Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Proton pump inhibitors in Iranian population: from clinical regimens to pharmacogenomics 230 249 EN Kowsar Bagherzadeh Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran Sepideh Safari Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran Massoud Amanlou Department of Medicinal Chemistry, Faculty of Pharmacy and Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran Manijeh Motevalian Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran Proton pump inhibitors (PPIs) are one of the highly prescribed or over-the-counter available medications among Iranians, mainly to treat conditions such as helicobacter pylori infection, gastroesophageal reflux disease or frequent heartburn. In recent years, several reports have shown potential adverse effects of PPI administration among which cardiovascular adverse events, myocardial infarction and chronic kidney disease are considered as the greatest risks. Recent addition of proton pump inhibitors to the list of medications on Beers Criteria of Potentially Inappropriate Drugs has arisen significant concerns about their safety. This review aims at providing an up-to date overview of PPIs indications and their pharmacogenomics and pharmacokinetics in Iranian population. The focus of this review is on PPIs regimens in Iranian population and then it is compared with the reported studies performed on other ethnic groups around the world. An extensive review of the literature was carried out and data under various sections were identified using a computerized literature search via Pubmed, Web of Science, Google Scholar and some local search engines. All abstracts and full text articles were examined and most relevant papers were selected for inclusion in this review. Also several expert internalists were interviewed for their clinical experiences in this field.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Treadmill exercise improves memory and increases hippocampal BDNF in a rat model of Alzheimer's Disease 250 256 EN Rokhsareh Abshenas Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran Tayebe Artimani Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran Iraj Amiri Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran Siamak Shahidi Physiology Department, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Sara Soleimani Asl Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran Introduction: Alzheimer’s disease is strongly correlated with learning and memory impairments. As exercise can enhance memory and learning, in this study, we have investigated the effects of treadmill exercise on memory impairment in amyloid β (Aβ)- treated rats focusing on brain-derived neurotrophic factor (BDNF) expression. Methods: Wistar male rats received intracerebroventricular (ICV) injection of Aβ and exercised on a treadmill for one month. Memory function was assessed using Morris water maze (MWM) and avoidance learning tasks. The level of BDNF was examined by the ELISA test. Results: The results of MWM and avoidance learning tasks showed that treadmill exercise could improve Aβ- induced memory impairment significantly. Moreover, BDNF expression increased following exercise in the Aβ- treated rats. Conclusion: The present results suggested that treadmill exercise may improve memory in Alzheimer’s disease by increasing BDNF level in the hippocampus.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Protective effect of CoQ10 and Artemisia sieberi combination on PC12 cells model of 6-hydroxydopamine induced toxicity 257 267 EN Seyed Behnamedin Jameie Neuroscience Research Center, Iran University of Medical Sciences, Tehran, Iran Mona Farhadi Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Kamelia Gharibzad Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran Introduction: Parkinson's disease (PD) is a progressive neurodegenerative disease that affects motor function. The etiology of PD is unknown and routine therapies temporarily relieve the symptoms. Neuroprotective based therapies preserve the remaining neurons and prevent the progression of PD. Artemisia sieberi has anti-cancer and neuroprotective effects. The CoQ10 also is an antioxidant that has proven anti-inflammatory and antioxidant properties. In order to study the effect of Artemisia and CoQ10 on the PD cellular model, the present research was designed. Methods: PC12 cells were treated with different concentrations of 6-hydroxydopamine. Then the cells divided into the control (cells were not treated), DMSO group and experimental groups treated with the different concentrations of Artemisia sieberi extracts, CoQ10 and combination of them for 24h. The viability of the cells, reactive oxygen species (ROS) generation and p53 expression were evaluated. Results: Artemisia