamin C reverses lead-induced deficits in hippocampal synaptic plasticity in rats. Brain Res Bull 2015; 116: 7-15. https://doi.org/10.1016/j.brainresbull.2015.05.004##Keith JR, Wu Y, Epp JR, Sutherland RJ. Fluoxetine and the dentate gyrus: memory, recovery of function, and electrophysiology. Behav Pharmacol 2007; 18: 521-31. https://doi.org/10.1097/FBP.0b013e3282d28f83##Kobayashi K, Ikeda Y, Haneda E, Suzuki H. Chronic fluoxetine bidirectionally modulates potentiating effects of serotonin on the hippocampal mossy fiber synaptic transmission. J Neurosci 2008; 28: 6272-80. https://doi.org/10.1523/JNEUROSCI.1656-08.2008##Lashgari R, Khakpour-Taleghani B, Motamedi F, Shahidi S. Effects of reversible inactivation of locus coeruleus on long-term potentiation in perforant path-DG synapses in rats. Neurobiol Learn Mem 2008; 90: 309-16. https://doi.org/10.1016/j.nlm.2008.05.012##Lynch MA. Long-term potentiation and memory. Physiol Rev 2004; 84: 87-136. https://doi.org/10.1152/physrev.00014.2003##Marken PA, Munro JS. Selecting a selective serotonin reuptake inhibitor: clinically important distinguishing features. Prim Care Companion J Clin Psychiatry 2000; 2: 205-210. https://doi.org/10.4088/PCC.v02n0602##Marwari S, Dawe G. (R)-fluoxetine enhances cognitive flexibility and hippocampal cell proliferation in mice. J Psychopharmacol 2018; 32: 441-57. https://doi.org/10.1177/0269881118754733##Meneses A, Hong E. Effect of fluoxetine on learning and memory involves multiple 5-HT systems. Pharmacol Biochem Behav 1995; 52: 341-6. https://doi.org/10.1016/0091-3057(95)00102-3##Mnie-Filali O, El Mansari M, Espana A, Sànchez C, Haddjeri N. Allosteric modulation of the effects of the 5-HT reuptake inhibitor escitalopram on the rat hippocampal synaptic plasticity. Neurosci lett 2006; 395: 23-7. https://doi.org/10.1016/j.neulet.2005.10.044##Molaei A, Hatami H, Dehghan G, Sadeghian R, Khajehnasiri N. Synergistic effects of quercetin and regular exercise on the recovery of spatial memory and reduction of parameters of oxidative stress in animal model of Alzheimer’s disease. Excli J 2020; 19: 596-612.##Ohashi S, Matsumoto M, Otani H, Mori K, Togashi H, Ueno K, et al. Changes in synaptic plasticity in the rat hippocampo-medial prefrontal cortex pathway induced by repeated treatments with fluvoxamine. Brain Res 2002; 949: 131-8. https://doi.org/10.1016/S0006-8993(02)02973-6##Ohashi S, Togashi H, Matsumoto M, Mori K, Ueno K, Yoshioka M. Changes in synaptic properties in cortical-limbic communications induced by repeated treatments with fluvoxamine in rats. J Pharmacol Sci 2003; 92: 100-7. https://doi.org/10.1254/jphs.92.100##Ohira K, Hagihara H, Miwa M, Nakamura K, Miyakawa T. Fluoxetine-induced dematuration of hippocampal neurons and adult cortical neurogenesis in the common marmoset. Mol Brain 2019; 12: 69. https://doi.org/10.1186/s13041-019-0489-5##Pawluski JL, van Donkelaar E, Abrams Z, Houbart V, Fillet M, Steinbusch HW, et al. Fluoxetine dose and administration method differentially affect hippocampal plasticity in adult female rats. Neural Plast 2014; 2014: 123026. https://doi.org/10.1155/2014/123026##Popova D, Castrén E, Taira T. Chronic fluoxetine administration enhances synaptic plasticity and increases functional dynamics in hippocampal CA3-CA1 synapses. Neuropharmacology 2017; 126: 250-6. https://doi.org/10.1016/j.neuropharm.2017.09.003##Reisi P, Sepahvand F, Zarei G, Kamali Dolatabadi L, Haghjooye Javanmard S, Alaei H. Effects of amitriptyline and fluoxetine on synaptic plasticity and TNF-α level at hippocampus of streptozotocin-induced diabetic rats. Physiol Pharmacol 2017; 21: 137-46.##Rubio FJ, Ampuero E, Sandoval R, Toledo J, Pancetti F, Wyneken U. Long-term fluoxetine treatment induces input-specific LTP and LTD impairment and structural plasticity in the CA1 hippocampal subfield. Front Cell Neurosci 2013; 7: 66. https://doi.org/10.3389/fncel.2013.00066##Sadeghian R, Fereidoni M, Soukhtanloo M, Azizi-Malekabadi H, Hosseini M. Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol. Arq Neuropsiquiatr 2012; 70: 874-9. https://doi.org/10.1590/S0004-282X2012001100010##Shahidi S, Komaki A, Sadeghian R, Asl SS. Different doses of methamphetamine alter long-term potentiation, level of BDNF and neuronal apoptosis in the hippocampus of reinstated rats. J Physiol Sci 2019a; 69: 409-19. https://doi.org/10.1007/s12576-019-00660-1##Shahidi S, Komaki A, Sadeghian R, Asl SS. Effect of a 5-HT1D receptor agonist on the reinstatement phase of the conditioned place preference test and hippocampal long-term potentiation in methamphetamine-treated rats. Brain Res 2018a; 1698: 151-60. https://doi.org/10.1016/j.brainres.2018.07.030##Shahidi S, Mehrpour O, Sadeghian R, Asl SS, Komaki A. Alteration level of hippocampus BDNF expression and long-term potentiation upon microinjection of BRL15572 hydrochloride in a rat model of methamphetamine relapse. Brain Res Bull 2019b; 148: 18-24. https://doi.org/10.1016/j.brainresbull.2019.03.008##Shahidi S, Sadeghian R, Komaki A, Asl SS. Intracerebroventricular microinjection of the 5-HT1F receptor agonist LY 344864 inhibits methamphetamine conditioned place preference reinstatement in rats. Pharmacol Biochem Behav 2018b; 173: 27-35. https://doi.org/10.1016/j.pbb.2018.08.001##Stäubli U, Xu FB. Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat. 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The effect of swimming exercise on thyroid function, spatial memory and anxiety in normal and propylthiouracil-induced hypothyroidism in Wistar rats 2 2 Introduction: Swimming exercises improve various nerve growth factors and angiogenesis that encouraged the researchers to investigate the effect of swimming exercises on thyroid function (cyclic adenosine monophosphate [cAMP] and dual oxidase 2 [DUOX2] in free T4 [FT4] secretion), spatial memory, behavior and anxiety on normal Wistar pups and those given with propylthiouracil (PTU). Methods: The subjects of this research were normal Wistar pups and those given 25 ppm PTU from the 1st week until the 12th week of age. Swimming activity was started in 4-weekold pups after acclimatization for 1 week. Swimming exercises were conducted with a load of 1–2% body weight and 30min duration per day, 5 times a week for 8 weeks. The levels of FT4 serum, cAMP and DUOX2 of the thyroid gland homogenate were measured using enzyme-linked immunosorbent assay. The rats’ ability to maintain spatial memory was measured using the Morris water maze and anxiety using the open field maze. Results: The FT4 levels significantly decreased after the administration of 25 ppm PTU for 3 weeks and it was much more decreased after 12 weeks administration. The administration of 25 ppm PTU for 12 weeks reduced the cAMP levels, increased DUOX2 and reduced the spatial memory skills and exploration behavior of rats. Swimming exercise increased and normalized these parameters. Conclusion: Swimming exercises for 8 weeks improve thyroid function, learning ability and spatial memory of normal and PTU-induced hypothyroid Wistar rats. 231 241 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/25 1399/4/5 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/13 1399/9/23 Zulkhah Noor Zulkhah Noor Physiology Department, Faculty of Medicine and Health Sciences, Muhammadiyah University of Yogyakarta, Yogyakarta, Indonesia Indonesia capa.journal116@klinikjurnal.com Denny Agustiningsih Denny Agustiningsih Physiology Department, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia Indonesia Marsetyawan HNE Soesatyo Marsetyawan HNE Soesatyo Histology Department, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia Indonesia Sri Kadarsih Soejono Sri Kadarsih Soejono Physiology Department, Faculty of Medicine and Health Sciences, Muhammadiyah University of Yogyakarta, Yogyakarta, Indonesia Indonesia Anxiety cAMP FT4 Propylthiouracil Spatial memory. 