Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats.

Present study aimed to assess effect of pre-treatment with Mucuna pruriens seed extract and its bioactive molecule(s) on NMDAR and Tau protein gene expression in cerebral ischemic rodent model. Methanol extract of M. pruriens seeds was characterized by HPLC, and ß-sitosterol was isolated by flash chromatography. In vivo studies to observe the effect of pre-treatment (28 days) with methanol extract of M. pruriens seed and ß-sitosterol on the unilateral cerebral ischemic rat model. Cerebral ischemia induced by left common carotid artery occlusion (LCCAO) for 75 min (on day 29) followed by reperfusion for 12 h. Rats (n = 48) divided into four groups. GroupI (control,Untreated + LCCAO)-No pre-treatment + cerebral ischemia; GroupII(ß-sitosterol + Sham)-pre-treatment with ß-sitosterol, 10 mg/kg/day + sham-operated; GroupIII(ß-sitosterol + LCCAO)-pre-treatment with ß-sitosterol, 10 mg/kg/day + cerebral ischemia; GroupIV(methanol extract + LCCAO)-pre-treatment with methanol extract of M. pruriens seeds, 50 mg/kg/day + cerebral ischemia. Neurological deficit score was assessed just before sacrifice. Experimental animals were sacrificed after 12 h reperfusion. Brain histopathology was performed. Gene expression of NMDAR and Tau protein of left cerebral hemisphere (occluded side) was performed by RT-PCR. Results revealed that the neurological deficit score was lower in groups III and IV compared to group I. NMDAR and tau protein mRNA expression in left cerebral hemisphere were upregulated in Group I, downregulated in groups III and IV. Histopathology of left cerebral hemisphere (occluded side) in Group I showed features of ischemic brain damage. Groups III and IV, left cerebral hemisphere showed less ischemic damage compared GroupI. Right cerebral hemisphere showed no areas of ischemia-induced brain changes. Pre-treatment with ß-sitosterol and methanol extract of M. pruriens seeds may reduce ischemic brain injury following unilateral common carotid artery occlusion in rats.

Low oxygen microenvironment and cardiovascular remodeling: Role of dual L/N.type Ca2+ channel blocker.

OBJECTIVE: Patients exposed to chronic sustained hypoxia frequently develop cardiovascular disease risk factors to ultimately succumb to adverse cardiovascular events. In this context, the present study intends to assess the role of cilnidipine (Cil), a unique calcium channel blocker that blocks both L-type and N-type calcium channels, on cardiovascular pathophysiology in face of chronic sustained hypoxia exposure. MATERIALS AND METHODS: The study involved Wistar strain albino rats. The group-wise allocation of the experimental animals is as follows - Group 1, control (21% O2); Group 2, chronic hypoxia (CH) (10% O2, 90% N); Group 3, Cil + 21% O2; and Group 4, CH (10% O2, 90% N) + Cil (CH + Cil). Cardiovascular hemodynamics, heart rate variability, and endothelial functions (serum nitric oxide [NO], serum endothelial nitric oxide synthase [NOS3], and serum vascular endothelial growth factor [VEGF]) were assessed. Cardiovascular remodeling was studied by histopathological examination of the ventricular tissues, coronary artery (intramyocardial), and elastic and muscular arteries. Normalized wall index of the coronary artery was also calculated. RESULTS AND CONCLUSION: The results demonstrated altered cardiovascular hemodynamics, disturbed cardiovascular autonomic balance, increased levels of VEGF and NOS3, and decreased bioavailability of NO on exposure to chronic sustained hypoxia. The histopathological examination further pointed toward cardiovascular remodeling. Treatment with Cil ameliorated the cardiovascular remodeling and endothelial dysfunction induced by CH exposure, which may be due to its blocking actions on L/N-type of calcium channels, indicating the possible therapeutic role of Cil against CH-induced cardiovascular pathophysiology.

Effect of L-Ascorbic Acid on Nickel-Induced Alteration of Cardiovascular Pathophysiology in Wistar Rats.

