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Angiotensin 1-7 receptor blockade attenuates renal clearance and urine flow in reno-vascular hypertensive rats 2 102 103 2020/12/19 1399/9/29 2021/04/26 1400/2/6 Zahra Pezeshki Zahra Pezeshki Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Iran Mehdi Nematbakhsh Mehdi Nematbakhsh Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran Iran nematbakhsh@med.mui.ac.ir Mas receptor Two kidneys - one clip Hypertension Hilliard LM, Sampson AK, Brown RD, Denton KM. The "his and hers" of the renin-angiotensin system. Curr Hypertens Rep 2013; 15: 71-9.##Lee SH, Lee YH, Jung SW, Kim DJ, Park SH, Song SJ, et al. Sex-related differences in the intratubular renin-angiotensin system in two-kidney, one-clip hypertensive rats. Am J Physiol Renal Physiol 2019; 317: F670-82.##Patel SN, Ali Q, Samuel P, Steckelings UM, Hussain T. Angiotensin II type 2 receptor and receptor mas are colocalized and functionally interdependent in obese zucker rat kidney. Hypertension 2017; 70: 831-8.##Safari T, Nematbakhsh M, Hilliard LM, Evans RG, Denton KM. Sex differences in the renal vascular response to angiotensin II involves the Mas receptor. Acta Physiol (Oxf) 2012; 206: 150-6.##Sampson AK, Moritz KM, Denton KM. Postnatal ontogeny of angiotensin receptors and ACE2 in male and female rats. Gend Med 2012; 9: 21-32.##Sullivan JC, Gillis EE. Sex and gender differences in hypertensive kidney injury. Am J Physiol Renal Physiol 2017; 313: 1009-17.##Yim HE, Yoo KH. Renin-angiotensin system - considerations for hypertension and kidney. Electrolyte Blood Press 2008; 6: 42-50.## ##

Linear heart rate variability measures in sickle cell disease compared to the healthy control subjects: a systematic review and mete-analysis study 2 2 Introduction: Heart rate variability represents the performance of the cardiac autonomic nervous system (ANS) and is defined as the fluctuation of beat-to-beat between two successive R-waves (RR intervals). Accordingly, addressing the actions of the ANS in sickle cell disease helps in identifying the possible risk factors of sudden death. The clinical staging of the disease improves the diagnosis and the quality of the treatments. Methods: This systematic review analyzed the data of the basal autonomic reactions in sickle cell anemia (SCA) and sickle cell trait (SCT) patients compared to healthy people. In this study, 441 articles were retrieved from PubMed, ProQuest, SCOPUS, Embase, and Web of Science databases. Some of them were removed based on the inclusion and exclusion criteria, and finally, seven articles remained for analysis. Results: The data analysis of the included studies demonstrated that the vagal modulation at the basal condition decreased in SCA or SCT patients compared to the control group. Conclusion: The sympathovagal balance was altered in SCA or SCT patients, and an increasing trend was observed in sympathetic nerve activities. 104 118 2020/12/192020/07/8 1399/4/18 2021/04/262021/05/30 1400/3/9 Esmaeil Akbari Esmaeil Akbari Department of Physiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Iran Reza Alizadeh-Navaei Reza Alizadeh-Navaei Gastrointestinal Cancer Research Center, Mazandaran University of Medical Sciences, Sari, Iran Iran Motahareh Rouhi Ardeshiri Motahareh Rouhi Ardeshiri Department of Physiology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Iran m.roohi@mazums.ac.ir Heart rate variability Sickle cell anemia Sickle cell trait Autonomic nervous system Adebiyi AA, Oyebowale OM, Olaniyi AJ, Falase AO. Heart rate variability study in adult Nigerian subjects with sickle cell disease during vaso-occlusive crisis. Niger Postgrad Med J 2019; 26: 8.##Ai J, Epstein P, Gozal D, Yang B, Wurster R, Cheng Z. Morphology and topography of nucleus ambiguus projections to cardiac ganglia in rats and mice. Neuroscience 2007; 149: 845-60.##Assanasen C, Quinton RA, Buchanan GR. Acute myocardial infarction in sickle cell anemia. Pediatr Hematol Oncol J 2003; 25: 978-81.##Batra AS, Acherman RJ, Wong WY, Wood JC, Chan LS, Ramicone E, et al. Cardiac abnormalities in children with sickle cell anemia. Am J Hematol 2002; 70: 306-12.##Beitzke M, Pfister P, Fortin J, Skrabal F. Autonomic dysfunction and hemodynamics in vitamin B12 deficiency. Auton Neurosci 2002; 97: 45-54.##Bode- Thomas F, Hyacinth H, Ogunkunle O, Omotoso A. Myocardial ischaemia in sickle cell anaemia: evaluation using a new scoring system. Ann Trop Paediatr 2011; 31: 67-74.##Borenstein M, Hedges L, Rothstein H. Meta-analysis: Fixed effect vs. random effects. available at: Meta-analysis.com 2007.##Camm AJ, Malik M, Bigger JT, Breithardt G, Cerutti S, Cohen RJ, et al. Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Eur Heart J 1996; 17: 354-81.##Chalacheva P, Khaleel M, Sunwoo J, Shah P, Detterich JA, Kato RM, et al. Biophysical markers of the peripheral vasoconstriction response to pain in sickle cell disease. PloS One 2017; 12: e0178353.##Connes P, Barthelemy JC. Comment on 'Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia'. Physiol Meas 2008; 29: L1-2.##Connes P, Coates TD. Autonomic nervous system dysfunction: implication in sickle cell disease. C R Biol 2013; 336: 142-7.##de Andrade Martins W, Lopes HF, Consolim-Colombo FM, Gualandro SD, Arteaga-Fernández E, Mady C. Cardiovascular autonomic dysfunction in sickle cell anemia. Auton Neurosci 2012; 166: 54-9.##Deymann AJ, Goertz KK. Myocardial infarction and transient ventricular dysfunction in an adolescent with sickle cell disease. Pediatrics 2003; 111: 422.##Kardelen F, Tezcan G, Akcurin G, Ertug H, Yesilipek A. Heart rate variability in patients with thalassemia major. Pediatr Cardiol 2008; 29: 935-9.##Khaleel M, Puliyel M, Shah P, Sunwoo J, Kato RM, Chalacheva P, et al. Individuals with sickle cell disease have a significantly greater vasoconstriction response to thermal pain than controls and have significant vasoconstriction in response to anticipation of pain. Am J Hematol 2017; 92: 1137-45.##Kim J, Hakim F, Kheirandish-Gozal L, Gozal D. Inflammatory pathways in children with insufficient or disordered sleep. Respir Physiol Neurobiol 2011; 178: 465-74.##Lonergan GJ, Cline DB, Abbondanzo SL. Sickle cell anemia. Radiographics 2001; 21: 971-94.##Mestre JR, Hernandez A, Agramonte O, Hernandez P. Cardiovascular autonomic dysfunction in sickle cell anemia: a possible risk factor for sudden death? Clin Auton Res 1997; 7: 121-5.##Michelini LC, O'Leary DS, Raven PB, Nóbrega AC. Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex. Am J Physiol Heart Circ 2015; 309: H381-92.##Norris S, Johnson CS, Haywood LJ. Sickle cell anemia: does myocardial ischemia occur during crisis? J Natl Med Assoc 1991; 83: 209.