32 24765236 Iranian Society of Physiology and Pharmacology 1681 Pharmacokinetics/Dynamics Antimicrobial potential of a gel containing hydrogen peroxide and hyaluronic acid Tadakamadla Jyothi b Boccalari Elisa c Maspero Cinzia d b School of Medicine and Dentistry, Griffith University, Gold Coast, QLD, Australia c Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan; Milan, Italy d Department of Biomedical, Surgical and Dental Sciences, School of Dentistry, University of Milan; Milan, Italy 1 9 2021 25 3 189 192 18 09 2020 31 01 2021 No abstract provided as this is a letter to the editor 
1789 Cell, Stem Cell and Cancer Molecular mechanisms and signaling pathways involved in immunopathological events of COVID-19 Peyvandi Ali Asghar e Niknazar Somayeh f Zare Mehrjerdi Fatemeh g Abbaszadeh Hojjat-Allah h Khoshsirat Shahrokh i Peyvandi Maryam j e Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran f Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran g Neurobiomedical Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran h Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran i Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran j Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 1 9 2021 25 3 193 205 13 04 2021 26 07 2021 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. 1685 Pharmacokinetics/Dynamics 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 Deshmukh Adit k Dabhade Sangeeta l k Department of Pharmacology, B. J. Government Medical College and Sassoon General Hospital, Pune, India l Department of Pharmacology, B. J. Government Medical College and Sassoon General Hospital, Pune, India 1 9 2021 25 3 206 213 27 09 2020 17 01 2021 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. 1598 Others The impact of mild and short-term social stress on urinary levels of T3 and iodine in students of elementary schools Nouri Saeidlou Sakineh m Saboory Ehsan n Derafshpour Leila o Masudi Sima p Gholinejad Zafar Rasmi Yousef m Food and Beverages Safety Research Center, Urmia University of Medical Science, Urmia, Iran n Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran o Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran p Department of Biostatistics and Epidemiology, School of Medicine, Urmia University of Medical Science, Urmia, Iran Department of Biochemistry, School of Medicine, Urmia University of Medical Science, Urmia, Iran Department of Biochemistry, School of Medicine, Urmia University of Medical Science, Urmia, Iran 1 9 2021 25 3 214 222 30 03 2020 31 01 2021 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. 1699 Neurophysiology/Pharmacology High-dose fluoxetine improved long-term potentiation of the hippocampal dentate gyrus in male rats Shahidi Siamak Rabiee Leila Komaki Alireza Sadeghian Reihaneh Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Department of Physiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran 1 9 2021 25 3 223 230 21 10 2020 25 01 2021 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. 1638 Neurophysiology/Pharmacology The effect of swimming exercise on thyroid function, spatial memory and anxiety in normal and propylthiouracil-induced hypothyroidism in Wistar rats Noor Zulkhah Agustiningsih Denny Soesatyo Marsetyawan HNE Soejono Sri Kadarsih Physiology Department, Faculty of Medicine and Health Sciences, Muhammadiyah University of Yogyakarta, Yogyakarta, Indonesia Physiology Department, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia Histology Department, Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia Physiology Department, Faculty of Medicine and Health Sciences, Muhammadiyah University of Yogyakarta, Yogyakarta, Indonesia 1 9 2021 25 3 231 241 25 06 2020 13 12 2020 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. 1662 Cell, Stem Cell and Cancer Topical formulation of tranilast improves hypertrophic scar in a rat model Darakhshan Sara Bagheri Fereshteh Kakabaraei Seyran Tahvilian Reza Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran Department of Anatomical Sciences & Cell Biology, Kermanshah University of Medical Sciences, Kermanshah, Iran Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran 1 9 2021 25 3 242 250 05 08 2020 13 12 2020 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. 1660 Gastrointestinal Physiology/Pharmacology Protective effects of date palm pollen extract on gentamicin-induced hepatotoxicity Mohamadi Yarijani Zeynab Madani Seyed Hamid Changizi-Ashtiyani Saeed Najafi Houshang Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Molecular Pathology Research Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran Department of Physiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 1 9 2021 25 3 251 260 02 08 2020 13 12 2020 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. 1637 Pharmacokinetics/Dynamics Antioxidant activity, phenolic and flavonoid content of Lawsonia inermis and Haplophyllum vermiculare Moulazadeh Alireza Kouhpayeh Seyyed Amin Ranjbar Razieh Dakhili Ardestani Amin Hekmat Maryam Azarnia Sara Najafipour Sohrab Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran Noncommunicable Disease Research Center, Fasa University of Medical Sciences, Fasa, Iran Medicinal Plant Research Center, Fasa University of Medical Sciences, Fasa, Iran 1 9 2021 25 3 261 269 17 06 2020 13 12 2020 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. 1676 Neurophysiology/Pharmacology The protective effects of apigenin on OLN-93 cellular model of cerebral stroke Miraee Samira Farhadi Mona Jameie Seyed Behnamedin Najafie Shabnam Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran 1 9 2021 25 3 270 278 09 09 2020 27 10 2020 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. 1599 Cell, Stem Cell and Cancer Nicotine effects on enzymatic antioxidant defenses in human breast and ovarian cell lines Yarahmadi Amir Mohammadi Neda Zal Fatemeh Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran 1 9 2021 25 3 279 287 01 04 2020 26 12 2020 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.