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Topical formulation of tranilast improves hypertrophic scar in a rat model 2 2 Introduction: Hypertrophic scars are dermal complication that may lead to considerable morbidity. There is an intense medical need for novel therapies for this disease. Tranilast is an anti-allergic agent that clinically used for the treatment of keloids and hypertrophic scars. In this study, we aimed to evaluate the effect of tranilast 0.5% topical formulation on hypertrophic scars resulted by burn injury in rats. Methods: Burn wounds were inflicted on the skin area of the backs of all rats, following that the scars are created, treatment started and continued for 28 days. Animals were divided into two groups (n=8): the control scar group, which received a placebo and the treatment group that received 0.5% tranilast gel. After this period, skin biopsies were collected from each group for the following analyses. The tissue samples were analyzed by hematoxylin-eosin, Masson’s trichrome staining and qRT-PCR. Results: Histologically, topical tranilast reduced hypertrophic scar signs as compared to placebo. Tranilast treatment also resulted in a reduction in type I and III collagen, transforming growth factor-beta1, Smad2 and vascular endothelial growth factor , and increased Smad7 mRNA expression in the skin scar site. Conclusion: These findings showed that the 0.5% tranilast topical gel could be effective in the treatment of hypertrophic scars in a rat experiment. 242 250 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/252020/08/5 1399/5/15 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/132020/12/13 1399/9/23 Sara Darakhshan Sara Darakhshan Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Fereshteh Bagheri Fereshteh Bagheri Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Seyran Kakabaraei Seyran Kakabaraei Department of Anatomical Sciences & Cell Biology, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Reza Tahvilian Reza Tahvilian Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran rtahvilian@kums.ac.ir Tranilast Hypertrophic scar Wound healing Topical formulation. Bonnet F, Cao Z, Cooper ME, Cox AJ, Kelly DJ, Gilbert RE. Tranilast attenuates vascular hypertrophy, matrix accumulation and growth factor overexpression in experimental diabetes. Diabetes Metab 2003; 29: 386-92. https://doi.org/10.1016/S1262-3636(07)70049-6##Borena BM, Martens A, Broeckx SY, Meyer E, Chiers K, Duchateau L, et al. Regenerative skin wound healing in mammals: state-of-the-art on growth factor and stem cell based treatments. Cell Physiol Biochem 2015; 36: 1-23. https://doi.org/10.1159/000374049 ##Brett EA, Duscher D. Scar treatment and prevention: know thine enemy. In: Regenerative Medicine and plastic surgery. Springer, Cham. 2019, pp. 16-26. https://doi.org/10.1007/978-3-030-19962-3_2 ##Chen MA, Davidson TM. Scar management: prevention and treatment strategies. Curr Opin Otolaryngol Head Neck Surg 2005; 13: 242-7. https://doi.org/10.1097/01.moo.0000170525.74264.f8 ##Cuttle L, Kempf M, Phillips GE, Mill J, Hayes MT, Fraser JF, et al. A porcine deep dermal partial thickness burn model with hypertrophic scarring. Burns 2006; 32: 806-20. https://doi.org/10.1016/j.burns.2006.02.023 ##Darakhshan S, Pour AB. Tranilast: a review of its therapeutic applications. Pharmacol Res 2015; 91: 15-28. https://doi.org/10.1016/j.phrs.2014.10.009 ##Goto Y, Tsuchiya O, Nishiyama M, Suzawa H, Miyata H. Studies on the metabolic fate of tranilast in rats and mice. J Clin Report 1991; 25: 69-74. ##Infanger M, Schmidt O, Kossmehl P, Grad S, Ertel W, Grimm D. Vascular endothelial growth factor serum level is strongly enhanced after burn injury and correlated with local and general tissue edema. Burns 2004; 30: 305-11. https://doi.org/10.1016/j.burns.2003.12.006 ##Isaji M, Miyata H, Ajisawa Y, Takehana Y, Yoshimura N. Tranilast inhibits the proliferation, chemotaxis and tube formation of human microvascular endothelial cells in vitro and angiogenesis in vivo. Br J Pharmacol 1997; 122: 1061-6. https://doi.org/10.1038/sj.bjp.0701493 ##Khiljee S, Rehman N, Sarfraz M, Montazeri H, Lbenberg R, Khiljee T. In vitro release of indian penny wort, walnut, and turmeric from topical preparations using two different types of membranes. Dissolufion Technol 2010; 17: 27-32. https://doi.org/10.14227/DT170410P27 ##Koese O, Waseem A. Keloids and hypertrophic scars: are they two different sides of the same coin? Dermatol Surg 2008; 34: 