##Perronne V, Roberts-Harewood M, Bachir D, Roudot-Thoraval F, Delord JM, Thuret I, et al. Patterns of mortality in sickle cell disease in adults in France and England. Hematol J 2002; 3: 56-60.##Peterson J, Welch V, Losos M, Tugwell PJ. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute 2011.##Quinn CT, Shull EP, Ahmad N, Rogers ZR, Buchanan GR. Prognostic significance of early vasoocclusive complications in children with sickle cell anemia. Blood 2005; 106: 3176.##Sangkatumvong S. Modeling of cardiovascular autonomic control in sickle cell disease. University of Southern California, 2011.##Sangkatumvong S, Coates TD, Khoo MC. Abnormal autonomic cardiac response to transient hypoxia in sickle cell anemia. Physiol Meas 2008a; 29: 655.##Sangkatumvong S, Coates TD, Wood JC, Meiselman HJ, Kato R, Detterich JA, et al. Time-varying analysis of autonomic control in response to spontaneous sighs in sickle cell anemia. In2010 Annual International Conference of the IEEE Engineering in Medicine and Biology 2010: 1626-9.##Sangkatumvong S, Khoo MC, Coates TD. Abnormal cardiac autonomic control in sickle cell disease following transient hypoxia. In2008 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 2008b Aug 20, pp. 1996-9.##Sangkatumvong S, Khoo MC, Kato R, Detterich JA, Bush A, Keens TG, et al. Peripheral vasoconstriction and abnormal parasympathetic response to sighs and transient hypoxia in sickle cell disease. Am J Respir Crit Care Med 2011; 184: 474-81.##Tsaras G, Owusu-Ansah A, Boateng F O, Amoateng-Adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am J Med 2009; 122: 507-12.##Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 2014; 14: 1-3.##Yokusoglu M, Nevruz O, Baysan O, Uzun M, Demirkol S, Avcu F, et al. The altered autonomic nervous system activity in iron deficiency anemia. Tohoku J Exp Med 2007; 212: 397-402.##Zygmunt A, Stanczyk J. Methods of evaluation of autonomic nervous system function. Arch Med Sci 2010; 6: 11-18.## ##

Therapeutic effects of Nigella sativa on asthma: a systematic review of clinical trial 2 2 Introduction: Nigella sativa (N. sativa)in the family of Ranunculaceae, has been traditionally used as food additive and spice. N. sativa showed protective effects on respiratory system including trachea responsiveness and lung inflammation in various animals’ models studies. The possible therapeutic effects of N. sativa on asthma were investigated in this systematic review study. Methods: The published studies were searched in the different databases including; PubMed, Web of Science (ISI), Scopus and Cochrane, until September 2020, by: (asthma) AND (“Nigella sativa”) OR (“Nigella sativa oil”) OR (Black seed). All unrelated articles such as duplicates, animal and review studies as well as clinical studies without control group were excluded from obtained studied. Then 9 articles were considered for further evaluation. Results: After analyzing 9 articles including 434 participants, these following results were achieved: N. sativa improved the asthma control test and pulmonary function tests values, while reduced respiratory symptoms including, cough and wheeze. Furthermore, N. sativa, reduced eosinophils count and serum levels of pro-inflammatory mediators such as interleukin-4 and immunoglobulin E, while increased production of anti-inflammatory mediator such as interferon-γ in the serum. Conclusion: The results of this systematic review article revealed that supplementation of N. sativa might be effective in the control or treatment of asthma.   119 126 2020/12/192020/07/82020/12/20 1399/9/30 2021/04/262021/05/302021/04/17 1400/1/28 Mohammad Reza Khazdair Mohammad Reza Khazdair Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran. Iran KhazdairMR@BUMS.ac.ir Alireza Amirabadizadeh Alireza Amirabadizadeh Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran. Iran Nigella sativa Asthma Airway inflammation Pulmonary function test Respiratory symptoms Ahmad J, Khan RA, Malik MA. A study of Nigella sativa oil in the management of wheeze associated lower respiratory tract illness in children. Afr J Pharm Pharmacol 2010; 4: 436-9.##Al-Jawad FH, Al-Razzuqi RA, Hashim HM, Ismael AH. Broncho-relaxant activity of Nigella sativa versus anthemisnobilis in chronic bronchial asthma; a comparative study of efficacy. IOSR J Pharmac 2012; 2: 81-3.##Al-Moamary MS, Alhaider SA, Al-Hajjaj MS, Al-Ghobain MO, Idrees MM, Zeitouni MO, et al. The Saudi initiative for asthma-2012 update: guidelines for the diagnosis and management of asthma in adults and children. Ann Thorac Med 2012; 7: 175.##Al Ameen N, Altubaigy F, Jahangir T, Mahday IA, Mohammed EA, Musa O. Effect of Nigella sativa and bee honey on pulmonary, hepatic and renal function in Sudanese in Khartoum state. J Med Plant Res 2011; 5: 6857-63.##Alavinezhad A, Khazdair MR, Boskabady MH. Possible therapeutic effect of carvacrol on asthmatic patients: A randomized, double blind, placebo‐controlled, Phase II clinical trial. Phytotherapy Research 2018; 32: 151-9.##Barlianto W, Rachmawati M, Irawan M, Wulandari D. Effects of Nigella sativa oil on Th1/Th2, cytokine balance, and improvement of asthma control in children. Paediatr Indones 2017; 57: 223-8.##Barlianto W, Wulandari D, Chusniyah M, Chandra Kusuma HMS, Prawiro SR. Improvement of th17/treg balance and asthma control test score by nigella sativa supplementation in asthmatic children: A new approach to managing asthma. Turk J Immunol 2018; 6: 1-7.##Barnes PJ. Drugs for asthma. British journal of pharmacology 2006; 147: S297-S303.##Bateman E, Hurd S, Barnes P, Bousquet J, Drazen J, FitzGerald M, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J 2008; 31: 143- 78.##Bordoni L, Fedeli D, Nasuti C, Maggi F, Papa F, Wabitsch M, et al. Antioxidant and antiinflammatory properties of Nigella sativa oil in human pre-adipocytes. Antioxidants 2019; 8: 51.##Boskabady M, Kiani S, Jandaghi P. Stimulatory effect of Nigella sativa on β2-adrenoceptors of guinea pig tracheal chains. Med j Islam Repub Iran 2004; 18: 153-158.##Boskabady M, Mohsenpoor N, Takaloo L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine 2010; 17: 707-13.##Boskabady MH, Farhadi J. The possible prophylactic effect of Nigella sativa seed aqueous extract on respiratory symptoms and pulmonary function tests on chemical war victims: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med 2008; 14: 1137-44.##Boskabady MH, Javan H, Sajady M, Rakhshandeh H. The possible prophylactic effect of Nigella sativa seed extract in asthmatic patients. Fundam Clin Pharmacol 2007; 21: 559-66.##Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma: from bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med 2000; 161: 1720-45.##Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB 2009; 11: 373-81.##Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 2004; 22: 789-815.