Effect of Ursodeoxycholic Acid on Pentylenetetrazole Kindling and Kindling Induced Memory Impairment in Rat

BACKGROUND AND OBJECTIVE: Epilepsy is one of the common diseases of the brain that about 30-40% of patients with epilepsy experience recurent attacks due to drug resistance. Recently, the beneficial effects of Ursodeoxycholic acid on brain disorders have been considered. The aim of this study was to evaluate the effect of Ursodeoxycholic acid(UDCA)on the Pentylenetetrazole (PTZ) induced kindling, and related learning and memory impairments on Morris water maze. METHODS: This experimental study was done on 32 male Winstar rats divided into 4 groups. The first(n=7)and the second(n=9)groups have received three injections of 0.5 ml NaCl or 50 mg/kg of UDCA respectively and third(n=7) and fourth(n=9) groups have received fifteen injections of 0.5 ml NaCl or 50 mg/kg of UDCA respectively. All injections were given intraperitoneally(ip)(every 48 hours). In all groups, chemical kindling were started after third injections. Twenty-four hour after the last injection, spatial memory was investigated in the Morris water maze. FINDING: Fifteen injections of UDCA significantly reduced the seizure stage from 3.5±0.17 to 3.08±0.11 and duration of stages five from 12.37±1.21 to 8.43±1.09 and increased time to reach the stage five seizures from 1021.65±72.07 to 1252.41±49.63 as compared to control group. However, three injections of UDCA have no effect on the kindling process. However, three time administration of UDCA significantly increased reference memory from 18.72±1.2 s to 26.11±1.8 s. CONCLUSION: Ursodeoxycholic acid inhibits chemical kindling and improves kindling induced memory impairment

A Study on the Effects of Orally Administered Copper Sulfate on Learning ‎and Spatial Memory of Wistar Rats

BACKGROUND AND OBJECTIVE: Copper is one of the main micronutrients in the human body. Malfunction in copper homeostasis results in Menkes syndrome and Wilson’s disease, which are associated with complications such as seizure and impairments in learning and memory. Use of high copper concentrations can cause permanent damage to the cells and neurons. The aim of this study was to examine the toxic effects of orally administered copper sulfate on rats’ learning in Morris water maze. METHODS: In this experimental study, 39 Wistar rats were divided into male (n=21) and female (n=18) groups. These two groups were each randomly divided into three sub-groups. The control group received distilled water, while the other two groups were administrated 1 and 1.5 mM of copper sulfate, dissolved in distilled water for a period of one month. After this period, the Morris water maze was incorporated to evaluate the spatial memory of rats. FINDINGS: In male rats, copper sulfate, which was added to drinking water, made no significant changes in the distance traveled to find the platform (24.09%±3.01 in the control group, 26.06%±2.95 in the 1 mm copper sulfate group, and 25.68%±1.82 in the 1.5 mM copper sulfate group), the time spent to find the platform (23.93±2.87 in the control group, 25.54±3.47 in the 1 mM copper sulfate group, and 25.33±1.92 in the 1.5 mM copper sulfate group), or the swimming speed. The comparison of female groups showed that 1 and 1.5 mM concentrations of copper sulfate could not cause any significant impairments in learning of rats. CONCLUSION: The results showed that the addition of copper sulfate to drinking water have no detrimental impacts on the memory or learning of male and female rats

RISK pathway is involved in oxytocin postconditioning in isolated rat heart

The reperfusion injury salvage kinase (RISK) pathway is a fundamental signal transduction cascade in the cardioprotective mechanism of ischemic postconditioning. In the present study, we examined the cardioprotective role of oxytocin as a postconditioning agent via activation of the RISK pathway (PI3K/Akt and ERK1/2). Animals were randomly divided into 6 groups. The hearts were subjected under 30 minutes (min) ischemia and 100 min reperfusion. OT was perfused 15 min at the early phase of reperfusion. RISK pathway inhibitors (Wortmannin; an Akt inhibitor, PD98059; an ERK1/2 inhibitor) and Atosiban (an OT receptor antagonist) were applied either alone 10 min before the onset of the ischemia or in the combination with OT during early reperfusion phase. Myocardial infarct size, hemodynamic factors, ventricular arrhythmia, coronary flow and cardiac biochemical marker were measured at the end of reperfusion. OT postconditioning (OTpost), significantly decreased the infarct size, arrhythmia score, incidence of ventricular fibrillation, Lactate dehydrogenase and it increased coronary flow. The cardioprotective effect of OTpos was abrogated by PI3K/Akt, ERK1/2 inhibitors and Atosiban. Our data have shown that OTpost can activate RISK pathway mostly via the PI3K/Akt and ERK1/2 signaling cascades during the early phase of reperfusion. © 2016 Elsevier Inc

Lack of association between coding region of KCNE2 gene and the congenital long QT syndrome in an Iranian population

Introduction: Congenital long QT syndrome (LQTS) is a cardiac disorder characterized by QT interval prolongation at basal ECG. Different LQTS genes encode ion channel subunits or proteins involved in regulating cardiac ionic currents. Long QT syndrome type 6 (LQT6) is caused by mutation in the KCNE2 gene. Our research aimed to analyze genetic variants of KCNE2 gene causing the disease in Iranian population. Methods: Twenty nine patients consented for participation in the study. They were diagnosed based on Schwartz’s criteria. After DNA extraction from peripheral blood cells, two exons of the KCNE2 gene were amplified. Afterwards, PCR-SSCP was carried out for screening the possible mutated gene variants. As the last verification step, direct sequencing was done to determine the sequence. Results: All samples were detected by PCR-SSCP and sequenced. None of the patients had the mutation in the KCNE2 gene. Conclusion: Investigating a genetic variant associated with LQTS, in Iranian patients clinically diagnosed with LQT6, no association was found between the disease and KCNE2 gene. Other previously identified genes, especially the major genes, should be considered for further investigation. © 2016, Iranian Society of Physiology and Pharmacology. All rights reserved

The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart

Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion. Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase. © 2018 Elsevier Inc

Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart

Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats� hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria. © 2020 Elsevier B.V