336-46. https://doi.org/10.1111/j.1524-4725.2007.34067.x ##Kogure F, Ishizaki M, Saiga T. Long-term clinical study of tranilast ophthalmic solution on vernal conjunctivitis. J Clin Ther Med 1993; 9: 429-41. ##Kohavi L, Sprecher E, Zur E, Artzi O. The effect of tranilast 8% liposomal gel versus placebo on post-cesarean surgical scars: a prospective double-blind split-scar study. Dermatol Surg 2017; 43: 1157-63. https://doi.org/10.1097/DSS.0000000000001140 ##Leask A. Potential therapeutic targets for cardiac fibrosis: TGFβ, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res 2010; 106: 1675-80. https://doi.org/10.1161/CIRCRESAHA.110.217737 ##Lichtman MK, Otero-Vinas M, Falanga V. Transforming growth factor beta (TGF-β) isoforms in wound healing and fibrosis. Wound Repair Regen 2016; 24: 215-22. https://doi.org/10.1111/wrr.12398 ##Liu Z, Lu CL, Cui LP, Hu YL, Yu Q, Jiang Y, et al. MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4. Arch Dermatol Res 2012; 304: 195-202. https://doi.org/10.1007/s00403-011-1178-0 ##Marshall CD, Hu MS, Leavitt T, Barnes LA, Lorenz HP, Longaker MT. Cutaneous scarring: basic science, current treatments, and future directions. Adv Skin Wound Care 2018; 7: 29-45. https://doi.org/10.1089/wound.2016.0696 ##Martin D, Umraw N, Gomez M, Cartotto R. 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Protective effects of date palm pollen extract on gentamicin-induced hepatotoxicity 2 2 Introduction: Gentamicin, as an aminoglycoside antibiotic, is used to treat gram-negative bacterial infections. But despite its beneficial effects, gentamicin has side effects such as hepatotoxicity. Therefore, the aim of the present study was to investigate the protective effect of date palm pollen (DPP) hydroalcoholic extract against gentamicin-induced hepatotoxicity in rats. Methods: In present study the animals were divided into 5 groups, including control, sham, gentamicin and the two groups of gentamicin plus DPP extract at 200mg/kg and 400mg/kg. The plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes were measured to assess hepatic functional damages. Also, antioxidant enzymes activity including catalase (CAT) and superoxide dismutase (SOD) as well as total antioxidant capacity (FRAP) of the liver tissue sample were measured. Further, a tissue sample was fixed in 10% formaldehyde for hematoxylin and eosin staining and histopathological study. In the end of experiment, the animals were euthanized by deep anesthesia. Results: Gentamicin significantly increased the levels of plasma AST and ALT enzymes, caused histopathological damages, decreased CAT and SOD enzymes as well as FRAP in the liver tissue in comparison to the sham group. The concomitant administration of DPP hydroalcoholic extract and gentamicin with both examined doses could relatively improve these parameters, so that some parameters have not significant difference with the sham group. Conclusion: It can be concluded that the hydroalcoholic extract of DPP reduces histopathological damages, oxidative stress as well as hepatic enzymes following their increase by gentamicin. 251 260 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/252020/08/52020/08/2 1399/5/12 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/132020/12/132020/12/13 1399/9/23 Zeynab Mohamadi Yarijani Zeynab Mohamadi Yarijani Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Seyed Hamid Madani Seyed Hamid Madani Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Saeed Changizi-Ashtiyani Saeed Changizi-Ashtiyani Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Iran Houshang Najafi Houshang Najafi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran hnajafi@kums.ac.ir Gentamicin Date palm pollen Hepatotoxicity Oxidative stress Histopathological damages. Abbas FA, Ateya AM. Estradiol, esteriol, estrone and novel flavonoids from date palm pollen. Aust J Basic Appl Sci 2011; 5: 606-14.