##Durmuskahya C, Ozturk M. Ethnobotanical survey of medicinal plants used for the treatment of diabetes in Manisa, Turkey. Sains Malaysiana 2013; 42: 1431-8.##Düzelme D. Improvement of Th17/Treg balance and Asthma Control Test score by Nigella sativa supplementation in asthmatic children: a new approach to managing asthma. Turk J Immunol 2018; 6: 1-7.##Emeka LB, Emeka PM, Khan TM. Antimicrobial activity of Nigella sativa L. seed oil against multi-drug resistant Staphylococcus aureus isolated from diabetic wounds. Pak J Pharm Sci 2015; 28: 1985-90.##Gholamnezhad Z, Boskabady MH, Khazdair MR, Hosseini M, Abbasnejad M. Effect of fluticasone and salmeterol on tracheal responsiveness to ovalbumin and lung inflammation, administrated during and after sensitization. Sci World J 2014; 2014.##Gilani A, Aziz N, Khurram I, Chaudhary K, Iqbal A. Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses. J Pak Med Assoc 2001; 51: 115.##Greenberger P A. Therapy in the management of the rhinitis/asthma complex. Journal 2003; 24: 403-7.##Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res 2004; 18: 195-9.##Janssen L J, Killian K. Airway smooth muscle as a target of asthma therapy: history and new directions. Respir Res 2006; 7: 123.##Kalus U, Pruss A, Bystron J, Jurecka M, Smekalova A, Lichius JJ, et al. Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res 2003; 17: 1209-14.##Khazdair M, Boskabady M, Tabatabaee A, Hosseini M, Abbasnejad M. Effect of inhaled fluticasone and salmeterol on tracheal responsiveness and lung inflammation: influence of administration time and allergen-free period. Indian J Med Res 2013; 67: 78.##Khazdair MR. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol 2015; 2015.##Khazdair MR, Anaeigoudari A, Hashemzehi M, Mohebbati R. Neuroprotective potency of some spice herbs, a literature review. J Tradit Complement Med 2019a; 9: 98-105.##Khazdair MR, Anaeigoudari A, Kianmehr M. Anti-Asthmatic Effects of Portulaca Oleracea and its Constituents, a Review. J Pharmacopunct 2019b; 22: 122.##Koolen B, Pijnenburg M, Brackel H, Landstra A, Van den Berg N, Merkus P, et al. Comparing global initiative for asthma (GINA) criteria with the childhood asthma control test (C-ACT) and asthma control test (ACT). Eur Respir J 2011; 38: 561-6.##Koshak A, Wei L, Koshak E, Wali S, Alamoudi O, Demerdash A, et al. Nigella sativa supplementation improves asthma control and biomarkers: A randomized, double‐blind, placebo‐controlled trial. Phytother Res 2017; 31: 403-409.##Mahmood MS, Gilani A, Khwaja A, Rashid A, Ashfaq M. The in vitro effect of aqueous extract of Nigella sativa seeds on nitric oxide production. Phytother Res 2003; 17: 921-4.##Majdalawieh A F, Hmaidan R, Carr R I. Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity. J Ethnopharmacol 2010; 131: 268-75.##Mohebbati R, Shafei MN, Beheshti F, Soukhtanloo M, Roshan NM, Anaeigoudari A, et al. Mixed hydroalcoholic extracts of Nigella sativa and Curcuma longa improves adriamycininduced renal injury in rat. Saudi J Kidney Dis Transpl 2017; 28: 1270.##Mohebbatia R, Khazdair MR, Karimia S, Abbasnezhadd A. HepatoprotectiveEffects of Combination Hydroalcoholic Extracts of Nigella Sativa and Curcuma Longa on AdriamycinInduced Oxidative Stress in Rat. J Rep Pharm Sci 2017a; 6: 93-102.##Mohebbatia R, Khazdairb M R, Hedayatia M. Neuroprotective Effects of medicinal plants and their constituents on different induced neurotoxicity methods: A review. J Rep Pharm Sci 2017b; 6: 34-50.##Mokhtari-Zaer A, Norouzi F, Askari VR, Khazdair MR, Roshan NM, Boskabady M, et al. The protective effect of Nigella sativa extract on lung inflammation and oxidative stress induced by lipopolysaccharide in rats. J Ethnopharmacol 2020; 253: 112653.##Mortazavi Moghaddam SG, Kianmehr M, Khazdair MR. The possible therapeutic effects of some medicinal plants for chronic cough in children. 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Enriched environment restores passive avoidance memory impairment in a rat model of neuroinflammation 2 2 Introduction: Neuroinflammation is a primary pathophysiological condition that is associated with cognitive impairment and neurodegenerative diseases. The present study was designed to evaluate the effects of enriched environment (EE) on passive avoidance (PA) memory impairment caused by lipopolysaccharide (LPS) induced neuroinflammation. Methods: Twenty-eight male Wistar rats were assigned into the following groups: 1, control; 2, control+ EE; 3, LPS and 4, LPS+ EE. LPS injection (1mg/kg/i.p.) was done on days 1, 3, 5 and 7 of experiment. Two different housing conditions were used in this experiment, including a standard environment house and an enriched environment house. The passive avoidance task was used to examine animals learning and memory performance. The hippocampal level of interleukin-6 (IL-6) and brain-derived neurotrophic factor (BDNF) was also measured using sandwich-ELISA method. Results: Obtained data indicated that LPS significantly impaired passive avoidance memory, decreased the step-through latency and increased the time spent in the dark compartment of the LPS treated group compared to the control group. On the other hand, EE housing could significantly ameliorate memory impairment. Hippocampal IL-6 level was increased and BDNF was decreased in the LPS group, whereas EE could decrease and increase IL-6 and BDNF levels in the LPS+EE group, respectively. Conclusion: EE should probably be considered as an alternative strategy in neuroinflammatory diseases to minimize the memory impairment. 127 137 2020/12/192020/07/82020/12/202021/05/27 1400/3/6 2021/04/262021/05/302021/04/172021/08/7 1400/5/16 Arman Keymoradzadeh Arman Keymoradzadeh Student Research Committee, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Iran Mojtaba Hedayati Ch Mojtaba Hedayati Ch Department of Microbiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Iran Mahmood Abedinzade Mahmood Abedinzade Medical Biotechnology Research Center, School of Nursing, Midwifery and Paramedicine, Guilan University of Medical Sciences, Rasht, Iran Iran Behrooz Khakpour-Taleghani Behrooz Khakpour-Taleghani Neuroscience Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran Iran Khakpour@gums.ac.ir Inflammation Enriched environment Memory Passive avoidance Abdel-Mouttalib O. 