Nickel, a widely used heavy metal is suspected as a cardiotoxic element. The aim of the present study was to assess the possible protective role of l-ascorbic acid on nickel-induced alterations of cardiovascular pathophysiology in male albino rats. Twenty-four albino rats (b.wt. 170-250 g) were randomized into four groups: control; l-ascorbic acid (50 mg/100 g b.wt., orally); NiSO4 (2.0 mg/100 g b.wt., i.p.); NiSO4 with l-ascorbic acid. Cardiovascular electrophysiology, serum and cardiac tissue malondialdehyde (MDA), nitric oxide (NO), ascorbic acid, serum α-tocopherol and serum vascular endothelial growth factor (VEGF) were evaluated. Histopathology of cardiac and aortic tissues was also assessed. NiSO4-treated rats showed a significant increase in heart rate, LF/HF ratio and blood pressure (SBP, DBP and MAP). A significant increase of serum MDA, NO and VEGF in NiSO4 treatment with a concomitant decrease of serum ascorbic acid and α-tocopherol as compared to their respective controls were also observed. Simultaneous supplementation of l-ascorbic acid with NiSO4 significantly decreased LF/HF ratio, BP and oxidative stress parameters, whereas ascorbic acid and α-tocopherol concentration was found to be increased. Histopathology of cardiac and aortic tissues showed nickel-induced focal myocardial hypertrophy and degeneration in cardiac tissue with focal aneurism in aortic tissues. Supplementation with l-ascorbic showed a protective action in both cardiac and aortic tissues. Results indicated the possible beneficial effect of l-ascorbic acid on nickel-induced alteration of the cardiovascular pathophysiology in experimental rats.

Subchronic hypoxia pretreatment on brain pathophysiology in unilateral common carotid artery occluded albino rats.

OBJECTIVE: This study was aimed to assess the effect of unilateral common carotid artery occlusion on brain pathophysiology in rats pretreated with subchronic hypoxia. MATERIALS AND METHODS: Rats (200 ± 20 g) were randomized into three groups: Group 1 served as sham, Group 2 were normoxic (21% O2 and 79% N2), and Group 3 were hypoxia preconditioned (10% O2 and 90% N2) for 21 days before left common carotid artery occlusion (LCCAO). The LCCAO was done for 75 min followed by reperfusion for 12 h. Neurological scores were recorded. Serum malondialdehyde (MDA) and nitric oxide (NO) levels at pre- and 12 h post-LCCAO were measured. Brain histopathological assessments were also done. RESULTS: Higher neurological deficits scores in Group 2 as compared to Group 3 rats were noticed. Serum MDA and NO levels at 12 h post-LCCAO in Group 2 rats showed significant elevation as compared to preocclusion levels. Group 3 rats did not show such elevations. On histopathology of left and right cerebral hemispheres of Group 1 (sham) did not show any specific changes. In Group 2 rats, the right cerebral hemisphere (nonoccluded) showed no areas of ischemia-induced brain changes, but in the left side (occlusive), there were features of ischemic brain damage including cerebral edema. In the case of Group 3 rats, there were less ischemic damages in the left occluded side as compared to the left side of the Group 2 rats. CONCLUSION: This study clearly demonstrates that subchronic hypoxia pretreatment can reduce ischemic brain injury by unilateral common carotid artery occlusion in rats.

Primary concept of nickel toxicity - an overview.