##Ademiluyi AO, Oboh G, Owoloye TR, Agbebi OJ. Modulatory effects of dietary inclusion of garlic (Allium sativum) on gentamycin-induced hepatotoxicity and oxidative stress in rats. Asian Pac J Trop Biomed 2013; 3: 470-5. https://doi.org/10.1016/S2221-1691(13)60098-2##Benzie IF, Strain JJ. Ferric reducing/antioxidant power assay: Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999; 299: 15-27. https://doi.org/10.1016/S0076-6879(99)99005-5##Daoud A, Mnafgui K, Turki M, Jmal S, Ayadi F, ElFeki A, et al. Cardiopreventive effect of ethanolic extract of Date Palm Pollen against isoproterenol induced myocardial infarction in rats through the inhibition of the angiotensin-converting enzyme. Exp Toxicol Pathol 2017; 69: 656-65. https://doi.org/10.1016/j.etp.2017.06.004 ##Doi K, Rabb H. Impact of acute kidney injury on distant organ function: recent findings and potential therapeutic targets. Kidney Int 2016; 89: 555-64. https://doi.org/10.1016/j.kint.2015.11.019##Elberry AA, Mufti ST, Al-Maghrabi JA, Abdel-Sattar EA, Ashour OM, Ghareib SA, et al. Anti-inflammatory and antiproliferative activities of date palm pollen (Phoenix dactylifera) on experimentally-induced atypical prostatic hyperplasia in rats. J Inflamm 2011; 8: 1-3. https://doi.org/10.1186/1476-9255-8-40##El-Kashlan AM, Nooh MM, Hassan WA, Risk SM. Therapeutic potential of date palm pollen for testicular dysfunction induced by thyroid disorders in male rats. PLoS One 2015; 10: e0139493. https://doi.org/10.1371/journal.pone.0139493##El-Neweshy M, El-Maddawy Z, El-Sayed YJA. Therapeutic effects of date palm (P hoenix dactylifera L.) pollen extract on cadmium-induced testicular toxicity. Andrologia 2013; 45: 369-78. https://doi.org/10.1111/and.12025##Galaly SR, Ahmed OM, Mahmoud AM. Thymoquinone and curcumin prevent gentamicin-induced liver injury by attenuating oxidative stress, inflammation and apoptosis. J Physiol Pharmacol 2014; 65: 823-32.##Gardner DS, Brot SD, Dunford LJ, Roma LG, Welham SJM, Fallman R, et al. Remote effects of acute kidney injury in a porcine model. Am J Physiol Renal Physiol 2016; 310: F259-71. https://doi.org/10.1152/ajprenal.00389.2015##Hafazeh L, Changizi-Ashtiyani S, Jalali-Mashayekhi F, Rahjo T, Najafi H, Babaei S. The therapeutic effect of Centella asiatica hydroalcoholic extract on gentamicin-induced nephrotoxicity. Physiol Pharmacol 2019; 23: 215-23.##Hassan HM. Chemical composition and nutritional value of palm pollen grains. Glob J Biotech Biochem 2011; 6: 1-7.##Iftikhar S, Ahmad M, Aslam HM, Saeed T, Arfat Y. Evaluation of spermatogenesis in prepubertal albino rats with date palm pollen supplement. Afr J Pharm Pharmacol 2014; 8: 59-65. https://doi.org/10.5897/AJPP2013.3662##Katary M, Salahuddin A. Ameliorative effect of gossypin against gentamicin-induced nephrotoxicity in rats. Life Sci 2017; 176: 75-81. https://doi.org/10.1016/j.lfs.2017.03.009##Khaksari M, Esmaili S, Abedloo R, Khastar H. Palmatine ameliorates nephrotoxicity and hepatotoxicity induced by gentamicin in rats. Arch Physiol Biochem 2019; 26: 1-6. https://doi.org/10.1080/13813455.2019.1633354##Khan MR, Badar I, Siddiquah A. Prevention of hepatorenal toxicity with sonchus asper in gentamicin treated rats. BMC Complement Altern Med 2011; 11: 1-9. https://doi.org/10.1186/1472-6882-11-113##Lee SA, Cozzi M, Bush EL, Rabb H. Distant organ dysfunction in acute kidney injury: a review. Am J Kidney Dis 2018; 72: 846-56. https://doi.org/10.1053/j.ajkd.2018.03.028##Mahi-Birjand M, Yaghoubi S, Abdollahpour-Alitappeh M, Keshtkaran Z, Bagheri N, Pirouzi A, et al. Protective effects of pharmacological agents against aminoglycoside-induced nephrotoxicity: a systematic review. Expert Opin Drug Saf 2020; 19: 167-86. https://doi.org/10.1080/14740338.2020.1712357##Mahmoud AM, Ahmed OM, Galaly SR. Thymoquinone and curcumin attenuate gentamicin-induced renal oxidative stress, inflammation and apoptosis in rats. EXCLI J 2014; 13: 98-110.