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The effects of sildenafil on the hippocampal longterm potentiation in male rats 2 2 Introduction: The hippocampal nitric oxide/cGMP signaling pathway plays a crucial role in memory processing. Phosphodiesterase interacts with this signaling pathway. There are controversial reports regarding the effect of sildenafil, a phosphodiesterase inhibitor, on learning and memory. Therefore, the effects of acute administration (intrahippocampal/ intra-dentate gyrus injection) of sildenafil on long-term potentiation (LTP) of rats were investigated. Methods: The rats were anesthetized with urethane and placed in a stereotaxic device for field potential recording. After ensuring a steady-state baseline response, a single intraperitoneal injection of saline or sildenafil (2 and10 µg/kg) was done. The population spike amplitude, the excitatory postsynaptic potentials (EPSPs) slope and paired-pulse stimuli (as an inhibitory interneuron) were compared between groups. Results: The results showed that population spike amplitude and EPSP slope significantly increased after sildenafil administration (10µg/kg) following titanic stimulation compared with the saline group. However, the sildenafil (2µg/kg) and control groups showed no difference regarding population spike amplitude and EPSP slope. Sildenafil had no significant effects on recurrent inhibition. Conclusion: The obtained results indicated that acute administration of sildenafil improved LTP via direct effects on the hippocampus of intact rats. Thus, sildenafil may enhance learning and memory processing by modulating the hippocampal synapse. 138 144 2020/12/192020/07/82020/12/202021/05/272021/02/6 1399/11/18 2021/04/262021/05/302021/04/172021/08/72021/05/23 1400/3/2 Siamak Shahidi Siamak Shahidi Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran Mina Vishteh Mina Vishteh Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Iran Alireza komaki Alireza komaki Neurophysiology Research Center, 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 Sildenafil Phosphodiesterase inhibitor Long term potentiation Hippocampus Ahmadimoghaddam D, Zarei M, Mohammadi S, Izadidastenaei Z, Salehi I. 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Anti-inflammatory and antioxidative properties of date pollen in the gentamicin-induced renal toxicity 2 2 Introduction: Aminoglycoside antibiotics including gentamicin are used for treatment of gram-negative bacteria-induced infections; however, gentamicin has severe side effects such as nephrotoxicity. Date palm pollen (DPP), as a herbal medicine is believed to have some antiinflammatory and antioxidative stress effects. In this study the protective effect of DPP extract were evaluated after its phytochemical analysis on gentamicin-induced nephrotoxicity. Methods: Wistar rats allocated into five groups including control, sham, gentamicin and two groups that received gentamicin along with DPP extract (200 or 400 mg/kg). Plasma urea and creatinine concentrations were measured and oxidative stress was assessed by evaluating MDA, FRAP, CAT and SOD. NF-κB, TNF-α and ICAM-1 gene expression levels along with the leukocyte infiltration were measured for evaluating inflammation. Histopathological damages were also measured by studying H&E-stained tissue sections. Results: The gentamicin receiving group had increased plasma urea and creatinine, increased MDA, and decreased FRAP, CAT and SOD activities in the kidney. The gentamicin administration also increased the TNF-α, NF-κB and ICAM-1 gene expression, infiltration of leukocytes and tissue damages in the kidney. DPP extract caused a partial or complete recovery of all these damages. Conclusion: In conclusion, DPP extract protects the kidney against the side effects of gentamicin and improves its function and histopathological damages. The underlying mechanism is likely to decrease the NF-κB gene expression and consequently reducing pro-inflammatory cytokine genes expression, infiltration of leukocytes and oxidative stress. The DPP extract also increased the cellular antioxidant reserves. 145 157 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/24 1400/2/4 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/23 1400/3/2 Neda Omidian Neda Omidian Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Zeynab Mohamadi Yarijani Zeynab Mohamadi Yarijani Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Masoud Modarresi Masoud Modarresi Pharmacognosy and Biotechnology Department, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Aliashraf Godini Aliashraf Godini Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran Houshang Najafi Houshang Najafi Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran Iran hnajafi@kums.ac.ir Gentamicin Nephrotoxicity Date palm pollen Inflammation Oxidative stress Herbal medicine bbas FA, Abdel-Monem A. 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Am Fam Physician 2008; 78: 743-50.##Osborn DE, George NJR, Rao PN. Prostatodynia-physiological characteristics and rational management with muscle relaxants. Br J Urol 1981; 53: 621-3.##Randjelovic P, Veljkovic S, Stojiljkovic N, Sokolovic D, Ilic I. Gentamicin nephrotoxicity in animals: current knowledge and future perspectives. EXCLI J 2017; 16: 388-99.##Sahu BD, Kuncha M, Sindhura GJ, Sistla R. Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage. Phytomedicine 2013; 20: 453-60.##Sassen MC, Kim SW, Kwon TH, Knepper MA, Miller RT, Frokiaer J, et al. Dysregulation of renal sodium transporters in gentamicin-treated rats. Kidney Int 2006; 70: 1026-37.##Stojiljkovic N, Mihailovic D, Veljkovic S, Stoiljkovic M, Jovanovic I. Glomerular basement membrane alterations induced by gentamicin administration in rats. Exp Toxicol Pathol 2008; 60: 69-75.##Tahvilzadeh M, Hajimahmoodi M, Rahimi R. 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Protective effects of Cinnamomum zeylanicum and Zingiber officinale extract against CCl4-induced acute kidney injury in rats 2 2 Introduction: The toxicity induced by toxic substances and medications is one of the principal reasons for acute kidney injury. The purpose of this study was to investigate the effect of Cinnamomum zeylanicum and Zingiber officinale extracts on the kidney of the rats intoxicated with carbon tetrachloride (CCl4). Methods: In this study, thirty-six Wistar rats randomly divided into six groups: I) control, II) cinnamon 25mg/kg + ginger 125mg/kg, III) CCl4, IV) CCl4+ cinnamon 50mg/kg, V) CCl4+ ginger 250mg/kg, VI) CCl4+ cinnamon 25mg/kg and ginger 125mg/kg. Cinnamomum zeylanicum and Zingiber officinale extracts were injected for 14 days. On the 14th day, the rats in the CCl4 and the pretreatment groups were administered with 1mg/kg of CCl4 and olive oil mixture (1:1 v/v). Forty-eight hours after the injection of CCl4, blood samples were taken to conduct subsequent biochemical tests. Also, the kidney removed and histological alterations as well as oxidative markers were investigated. Results: The administration of CCl4 increased the levels of urea, uric acid, creatinine and malondialdehyde; while decreased the levels of serum albumin, total protein, total antioxidant capacity and renal tissue antioxidant enzymes. Pretreatment with Cinnamomum zeylanicum and Zingiber officinale extracts, especially with a combination of them, led to considerable improvement in these values compared to the CCl4 group. Conclusion: The results suggest that hydroalcoholic extracts of Cinnamomum zeylanicum and Zingiber officinale, alone or simultaneously, have protective effects against free radicals produced during CCl4 metabolism. 