Toxic metals, including excessive levels of essential metals tend to change biological structures and systems into either reversible or irreversible conformations, leading to the derangement of organ functions or ultimate death. Nickel, a known heavy metal is found at very low levels in the environment. Nickel is available in all soil types and meteorites and also erupts from volcanic emissions. In the environment, nickel is principally bound with oxygen or sulfur and forms oxides or sulfides in earth crust. The vast industrial use of nickel during its production, recycling and disposal has led to widespread environmental pollution. Nickel is discharged into the atmosphere either by nickel mining or by various industrial processes, such as power plants or incinerators, rubber and plastic industries, nickel-cadmium battery industries and electroplating industries. The extensive use of nickel in various industries or its occupational exposure is definitely a matter of serious impact on human health. Heavy metals like nickel can produce free radicals from diatomic molecule through the double step process and generate superoxide anion. Further, these superoxide anions come together with protons and facilitate dismutation to form hydrogen peroxide, which is the most important reason behind the nickel-induced pathophysiological changes in living systems. In this review, we address the acute, subchronic and chronic nickel toxicities in both human and experimental animals. We have also discussed nickel-induced genotoxicity, carcinogenicity, immunotoxicity and toxicity in various other metabolically active tissues. This review specifically highlighted nickel-induced oxidative stress and possible cell signaling mechanisms as well.

Protective effects of Ethanolic Extract of Emblica officinalis (amla) on Cardiovascular Pathophysiology of Rats, Fed with High Fat Diet.

INTRODUCTION: Dietary high fat alters lipid profile and possibly induce sympatho-vagal imbalance. Emblica officinalis is found to be potential antioxidant and possibly counteract hyperlipidemia induced lipid peroxidation. AIM: To assess Ethanolic extract of Emblica Officinalis (EEO) as lipid lowering and cardiovascular protective agent against high dietary fat supplemented to experimental rats. Further to study a comparative analysis between EEO and atorvastatin on hyperlipidemia and cardiovascular integrity. MATERIALS AND METHODS: EEO was prepared and phytochemical analysis was done. Rats were divided into five groups, having six rats in each group as following; Group I-control (20% fat); Group II (+ EEO 100 mg/kg body wt); Group III (fed with high fat diet; 30% fat); Group IV (fed with high fat diet; 30% fat + EEO 100 mg/kg body wt) and Group V (fed with high fat diet; 30% fat + atorvastatin 4 mg/kg body wt). The treatments were continued for 21 days. Gravimetric parameters and electrophysiological parameters {Heart Rate (HR), sympatho-vagal balance} were recorded and lipid profiles of all the groups were measured. ANOVA, correlation and multiple regressions were done for analysis of data. RESULTS: Significant alteration in serum lipid profile was observed in rats fed with high dietary fat but supplementation of EEO was found to be reversible. Electrophysiological evaluation revealed altered HR and sympatho-vagal balance in high dietary fat fed rats (Group III) which indicate cardiac autonomic malfunctions which were found to be improved in Emblica officinalis supplemented group of rats (Group IV). Further, analysis has shown significant negative correlation between HDL/LDL and sympatho-vagal balance in all groups of rats which clearly indicate a role of dietary fat on sympatho-vagal balance. These results further corroborated with findings of histopathological study on myocardium and elastic artery. CONCLUSION: Observations from the study indicate a beneficial role of ethanolic extract of Emblica officinalis (amla) on dyslipidemia and cardiac autonomic functions in rats treated with high fat diet.

Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.

BACKGROUND: Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a few of indigenous plants which are routinely consumed by the people of north Karnataka in the diet. Studies on these plants showed some potential anti-diabetic efficacies. OBJECTIVES: To examine the effect of leaves extracts of Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling mechanisms in alloxan induced diabetic rats. METHOD: In vitro and in vivo tests on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1α and VEGF were conducted in alloxan induced diabetic rats supplemented with all the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio, baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic artery were evaluated in diabetic rats treated with L. scariola linn. RESULTS: Out of these three plant extracts, Lactuca scariola Linn supplementation showed significant beneficial effects on glucose homeostasis and oxygen sensing cell signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub chronic supplementation of Lactuca scariola Linn aqueous extracts showed significant improvement in sympatho-vagal balance in diabetic rats by increase of Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These results were also corroborated with myocardial and elastic artery histopathology of Lactuca scariola Linn supplemented diabetic rats. CONCLUSION: These findings indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell signaling mechanisms and cardio protective actions in alloxan - induced diabetic rats supplemented with Lactuca scariola Linn extracts.