##Mahmoud YI. Kiwi fruit (Actinidia deliciosa) ameliorates gentamicin-induced nephrotoxicity in albino mice via the activation of Nrf2 and the inhibition of NF-κB (Kiwi & gentamicin-induced nephrotoxicity). Biomed Pharmacother 2017; 94: 206-18. https://doi.org/10.1016/j.biopha.2017.07.079##Manikandan R, Beulaja M, Thiagarajan R, Priyadarsini A, Saravanan R, Arumugam M. Ameliorative effects of curcumin against renal injuries mediated by inducible nitric oxide synthase and nuclear factor kappa B during gentamicin-induced toxicity in Wistar rats. Eu J Pharmacol 2011; 670: 578-85. https://doi.org/10.1016/j.ejphar.2011.08.037##Martinez-Salgado C, Eleno N, Morales AI, Perez-Barriocanal F, Arevalo M, Lopez-Novoa JM. Gentamicin treatment induces simultaneous mesangial proliferation and apoptosis in rats. Kidney Int 2004; 65: 2161-71. https://doi.org/10.1111/j.1523-1755.2004.00642.x##Metwaly MS, Dkhil MA, Al-Quraishy S. Anti-coccidial and anti-apoptotic activities of palm pollen grains on Eimeria papillata-induced infection in mice. Biologia 2014: 69: 254-9. https://doi.org/10.2478/s11756-013-0297-9##Mohammadi M, Najafi H, Yarijani ZM, Vaezi G, Hojati V. Piperine pretreatment attenuates renal ischemia-reperfusion induced liver injury. Heliyon 2019; 5: e02180. https://doi.org/10.1016/j.heliyon.2019.e02180##Mohamed NA, Ahmed OM, Hozayen WG, Ahmed MA. Ameliorative effects of bee pollen and date palm pollen on the glycemic state and male sexual dysfunctions in streptozotocin-Induced diabetic wistar rats. 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Antioxidant activity, phenolic and flavonoid content of Lawsonia inermis and Haplophyllum vermiculare 2 2 Introduction: Continuous exposure of oxidants to the skin may disrupt the antioxidant balance and leads to inflammatory skin diseases (ISD). The aim of the present study was to compare the antioxidant activity, phenolic and flavonoid content of two traditionally used plants in ISD, Lawsonia inermis and Haplophyllum vermiculare. Methods: The hydroethanolic extract of the plants was prepared by maceration. Phenolic and flavonoid content of the extracts was measured respectively with Folin-Ciocateu and aluminum chloride methods. The monovalent reducing power and radical scavenging activity were also evaluated respectively by ferric reducing antioxidant power and 2,2-diphenyl-1-picryl-hydrazyl methods. Results: The reducing power of Lawsonia inermis (862.89±32.23 μmolFe2+/g) was significantly higher than Haplophyllum vermiculare extract (765.52±29.39 μmolFe2+/g). The radical scavenging activity of Lawsonia inermis extract at a concentration of 1000μg/ml (%65.72±0.77) was also significantly higher than Haplophyllum vermiculare (%36.34±2.52). The higher antioxidant activity of Lawsonia inermis is probably due to its higher phenolic (96.76±3.34μg GAE/mg) and flavonoid content (197.69±5.76μg QE/mg). Conclusion: Henna leaves had higher antioxidant activity, phenolic and flavonoid content compared to aerial parts of Haplophyllum vermiculare, and may be more effective in improving oxidative stress, prevention and treatment of ISD. 261 269 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/252020/08/52020/08/22020/06/17 1399/3/28 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/132020/12/132020/12/132020/12/13 1399/9/23 Alireza Moulazadeh Alireza Moulazadeh Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran Seyyed Amin Kouhpayeh Seyyed Amin Kouhpayeh Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran Razieh Ranjbar Razieh Ranjbar Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran Amin Dakhili Ardestani Amin Dakhili Ardestani Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran Iran Maryam Hekmat Maryam Hekmat Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran Iran Sara Azarnia Sara Azarnia Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran s.azarnia@fums.ac.ir Sohrab Najafipour Sohrab Najafipour Medicinal Plant Research Center, Fasa University of Medical Sciences, Fasa, Iran Iran najafipour@fums.ac.ir Lawsonia inermis Haplophyllum vermiculare Antioxidative activity Skin disease Inflammation. Al-Snafi AE. Pharmacological importance of Haplophyllum species grown in Iraq-A review. IOSR J Pharm 2018; 8: 54-62.##Al-Snafi AE. A review on Lawsonia inermis: a potential medicinal plant. Int J Curr Pharm Res 2019; 11: 1-13. https://doi.org/10.22159/ijcpr.2019v11i5.35695 ##Al-Sowayan NS, Mousa HM. Ameliorative effect of olive leaf extract on carbon tetrachloride-induced nephrotoxicity in rats. Life Sci J 2014; 11: 238-42.