158 167 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/242021/01/20 1399/11/1 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/232021/05/11 1400/2/21 Lotfollah Rezagholizadeh Lotfollah Rezagholizadeh Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran Masoud Ojarudi Masoud Ojarudi Department of Biochemistry, Faculty of Sciences, Payame Noor University, Tehran, Iran Iran Alireza Moradi Alireza Moradi Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Iran Ramin Salimnejad Ramin Salimnejad Department of Anatomical Sciences and Pathology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran salimnegad67@gmail.com Abbas Khonakdar-Tarsi Abbas Khonakdar-Tarsi Department of Biochemistry and Genetics, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran Iran Somaieh Matin Somaieh Matin Department of Internal Medicine, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran Iraj Feizi Iraj Feizi Department of Surgery, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran Alireza Mohammadnia Alireza Mohammadnia Department of Health information technology management, School of medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran Mohammad Mazani Mohammad Mazani Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran Iran Cinnamomum zeylanicum Zingiber officinale Antioxidant Carbon tetrachloride Acute kidney injury. Abd-Allah GA, El-Bakry KA, Bahnasawy MH, El-Khodary ES. Protective effects of curcumin and ginger on liver cirrhosis induced by carbon tetrachloride in rats. Int J Pharmacol 2016; 12: 361-9.##Adewole S, Salako A, Doherty O, Naicker T. Effect of melatonin on carbon tetrachlorideinduced kidney injury in Wistar rats. Afr J Biomed Res 2007; 10.##Aebi H. Catalase in vitro. Meth Enzymol 1984; 105: 121-6.##Alibakhshi T, Khodayar MJ, Khorsandi L, Rashno M, Zeidooni L. Protective effects of zingerone on oxidative stress and inflammation in cisplatin-induced rat nephrotoxicity. Biomed Pharmacother 2018; 105: 225-32.##Bartosz G. Total antioxidant capacity. Adv Clin Chem 2003; 219-92.##Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem 1996; 239: 70-6.##Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-54.##Cachofeiro V, Goicochea M, De Vinuesa SG, Oubiña P, Lahera V, Luño J. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease: New strategies to prevent cardiovascular risk in chronic kidney disease. Kidney Int 2008; 74: 4-S9.##Chávez-Morales RM, Jaramillo-Juárez F, Rodríguez-Vázquez ML, Martínez-Saldaña MC, Del Río FP, Garfias-López JA. The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a single and low dose of carbon tetrachloride in adult male rats. Exp Toxicol Pathol 2017; 69: 430-4.##Chericoni S, Prieto JM, Iacopini P, Cioni P, Morelli I. In vitro activity of the essential oil of Cinnamomum zeylanicum and eugenol in peroxynitrite-induced oxidative processes. J Agric Food Chem 2005; 53: 4762-5.##Cifci A, Tayman C, Yakut HI, Halil H, Cakir E, Cakir U, et al. Ginger (Zingiber officinale) prevents severe damage to the lungs due to hyperoxia and inflammation. Turk J Med Sci 2018; 48: 892-900.##Eidi A, Mortazavi P, Bazargan M, Zaringhalam J. Hepatoprotective activity of cinnamon ethanolic extract against CCI4-induced liver injury in rats. Excli J 2012; 11: 495.##Ganie SA, Haq E, Masood A, Zargar MA. Amelioration of carbon tetrachloride induced oxidative stress in kidney and lung tissues by ethanolic rhizome extract of Podophyllum hexandrum in Wistar rats. J Med Plant Res 2010; 4: 1673-7.##Hismiogullari AA, Hismiogullari SE, Karaca O, Sunay FB, Paksoy S, Can M, et al. The protective effect of curcumin administration on carbon tetrachloride (CCl 4)-induced nephrotoxicity in rats. Pharmacol Rep 2015; 67: 410-6.##Kang DH, Nakagawa T, Feng L, Watanabe S, Han L, Mazzali M, et al. A role for uric acid in the progression of renal disease. J Am Soc Nephrol 2002; 13: 2888-97.##Kumar S, Kumar R, Dwivedi A, Pandey AK. In vitro antioxidant, antibacterial, and cytotoxic activity and in vivo effect of Syngonium podophyllum and Eichhornia crassipes leaf extracts on isoniazid induced oxidative stress and hepatic markers. BioMed Res Int 2014; 2014.##Lin L, Cui F, Zhang J, Gao X, Zhou M, Xu N, et al. Antioxidative and renoprotective effects of residue polysaccharides from Flammulina velutipes. Carbohydr Polym 2016; 146: 388-95.##Maghsoudi S, Gol A, Dabiri S, Javadi A. Preventive effect of ginger (Zingiber officinale) pretreatment on renal ischemia-reperfusion in rats. Eur Surg Res 2011; 46: 45-51.##Mahmoud MF, Diaai AA, Ahmed F. Evaluation of the efficacy of ginger, Arabic gum, and Boswellia in acute and chronic renal failure. Ren Fail 2012; 34: 73-82.##Mazani M, Mahmoodzadeh Y, Asl MM, Banaei S, Rezagholizadeh L, Mohammadnia A. Renoprotective effects of the methanolic extract of Tanacetum parthenium against carbon tetrachloride-induced renal injury in rats. Avicenna J Phytomed 2018; 8: 370.##Mazani M, Ojarudi M, Banaei S, Salimnejad R, Latifi M, Azizi H, et al. The protective effect of cinnamon and ginger hydro‐alcoholic extract on carbon tetrachloride‐induced testicular damage in rats. Andrologia 2020; 52: 13651.##Ogeturk M, Kus I, Colakoglu N, Zararsiz I, Ilhan N, Sarsilmaz M. Caffeic acid phenethyl ester protects kidneys against carbon tetrachloride toxicity in rats. J Ethnopharmacol 2005; 97: 273- 80.##Preethi KC, Kuttan R. Hepato and reno protective action of Calendula officinalis L. Flower Extract. 2009.##Radulović NS, Randjelović PJ, Stojanović NM, Ilić IR, Miltojević AB, Stojković MB, et al. Effect of two esters of N-methylanthranilic acid from Rutaceae species on impaired kidney morphology and function in rats caused by CCl4. Life Sci 2015; 135: 110-7.##Rajesh MG, Latha MS. Protective activity of Glycyrrhiza glabra Linn. on carbon tetrachlorideinduced peroxidative damage. Indian J Pharmacol 2004; 36: 284.##Shahbazi F, Dashti-Khavidaki S, Khalili H, Lessan-Pezeshki M. Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature. J Pharm Pharm Sci 2012; 15: 112- 23.##Sharafeldin K, Rizvi MR. Effect of traditional plant medicines (Cinnamomum zeylanicum and Syzygium cumini) on oxidative stress and insulin resistance in streptozotocin-induced diabetic rats. J Basic & Appl Zool 2015; 72: 126-34.##Sharma UK, Kumar R, Gupta A, Ganguly R, Pandey AK. Renoprotective effect of cinnamaldehyde in food color induced toxicity. 