at a concentration of 200μg/ml and CoQ10 at a concentration of 75μg/ml significantly increased cell viability in the treated groups after 24h. Their combination showed better and more significant results compared to each alone. Hoechst staining showed significantly reduced apoptosis in treated cells. ROS generation reduced in the treated groups with better results for the combination-treated groups. The same results acquired for the expression of P53 in the treated cells. Conclusion: Regarding the results of both Artemisia and CoQ10, it could be concluded that they act synergistically with possible similar pathways. Although the Artemisia itself showed significant results, it seems that the combination method might have more therapeutic effects.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Long-term administration of intranasal insulin improves peripheral glucose concentration in diabetic male rats 268 275 EN Nihad Torabi Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maryam Nazari Department of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Tehran, Iran Javad Fahanik-Babaei Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Afsaneh Eliassi Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Introduction: Experiments in rodents and humans suggest that short-term intranasal insulin administration, which is known to reach the brain, does not affect peripheral glucose concentration under diabetic conditions. Methods: In this work, we provide evidence for the effect of intranasal insulin (10 IU/rat/day for 3 or 10 days) on serum insulin and glucose in streptozotocin-diabetic male rats using insulin measurements in the brain and periphery and a serum glucose assay 18 hours after three or ten days of nasal insulin administration. Results: Our findings revealed peripheral insulin increased and glucose level decreased in the diabetic male rats. Based on insulin kinetics, it seems that brain insulin directly or indirectly regulates serum insulin and glucose metabolism under diabetic conditions. Conclusion: Our results may suggest an insight into the therapeutic benefits of nasal insulin in diabetes.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Protective effect of zinc sulfate and continuous/interval training on liver oxidative stress in morphine-withdrawal syndrome in rats 276 284 EN Sahar Hasani Student Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Hassan Ghasemi Department of Clinical Biochemistry, Abadan School of Medical Sciences, Abadan, Iran Akram Ranjbar Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Reza Ghahremani Department of Exercise Physiology, Faculty of Sport Sciences, University of Birjand, Birjand, Iran Ali Heidarianpour Department of Exercise Physiology, Faculty of Physical Education and Sport Sciences, Bu-Ali Sina University, Hamadan, Iran Hadis Abotalebian Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran Alireza Gharib Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran Nejat Kheiripour Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran Introduction: In this study, the effect of zinc sulfate (ZS) supplement and eight-week continuous training (CT) and interval training (IT) on liver oxidative stress of morphine-dependent rats following withdrawal syndrome (WS) were evaluated. Methods: Seventy Wistar rats were randomly divided into seven groups: control rats, withdrawing rats (WS), withdrawing rats receiving 9mg/kg ZS orally (WS+Z), withdrawing rats under CT (WS+CT), withdrawing rats under IT (WS+IT), withdrawing rats under CT and receiving 9mg/kg zinc sulfate (WS+Z+CT), withdrawing rats under IT and receiving 9mg/kg zinc sulfate (WS+Z+IT). Animals were addicted by 0.4g/l morphine sulfate in 21 days. Animals in the training groups ran on a treadmill and received ZS 5 days/week for 8 weeks. At the end of the study, oxidative stress in liver tissue and liver enzymes were measured by spectrophotometric and ELISA methods. Results: ZS supplement, CT/IT led to decrease DNA damage and malondialdehyde in comparison with morphine group. Also, ZS, CT and IT significantly elevated levels in superoxide dismutase, catalase activity, total antioxidant capacity and thiol groups in the liver of rats in comparison with morphine group. Additionally, it is observed that ZS and CT/IT made a significant reduction in aspartate aminotransferase levels in comparison to the morphine group. Conclusion: CT/IT with ZS because of its antioxidant effects has the potential to be used for decreased withdrawal syndrome complications.