Effects of atorvastatin and metformin on development of pentylenetetrazole-induced seizure in mice

Biochemistry; Toxicology; Pharmacology; Clinical Toxicology; Medical Ethics; Atorvastatin; Metformin; Pentylenetetrazole kindling; seizure © 2020 Recent studies have shown that statins and Metformin may have beneficial effects on seizure through different mechanisms. In the current study, we investigated whether Metformin, Atorvastatin, and concomitant uses of them have beneficial effects on pentylenetetrazole (PTZ)-induced kindling. Adult male C57BL/6 mice were randomly divided into four experimental groups with seven mice in each group. Group 1, control group; group 2, received Metformin (200 mg/kg, i.p); group 3, received Atorvastatin (10 mg/kg, i.p.); group 4, received Atorvastatin (10 mg/kg, i.p.) plus Metformin (200 mg/kg, i.p.). Twenty minutes after injection of the mentioned drugs, the experimented mice received 37/5 mg/kg of PTZ intraperitoneally on alternating days. Then the convulsive behavior signs were evaluated for 20 min after each PTZ injection. There were significant differences in the stage 2 latency parameter among group 2 (p = 0.033, F = 8.46)/group 3 (p = 0.032, F = 10.42)/group 4 (p = 0.008, F = 24.57) as compared to the control group, while no significant differences were found comparing only group 2,3, and 4 with eachother excluding the control group. Pretreatment with Atorvastatin (p = 0.002, F = 33), Atorvastatin + Metformin (p = 0.006, F = 20.77), and Metformin alone increased stage 5 latency as compared to the PTZ group, significantly. Also, our results have shown that pretreatment with Atorvastatin (p = 0.013, F = 14.48), Metformin (p = 0.015, F = 16.67), and concomitant usage of them significantly decreased stage 5 duration as compared to the control group. Our findings clearly demonstrate that concomitant use of Metformin and Atorvastatin has no more protective effect against the development of kindling as compare to these drugs alone. Thus, we concluded that, these drugs may inhibit kindling via a similar mechanism and we suggested that it is probably through regulation of autophagy. © 202

Effects of Raspberry Fruit (Rubus anatolicus (focke) foke ex hausskn) Hydroalcoholic Extract on Blood Glucose, Lipid Profile and Oxidative Stress Markers in Streptozotocin-diabetic Rats

Background and Objectives: Diabetes is one of the most common endocrine disorders worldwide. Rubus anatolicus is rich in polyphenolic compounds that can protect individual from various chronic diseases such as diabetes. This study was carried out to investigate effects of hydroalcoholic extract of raspberry fruit Rubus anatolicus (focke) on blood glucose levels, lipid profiles and oxidative stress markers in streptozotocin-induced diabetic rats. Materials & Methods: In this study, 32 male Wistar rats weighing 150�200 g were used. Diabetes was induced in rats using streptozotocin and diabetic animals were then treated with raspberry fruit hydroalcoholic extract for 14 days. Rats were anesthetized using xylazine and ketamine mixture and sacrificed. Then, whole blood samples were collected from the animal hearts to assess their serum glucose levels, lipid profiles and oxidative markers. The p-value < 0.05was considered as significant. Results: Results of the present study showed that raspberry fruit extracts significantly decreased serum glucose levels, triglycerides, cholesterol, low-density lipoproteins and malondialdehyde levels in diabetic rats, compared to the diabetic control rats (p < 0.05). Moreover, serum low-density lipoproteins level, total antioxidant capacity and superoxide dismutase activity significantly increased in diabetic rats, compared to diabetic control rats (p < 0.05). Conclusion: The present study showed that fruit extract raspberry included good effects on blood glucose levels, lipid profiles and oxidative stress conditions in diabetic rats. © 2022, National Nutrition and Food Technology Research Institute. All rights reserved

Frequency-dependent electrophysiological properties of concealed slow pathway of isolated rabbit atrioventricular node preparation after fast pathway ablation in a functional model

Introduction: Intranodal pathways of atrioventricular (AV) node play a vital role in the delay of conduction time in response to various atrial inputs. The present study was aimed to determine the frequency-dependent electrophysiological properties of concealed slow pathway according to a functional model of isolated rabbit atrioventricular node preparation after fast pathway ablation. Methods: Experiments were carried out in rabbit isolated heart AV-nodal preparations (N=8) by superfused/perfused mode. Extracellular recording was carried out from transitional cells of posterior and anterior extension of AV-node and upper part of atrium and its bundle. Unipolar silver electrode (100 μm) and direct voltage (100-110 V) was applied to create AV-nodal fast pathway ablation. Results: Minimum conduction time (AHmin) was significantly increased after fast pathway ablation (p<0.05). Fast pathway ablation had no significant impact on fatigue phenomenon but significantly reduced facilitation value (p<0.05). Rate-dependency properties of concealed slow pathway were explained according to functional nodal model. Conclusion: The mathematical functional model accurately simulated frequency-dependent electrophysiological properties of concealed slow pathway after fast pathway ablation, but some modifications are necessary for accurate prediction of nodal behavior in various cycle lengths and in arrhythmia. Concealed slow pathway may be considered as a potential electrophysiological substrate of fatigue and facilitation phenomenon

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