3 Biotech 2018; 8: 1-5.##Shirpoor A, Rezaei F, Fard AA, Afshari AT, Gharalari FH, Rasmi Y. Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration. Biomed Pharmacother 2016; 84: 698-704.##Shokoohi M, Soltani M, Abtahi-Eivary SH, Niazi V, Poor MJ, Ravaei H, et al. Effect of hydro-- alcoholic extract of Olea europaea on apoptosis--related genes and oxidative stress in a rat model of torsion/detorsion--induced ovarian damage. Asian Pac J Reprod 2019; 8: 148.##Subasini U, Thenmozhi S, Rajamanickam GV, Dwivedi GD. Reno-protective and Membrane Stabilizing Effect of Dioscorea bulbifera L. in CCL4 Induced Toxicity in Rats. Am J Life Sci Res 2015; 3.##Sudjarwo SA, Giftania Wardani Sudjarwo K. Protective effect of curcumin on lead acetateinduced testicular toxicity in Wistar rats. Res Pharm Sci 2017; 12: 381.##Tiong HY, Huang P, Xiong S, Li Y, Vathsala A, Zink D. Drug-induced nephrotoxicity: clinical impact and preclinical in vitro models. Mol pharm 2014; 11: 1933-48.##Trujillo J, Chirino YI, Molina-Jijón E, Andérica-Romero AC, Tapia E, Pedraza-Chaverrí J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol 2013; 1: 448-56.##Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978; 86: 271-8.##Yanishlieva NV, Marinova E, Pokorný J. Natural antioxidants from herbs and spices. Eur J Lipid Sci Technol 2006; 108: 776-93.##Yilmaz-Ozden T, Can A, Karatug A, Pala-Kara Z, Okyar A, Bolkent S. Carbon tetrachlorideinduced kidney damage and protective effect of Amaranthus lividus L. in rats. Toxicol Ind Health 2016; 32: 1143-52.##Yılmaz N, Seven B, Timur H, Yorgancı A, İnal HA, Kalem MN, et al. Ginger (zingiber officinale) might improve female fertility: A rat model. J Chin Med Assoc 2018; 81: 905-11.##Yoshioka H, Usuda H, Nonogaki T, Onosaka S. Carbon tetrachloride-induced lethality in mouse is prevented by multiple pretreatment with zinc sulfate. J Toxicol Sci 2016; 41: 55-63.##Yousefi H, Ahmadiasl N, Salimnejad R, Bagheri E, Roshangar L, Alihemmati A. Effects of renal ischemia-reperfusion on biochemical factors and histopathological alterations in the liver of male rats. Physiol Pharmacol 2019; 23: 44-50.## ##

Time course of renal ischemia/reperfusion and distance organ: lung dysfunction in male and female rats 2 2 Introduction: Renal ischemia/reperfusion injury (IRI) may influence distance organ such as lung. The severity of IRI induced- lung insult can be affected by gender and reperfusion time alteration. The aim of this study was to determine gender differences in renal IR inducedlung injury in different reperfusion time. Methods: Eighty male and female rats were assigned into 8 groups, 4 groups in each gender including: sham, renal ischemia for 45min by clamping renal vessels followed by 3, 24 or 48h reperfusion. Blood samples were obtained for measuring the serum level of blood urea nitrogen (BUN), creatinine (Cr), nitrite and malondialdehyde (MDA). The kidneys and lung tissues were removed and used for MDA and nitrite measurements and the histological changes evaluation. The lung water content was calculated. Results: In both genders, the rise in Cr and BUN reached the peak at 24h reperfusion. A significant increment was seen in female serum level of nitrite compared with males after 3h reperfusion. The renal MDA level of male increased during 3h reperfusion but not seen in females. The enhanced lung and renal tissues damages were depended to reperfusion time in both genders. The water content of lung was reduced in 3h of reperfusion groups. Conclusion: Sex effects and the time of reperfusion may be the important factors to consider clinical therapeutic of renal IRI as well as its impact on remote organs. 168 177 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/242021/01/202020/11/19 1399/8/29 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/232021/05/112021/06/14 1400/3/24 Fariba Azarkish Fariba Azarkish Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Iran Ali Atash Ab Parvar Ali Atash Ab Parvar Department of Pathology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Iran Mehdi Nematbakhsh Mehdi Nematbakhsh Water and Electrolytes Research Center/Department of Physiology, Isfahan University of Medical Sciences, Isfahan, Iran Iran Aghdas Dehghani Aghdas Dehghani Endocrinology and Metabolism Research Center/Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Iran Aghdas.dehghani@hums.ac.ir Renal ischemia-reperfusion Lung Gender Distant organ Abogresha NM, Greish SM, Abdelaziz EZ, Khalil WF. Remote effect of kidney ischemiareperfusion injury on pancreas: role of oxidative stress and mitochondrial apoptosis. Arch Med Sci 2016; 12: 252.##Azarkish F, Nematbakhsh M, Fazilati M, Talebi A, Pilehvarian AA, Pezeshki Z, et al. Nacetylcysteine prevents kidney and lung disturbances in renal ischemia/reperfusion injury in rat. Int J Prev Med 2013; 4: 1139-46.##Barp J, Araújo ASdR, Fernandes TRG, Rigatto KV, Llesuy S, Belló-Klein A, et al. Myocardial antioxidant and oxidative stress changes due to sex hormones. Braz J Med Biol Res 2002; 35: 1075-81.##Basu RK, Wheeler, DS. Effects of ischemic acute kidney injury on lung water balance: nephrogenic pulmonary edema? Pulm Med 2011; 2011.##Basu RK, Wheeler DS. Kidney-lung cross-talk and acute kidney injury. Pediatr Nephrol 2013; 28: 2239-48.##Campanholle G, Landgraf RG, Gonçalves GM, Paiva VN, Martins JDO, Wang PHM, Teixeira VPA. Lung inflammation is induced by renal ischemia and reperfusion injury as part of the systemic inflammatory syndrome. Inflamm Res 2010; 59: 861-9.##Choi EK, Jung H, Kwak KH, Yi SJ, Lim JA, Park SH, et al. Inhibition of oxidative stress in renal ischemia-reperfusion injury. Anesth Analg 2017; 124: 204-13.##Dehghani A, Saberi S, Nematbakhsh M. Role of Mas receptor antagonist A799 in renal blood flow response to Ang 1-7 after bradykinin administration in ovariectomized estradiol-treated rats. Adv Pharmacol Pharm Sci 2015; 2015.##Doi K, Ishizu T, Fujita T, Noiri E. Lung injury following acute kidney injury: kidney-lung crosstalk. Clin Exp Nephrol 2011; 15: 464-70.##Granger DN, Kvietys PR. Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox biology 2015; 6: 524-51.##Hassoun HT, Lie ML, Grigoryev DN, Liu M, Tuder RM, Rabb H. Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis. Am J Physiol Renal Physiol 2009; 297: 125-37.##Ibrahim IY, Elbassuoni EA, Ragy MM, Habeeb WN. Gender difference in the development of cardiac lesions following acute ischemic-reperfusion renal injury in albino rats. Gen Physiol Biophys 2013; 32: 421-8.##Kao CC, Yang WS, Fang JT, Liu KD, Wu VC. Remote organ failure in acute kidney injury. J Formos Med Assoc 2019; 118: 859-66.##Kei S. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978; 90: 37-43.