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Ginkgo biloba modulates hippocampal BDNF expression in a rat model of chronic restraint stress-induced depression 285 297 EN Seyed Abdolmajid Ayatollahi Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran shahrokh khoshsirat Hearing Disorders Research Center, Loghman HakimMedical Center, Shahid Beheshti University ofMedical Sciences, Tehran, Iran Ali Asghar Peyvandi Hearing Disorders Research Center, Loghman HakimMedical Center, Shahid Beheshti University ofMedical Sciences, Tehran, Iran Omidvar Rezaei Skull Base Research Center, Loghman Hakim Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran Fatemeh Zare Mehrjardi Neurobiomedical Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran Arezo Nahavandi Neuroscience Research Center, Department of Physiology, Iran University of Medical Sciences, Tehran, Iran Somayeh Niknazar Hearing Disorders Research Center, Loghman HakimMedical Center, Shahid Beheshti University ofMedical Sciences, Tehran, Iran Introduction: Mood disorders such as depression and anxiety disorders have been affecting a relatively high proportion of the world's population. Neuroplasticity hypothesis of depression proposes that lack of brain-derived neurotrophic factor (BDNF) can cause structural changes in the brain. The extract of Ginkgo biloba (Gb) leaves can restore much of the damage in the nervous system. We examined the antidepressant role of Gb extract (EGb 761) on BDNF expression modulation in the hippocampus of rats subjected to repeated restraint stress (RRS). Methods: Adult male rats were randomly divided into 10 groups: control, control-vehicle treated, stress, stress-vehicle treated, as well as three control and three experimental groups pretreated with EGb (15, 30, 60mg/kg, IP daily) for 21 days. They underwent restraint stress on a daily basis, 6 hours for 21 consecutive days. Weight changes, locomotor activity and forced swim test (FST) were employed to assess depressive-like symptoms. The serum corticosterone level was also measured by ELISA. Hippocampal BDNF DNA methylation and protein expression were assayed by methylation sensitive restriction enzymes (Real Time PCR) and Western-blotting respectively in all groups. Results: Pre-treatment with 30 and 60 mg/kg/day of Gb extract significantly attenuated depressive-like effects in the body weight, FST and serum corticosterone level in RSS rats compared to control groups. Further, it inhibited chronic stress-induced alterations in the hippocampal BDNF DNA methylation and protein expression. Conclusion: These findings suggest that Gb can induce an antidepressant role through its modulation effect on the hippocampal BDNF expression.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Network-based analysis reveals the potential involvement of proteasome subunit alpha-2 in tetralogy of Fallot 298 313 EN Hassan Karami Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran Maryam Moosavi Department of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran Afshin Derakhshani Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Ebrahim Miri-Moghaddam Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran Marlin Touma Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, United States Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Nazila Alizadeh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hossein Mashhadi Abdolahi Tabriz Health Services Management Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran Khalil Hajiasgharzadeh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Hossein Safarpour Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran Introduction: Tetralogy of Fallot (TOF) is the most common cyanotic form of congenital heart defects. However, there is no effective therapeutic approach and current therapies have limited curative efficacy. Moreover, the exact etiology of TOF has remained largely unknown. Improved understanding of molecular mechanisms can give an insight into TOF pathogenesis and development of therapeutic approaches. Methods: Here, we conducted a systematic study on the right ventricular myocardium of 24 infants (16 ToF/8 control) using weighted gene co-expression network analysis (WGCNA) to identify meaningful modules or candidate biomarkers. Results: Co-expression network analysis by WGCNA suggested that a highly preserved turquoise module with 2,493 genes and a P-value of 3×10-11 was significantly correlated to TOF. The top 5 hub genes of this module were PSMA2, MYL12A, C11ORF71, COMMD6, and CREG1. The result of turquoise module enrichment showed that the most correlation topic in biological processes and KEGG pathways were positive regulation of cardiac neural crest migration involved in outflow tract morphogenesis and positive regulation of neural crest cell differentiation. Also, we recognized 4 FDA-approved drug candidates for other indications could potentially use for the treatment of TOF patients through regulation of two hub genes of the co-expression network (PSMA2 and NDUFA4). Our findings also showed that the 13 experimentally validated microRNAs regulated the co-expression network through 5 hub genes. Conclusion: We systematically recognized co-expressed gene modules and hub genes associated with TOF progression, which offered insights into the mechanisms underlying TOF progression and some potential drugs for the treatment of TOF.