##Amoussa AM, Sanni A, Lagnika L. Antioxidant activity and total phenolic, flavonoid and flavonol contents of the bark extracts of Acacia ataxacantha. J Pharmacogn Phytochem 2015; 4.##Antiga E, Bonciolini V, Volpi W, Del Bianco E, Caproni M. Oral curcumin (Meriva) is effective as an adjuvant treatment and is able to reduce IL-22 serum levels in patients with psoriasis vulgaris. BioMed Res Int 2015; 2015. https://doi.org/10.1155/2015/283634##Ayyobi N, Fattahi M. 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The protective effects of apigenin on OLN-93 cellular model of cerebral stroke 2 2 Introduction: Cerebral stroke is known to be the third most common cause of death in the world. To study pathophysiology and effects of the therapeutic agents on stroke, the cellular model of stroke recently was used more. ONL-93, oligodendrocyte like cell, is known as an appropriate model to study the role of glial cells in stroke. Apigenin is a flavonoid that has neuroprotective and neurogenic effects; therefore, the purpose of this study was to investigate the role of apigenin flavonoid on the OLN-93 cell line in terms of oxygen and glucose deprivation in the cellular stroke model. Methods: The cells were divided into experimental, negative and positive control groups. Then, MTT, reactive oxygen species (ROS), annexin and propidium iodide as well as Western blotting assays were performed to evaluate the viability and apoptosis. Results: The results showed that there was a significant increase in the number of live cells following administration of 1μM of apigenin in experimental groups and also, there was a significant difference in the number of live cells between two doses of 1μM and 0.75μM of the apigenin. The amount of ROS produced at a concentration of 1μM apigenin was a significant decrease compared to the positive control group and apoptotic cells also decreased significantly. The results for the expression of P53 protein showed a significant reduction in experimental groups. Conclusion: Based on our results, apigenin could have beneficial effects through the reduction of P53 and ROS production. 270 278 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/252020/08/52020/08/22020/06/172020/09/9 1399/6/19 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/132020/12/132020/12/132020/12/132020/10/27 1399/8/6 Samira Miraee Samira Miraee Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Iran Mona Farhadi Mona Farhadi Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Iran mona.farhadi@kiau.ac.ir Seyed Behnamedin Jameie Seyed Behnamedin Jameie Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran Shabnam Najafie Shabnam Najafie Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Iran Oxygen and glucose deprivation Apigenin Apoptosis OLN-93 cell line. Balez R, Steiner N, Engel M, Munoz S, Lum J, Wu Y, et al. Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease. Sci Rep 2016; 6: 1-6. https://doi.org/10.1038/srep31450##Caltagirone S, Rossi C, Poggi A, Ranelletti FO, Natali PG, Brunetti M, et al. Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int J Cancer 2000; 87: 595-600. https://doi.org/10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5 ##Duarte S, Arango D, Parihar A, Hamel P, Yasmeen R, Doseff A. Apigenin protects endothelial cells from lipopolysaccharide (LPS)-induced inflammation by decreasing caspase-3 activation and modulating mitochondrial function. Int J Mol Sci 2013; 14: 17664-79. https://doi.org/10.3390/ijms140917664 ##Haghiroalsadat BF, Vahidi AR, Azimzadeh M, Kalantar SM, Bernard F, Hokm EF. Chemical assessment of active ingredients and anti-oxidant effects of trachyspermum copticum’sseeds harvested in yazd province. J Rafsanjan Univ Med Sci Health Serv 2012; 196-206. ##Kim SJ, Jin YH, Kim BS. Prostaglandin E2 produced following infection with Theiler’s virus promotes the pathogenesis of demyelinating disease. PloS One 2017; 12: e0176406 https://doi.org/10.1371/journal.pone.0176406 ##Li ZD, Hu XW, Wang YT, Fang J. Apigenin inhibits proliferation of ovarian cancer A2780 cells through Id1. FEBS letters 2009; 583: 1999-2003. https://doi.org/10.1016/j.febslet.2009.05.013 ##Logan A, Freeman J, Kent B, Pooler J, Creanor S, Vickery J, et al. Standing Practice In Rehabilitation Early after Stroke (SPIRES): a functional standing frame programme (prolonged standing and repeated sit to stand) to improve function and quality of life and reduce neuromuscular impairment in people with severe sub-acute stroke-a protocol for a feasibility randomised controlled trial. Pilot Feasibility Stud 2018; 4: 1-8. https://doi.org/10.1186/s40814-018-0254-z ##Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 2001; 49: 3106-12. https://doi.org/10.1021/jf000892m ##Nabavi SF, Khan H, D’onofrio G, Šamec D, Shirooie S, Dehpour AR, et al. Apigenin as neuroprotective agent: Of mice and men. Pharmacol Res 2018; 128: 359-65. https://doi.org/10.1016/j.phrs.2017.10.008 ##Pang Q, Zhao Y, Chen X, Zhao K, Zhai Q, Tu F. Apigenin protects the brain against ischemia/reperfusion injury via caveolin-1/VEGF in vitro and in vivo. Oxid Med Cell Longev 2018; 2018. https://doi.org/10.1155/2018/7017204 ##Solanki I, Parihar P, Mansuri ML, Parihar MS. Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 2015; 6: 64-72. https://doi.org/10.3945/an.114.007500 ##Solanki I, Parihar P, Parihar MS. Neurodegenerative diseases: from available treatments to prospective herbal therapy. 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Effects of oxygen-glucose deprivation (OGD) on barrier properties and mRNA transcript levels of selected marker proteins in brain endothelial cells/astrocyte co-cultures. PloS One 2019; 14: e0221103. https://doi.org/10.1371/journal.pone.0221103 ##You Y, Joseph C, Wang C, Gupta V, Liu S, Yiannikas C, et al. Demyelination precedes axonal loss in the transneuronal spread of human neurodegenerative disease. Brain 2019; 142: 426-42. https://doi.org/10.1093/brain/awy338 ##Zhang X, Wang G, Gurley EC, Zhou H. Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One 2014; 9: e107072. https://doi.org/10.1371/journal.pone.0107072## ##

Nicotine effects on enzymatic antioxidant defenses in human breast and ovarian cell lines 2 2 Introduction: Nowadays, the prevalence of nicotine abuse among women has increased dramatically. In the current study, we aimed to investigate the effect of nicotine exposure on breast MCF-7 and ovarian OVCAR-3 cell lines for assessing the toxicity of nicotine in the cells of these organs. Methods: The MCF-7 and OVCAR-3 cells were treated with increasing nicotine concentrations ranging from 0 (control), 10-11, 10-8 and 10-6 M for 24h. Effect of nicotine treatments on major antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), cellular levels of glutathione (GSH) and malondialdehyde (MDA) were monitored. Results: We showed that the CAT activity in MCF-7 cells increased only at 10-6 M dose of nicotine. The GPx and GR activity was decreased at 10-8 and 10-6 M of nicotine in MCF-7 cells, but in OVCAR-3 cells, this decrease was significant only at 10-6 M dose of nicotine. Reduced GSH decrease was statistically significant only at 10-8 and 10-6 M of nicotine in MCF-7 cells; otherwise, in OVCAR-3 cells, this decline was significant only at 10-6 M of nicotine. Nicotine at 10-8 and 10-6 M concentration caused a significant increase in MDA levels in MCF-7 cells. Conclusion: This study showed that breast MCF-7 cells are more vulnerable than ovarian OVCAR-3 cells against nicotine-induced oxidative toxicity. 279 287 2020/09/182021/04/132020/09/272020/03/302020/10/212020/06/252020/08/52020/08/22020/06/172020/09/92020/04/1 1399/1/13 2021/01/312021/07/262021/01/172021/01/312021/01/252020/12/132020/12/132020/12/132020/12/132020/10/272020/12/26 1399/10/6 Amir Yarahmadi Amir Yarahmadi Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Iran Neda Mohammadi Neda Mohammadi Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Iran Fatemeh Zal Fatemeh Zal Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Iran Fatemehzal@sums.ac.ir Nicotine Antioxidant enzymes Oxidative stress MCF-7 cells OVCAR-3 cells. Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.##Aghagolzadeh M, Moghaddam A H, Seyedalipour B. 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