##Kher A, Meldrum KK, Wang M, Tsai BM, Pitcher JM, Meldrum DR. Cellular and molecular mechanisms of sex differences in renal ischemia-reperfusion injury. Cardiovasc Res 2005; 67: 594-603.##Kiris I, Kapan S, Kılbas A, Yılmaz N, Altuntaş I, Karahan N, et al. The protective effect of erythropoietin on renal injury induced by abdominal aortic-ischemia-reperfusion in rats. J Surg Res 2008; 149: 206-13.##Klein CL, Hoke TS, Fang WF, Altmann CJ, Douglas IS, Faubel, S. Interleukin-6 mediates lung injury following ischemic acute kidney injury or bilateral nephrectomy. Kidney Int 2008; 74: 901-9.##Ko SF, Yip HK, Zhen YY, Lee CC, Lee CC, Huang SJ, et al. Severe bilateral ischemicreperfusion renal injury: hyperacute and acute changes in apparent diffusion coefficient, T1, and T2 mapping with immunohistochemical correlations. Sci Rep 2017; 7: 1-10.##Kramer AA, Postler G, Salhab KF, Mendez C, Carey LC, Rabb H. Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Kidney Int 1999; 55: 2362-7.##Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA, et al. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest 2003; 112: 915-923.##Lü P, Liu F, Wang CY, Chen DD, Yao Z, Tian Y,. Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide. World J Gastroenterol 2005; 11: 3441.##Moeini M, Nematbakhsh M, Fazilati M, Talebi A, Pilehvarian AA, Azarkish F, et al. Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model. Int J Prev Med 2013; 4: 648-55.##Müller V, Losonczy G, Heemann U, Vannay Á, Fekete A, Reusz G, et al. Sexual dimorphism in renal ischemia-reperfusion injury in rats: possible role of endothelin. Kidney Int 2002; 62: 1364- 71.##Neugarten J, Golestaneh L, Kolhe NV. Sex differences in acute kidney injury requiring dialysis. BMC Nephrol 2018; 19: 131.##aladino JD, Hotchkiss JR, Rabb H. Acute kidney injury and lung dysfunction: a paradigm for remote organ effects of kidney disease? Microvasc Res 2009; 77: 8-12.##Park KM, Kim JI, Ahn Y, Bonventre AJ, Bonventre JV. Testosterone is responsible for enhanced susceptibility of males to ischemic renal injury. J Biol Chem 2004; 279: 52282-92.##Reckelhoff JF, Hennington BS, Moore AG, Blanchard EJ, Cameron J. Gender differences in the renal nitric oxide (NO) system. Am J Hypertens 1998; 11: 97-104.##Saberi S, Dehghani A, Nematbakhsh M. Role of Mas receptor in renal blood flow response to angiotensin-(1-7) in ovariectomized estradiol treated rats. Res Pharm Sci 2016; 11: 65-72.##Schofield ZV, Woodruff TM, Halai R, Wu M CL, Cooper MA. Neutrophils-a key component of ischemia-reperfusion injury. Shock 2013; 40: 463-70.##Sener G, Sehirli AÖ, Keyer‐Uysal M, Arbak S, Ersoy Y, Yeğen BÇ. The protective effect of melatonin on renal ischemia-reperfusion injury in the rat. J Pineal Res 2002; 32: 120-6.##Tanaka R, Yazawa M, Morikawa Y, Tsutsui H, Ohkita M, Yukimura T, et al. Sex differences in ischaemia/reperfusion-induced acute kidney injury depends on the degradation of noradrenaline by monoamine oxidase. Clin Exp Pharmacol Physiol 2017; 44: 371-7.##Tanaka R, Tsutsui H, Ohkita M, Takaoka M, Yukimura T, Matsumura, Y. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system. Eur J Pharmacol 2013; 714: 397-404.##Tripatara P, Patel NSA, Webb A, Rathod K, Lecomte F MJ, Mazzon E, et al. Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. J Am Soc Nephrol 2007; 18: 570-80.##Wei Q, Dong Z. Mouse model of ischemic acute kidney injury: technical notes and tricks. Am J Physiol Renal Physiol 2012; 303: 1487-94.##Yang Shun, Chou Wei-Ping, Pei Ling. Effects of propofol on renal ischemia/reperfusion injury in rats. Exp Ther Med 2013; 6: 1177-83.## ##

RGS4 inhibition and the effects of adrenoceptor and cholinoceptor agonists on isolated left atrium and aorta of normal and diabetic rats 2 2 Introduction: “Regulator of G protein signaling” (RGS) proteins are a family of various proteins that are expressed in different tissues and accelerate hydrolysis rate of GTP to GDP by several thousand-fold increase in GTPase activity of Gα subunit. Thus, they act as negative regulators of G protein-coupled receptors (GPCRs) signaling. In this study, the effect of CCG-50014, a RGS4 inhibitor, on isolated aorta and left atrium of normal and diabetic rats has been investigated. Methods: Isolated aorta was treated with increasing concentrations of phenylephrine and acetylcholine. Isolated left atrium was treated with increasing concentrations of acetylcholine and isoprenaline; both in the absence and presence of CCG-50014. The pEC50 (negative logarithm of the concentration which produces half maximal response) and maximum response of each compound were extracted from concentration-response curves. Results: Pre-treatment of aorta with CCG-50014 had no important effect on the response to phenylephrine and acetylcholine. CCG-50014 decreased isoprenaline inotropic potency on normal atrium but had no effect on its maximum response. In diabetic atrium, CCG-50014 dramatically reduced both the pEC50 and maximum response of isoprenaline. CCG-50014 did not affect normal atrium response to acetylcholine but in diabetic atrium, it caused a small yet significant decrease in the pEC50 of acetylcholine while increased its maximum relaxing effect. Conclusion: It seems that RGS4 is not involved in the termination of GPCRs signaling in rat aorta. In atrium, RGS4 inhibition unexpectedly results in attenuation of β-adrenoceptormediated atrial contractility, which is much more prominent in diabetes. 178 187 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/242021/01/202020/11/192020/10/10 1399/7/19 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/232021/05/112021/06/142021/04/26 1400/2/6 Mohsen Goharinia Mohsen Goharinia Department of Pharmacology, Fasa University of Medical Sciences, Fasa, Iran Iran Hossein Mirkhani Hossein Mirkhani Department of Pharmacology, Shiraz University of Medical Sciences, Shiraz, Iran Iran mirkhanh@sums.ac.ir Regulator of G-protein signaling (RGS) proteins Atrium Aorta Diabetes Isoprenaline Ajay M, Achike FI, Mustafa AM, Mustafa MR. Effect of quercetin on altered vascular reactivity in aortas isolated from streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 2006; 73: 1-7.##Altan VM, Arioglu E, Guner S, Ozcelikay AT. The influence of diabetes on cardiac betaadrenoceptor subtypes. Heart Fail Rev 2007; 12: 58-65.##Blazer LL, Zhang H, Casey EM, Husbands SM, Neubig RR. A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochem 2011; 50: 3181-92.##Carrier GO, Edwards AD, Aronstam RS. Cholinergic supersensitivity and decreased number of muscarinic receptors in atria from short-term diabetic rats. J Mol Cell Cardiol 1984; 16: 963-5.##Chen IS, Furutani K, Inanobe A, Kurachi Y. RGS4 regulates partial agonism of the M2 muscarinic receptor-activated K+ currents. J Physiol 2014; 592: 1237-48.