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Hematological and histological effect of fractionated neem leaf extract in healthy Wistar rats 314 321 EN David Chibuike Ikwuka Department of Physiology, College of Medicine, University of Nigeria, Enugu, Nigeria Ed Nwobodo Department of Human Physiology, Faculty of Basic Medical Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria Bond U Anyaehie Department of Physiology, College of Medicine, University of Nigeria, Enugu, Nigeria Emmanuel l Umegbolu Department of General Outpatient, District Hospital Awgu, Enugu State, Nigeria Introduction: In recent years, the growing research towards new drugs has been targeted on plant-based drugs, and Neem (Azadirachta indica) is one of the plants that have been extensively researched for its diverse medicinal properties. The study aimed to determine the effects of neem on the hematological parameters (total white blood cells, neutrophil, monocyte and eosinophil counts) and histology of some organs of rats. Methods: Fifteen healthy male Wister rats divided into control (Nm0) and experimental groups (Nm11 and Nm22). Control group 1 (Nm0) was given 100mg/200g body weight of normal saline orally twice daily; experimental group 2 (Nm11), 100mg/200g body weight neem extract twice daily for 11 days and experimental group 3 (Nm22), 100mg/200g neem leaf extract twice daily for 22 days. Total number of white blood cells (WBC), lymphocytes, neutrophils, monocytes and eosinophils, packed cell volumes (PCV) and histological changes in the spleen, liver and kidneys were evaluated. Results: There were no significant differences in mean values of the hematological parameters (total WBC; PCV; neutrophils, lymphocytes, monocytes and eosinophils). We observed the central vacuolation and accumulation of lymphocytes in the spleen, hypertrophy of the central vein in the liver and shrinking of the glomeruli and accumulation of the lymphocytes in the kidney using hematoxylin and eosin staining following prolonged administration of neem extract (Nm22). Conclusion: Prolonged administration of neem affected the histology of some organs of the rats more than the hematological parameters.

Iranian Society of Physiology and Pharmacology Physiology and Pharmacology 24765236 24 4 2020 12 1 Antioxidant and antinociceptive effects of hydroalcoholic root extract of Asparagus officinalis L. 322 330 EN Mohammad Fathalipour Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Mohammad-Reza Delnavazi Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Omid Safa Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Nasser Zarifinia Department of Agricultural Engineering Research, Safiabad Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education and Extension Organization (AREEO), Dezful, Iran Bahare Rafiee Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran Introduction: Asparagus officinalis L. is a medicinal plant, which contains various natural bioactive phytochemicals with potential different pharmacological activities. The present study was designed to investigate the antioxidant and antinociceptive activities of the hydroalcoholic extract obtained from asparagus roots. Methods: The plant material was extracted using ethanol 70% and preliminary phytochemical analyses were carried out. The in vitro antioxidant effects of the plant extract were evaluated using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radicals and total reducing ability compared to the butylated hydroxytoluene (BHT) as a standard control. The antinociceptive effects were also assessed using formalin and tail-flick test in male Wistar rats. Results: The plant extract was relatively rich in flavonoids. The IC50 value for DPPH scavenging activity of the extract (1117.65±14.26 μg/ml) was significantly higher than that of BHT (64.35±4.09 μg/ml). The plant extract exerted a significantly lower total reducing ability compared to that of BHT. The extract exhibited a significant antinociceptive effect at the early stage of formalin test in the dose of 500mg/kg intraperitoneally. The results of tail-flick test also demonstrated antinociceptive effects compared to control in a dose-dependent manner. However, these antinociceptive activities were not comparable with morphine as a reference agent. Conclusion: A. officinalis roots extract demonstrated considerable antioxidant and antinociceptive activities and it might be attributed to its flavonoids content.