##Cho H, Harrison K, Schwartz O, Kehrl JH. The aorta and heart differentially express RGS (regulators of G-protein signalling) proteins that selectively regulate sphingosine 1- phosphate, angiotensin II and endothelin-1 signalling. Biochem J 2003; 371: 973-80.##Dall'ago P, Schaan BD, da Silva VO, Werner J, da Silva Soares PP, de Angelis K, et al. Parasympathetic dysfunction is associated with baroreflex and chemoreflex impairment in streptozotocin-induced diabetes in rats. Auton Neurosci 2007; 131: 28-35.##Gu S, Cifelli C, Wang S, Heximer SP. RGS proteins: identifying new GAPs in the understanding of blood pressure regulation and cardiovascular function. Clin Sci 2009; 116: 391-9.##Hao J, Michalek C, Zhang W, Zhu M, Xu X, Mende U. Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation. J Mol Cell Cardiol 2006; 41: 51-61.##Hendriks-Balk MC, Peters SL, Michel MC, Alewijnse AE. Regulation of G protein-coupled receptor signalling: focus on the cardiovascular system and regulator of G protein signalling proteins. Eur J Pharmacol 2008; 585: 278-91.##Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. 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Therapeutic effects of exercise, escitalopram and exercise-accompanied escitalopram on brain functions in rats with depression 2 2 Introduction: Depression impairs brain functions and memory processes. In a state of depression, escitalopram (as an antidepressant drug) and exercise (as an alternative lifestyle) both affect brain functions. Therefore, this study compared the therapeutic effects of exercise, using escitalopram at two different doses and exercise-accompanied escitalopram on different aspects of brain functions in rats with depression. Methods: Male rats were randomly allocated into nine different groups of control, sham, depression, depression-rest, depression-exercise, depression-escitalopram 10, depressionescitalopram 20, depression-escitalopram 10-exercise and depression-escitalopram 20-exercise. Chronic restraint stress (6h/day, 14 days) was applied to induce depression. The escitalopram injections and treadmill running (1h/day, 14 days) were performed after the stress-induced depression. Moreover, different aspects of brain functions like learning, memory, memory consolidation and locomotor activity were evaluated via the passive avoidance test. Results: The results indicated that depression disrupted learning, memory and memory consolidation. Escitalopram at a dose of 20mg/kg, exercise-accompanied escitalopram 20mg/ kg and only exercise improved them significantly. In rats with depression, escitalopram at a dose of 10mg/kg (with and without exercise) enhanced memory in depression non-significantly. Moreover, the locomotor activity was decreased in groups with exercise-accompanied escitalopram 20mg/kg and exercise compared to only allowing a rest period after depression. Conclusion: Overall, escitalopram 20mg/kg, exercise-accompanied escitalopram 20mg/kg and only exercise had therapeutic effects on memory improvement in subjects with depression. Since the combination of escitalopram 20mg/kg and exercise had a partial additive effect, it was the best treatment protocol for reversing the memory deficits in rats with depression. 188 199 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/242021/01/202020/11/192020/10/102021/02/13 1399/11/25 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/232021/05/112021/06/142021/04/262021/05/17 1400/2/27 Mahshid Zamani Mahshid Zamani Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran Maryam Radahmadi Maryam Radahmadi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran m_radahmadi@med.mui.ac.ir Parham Reisi Parham Reisi Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Iran Escitalopram Exercise Depression Chronic stress Memory Locomotor activity Arida RM, Scorza CA, da Silva AV, Scorza FA, Cavalheiro EA. 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Acetylsalicylic acid enhanced neurotrophic profile of epidermal neural crest stem cells: a possible approach for the combination therapy 2 2 Introduction: Stem cell therapy is considered as a promising strategy to treat neurological disorders. Amongst different cell types that are recruited under these devastating conditions, epidermal neural crest stem cells (EPI-NCSCs) are known as potential candidates. Acetylsalicylic acid (ASA or aspirin) is one of the commonly prescribed drugs that might affect the therapeutic potential of the transplanted stem cells. Hence, the present study aimed to evaluate the effects of ASA on the expression of fundamental growth factors involved in restorative pathways expressed by EPI-NCSCs in vitro for possible combination therapy’s purpose. Methods: EPI-NCSCs were obtained from the rat’s hair follicle. The appropriate ASA concentration to treat the cells was defined based on the MTT assay and then the obtained cells were treated with 80 or 800µM ASA for 1, 3 or 7 days. The relative expressions of Bdnf, Gdnf, Ngf, Neurotrophin-3, Vegf, Gfap, and doublecortin were finally assessed by qRT-PCR. Results: The obtained data revealed that the growth factors expressions are influenced by concentration and duration of the treatment applied. One-day ASA treatment was found to be able to increase the expression of all the evaluated genes, except Gdnf and doublecortin, which elevated three days later. Herein, seven-day treatment of stem cells with 800µM ASA resulted in higher levels of Bdnf, Vegf, and doublecortin. Conclusion: Therefore, combination of aspirin and EPI-NCSCs might increase the therapeutic potential of these stem cells to treat neurological disorders. 200 212 2020/12/192020/07/82020/12/202021/05/272021/02/62021/04/242021/01/202020/11/192020/10/102021/02/132021/02/14 1399/11/26 2021/04/262021/05/302021/04/172021/08/72021/05/232021/05/232021/05/112021/06/142021/04/262021/05/172021/03/9 1399/12/19 Seyedeh Shaghayegh Zafarmand Seyedeh Shaghayegh Zafarmand Zarghan Branch, Islamic Azad University, Zarghan, Iran Iran Mohammad Saied Salehi Mohammad Saied Salehi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Mohammad Javad Mokhtari Mohammad Javad Mokhtari Young Research and Elite Club, Zarghan Branch, Islamic Azad University, Zarghan, Iran Iran Anahid Safari Anahid Safari Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Sareh Pandamooz Sareh Pandamooz Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Mehdi Dianatpour Mehdi Dianatpour Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran Afshin Borhani-Haghighi Afshin Borhani-Haghighi Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Iran neuro.ab@gmail.com Aspirin ASA EPI-NCSCs Growth factors Neurological disorders Abd Rahman F, Mohd Ali J, Abdullah M, Abu Kasim NH, Musa S. 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