Arvindkumar E. Ghule

Therapeutic role of curcumin in prevention of biochemical and behavioral aberration induced by alcoholic neuropathy in laboratory animals

Painful peripheral neuropathy induced by chronic ethanol consumption is a major medico-socioeconomical problem. The objective of present investigation was to study the effect of curcumin (20, 40 and 80mg/kg; p.o.) in alcohol-induced neuropathy in rats. Ethanol (35% v/v, 10g/kg; p.o.) was administered for 10 weeks which showed a significant decrease in thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocity. It caused enhanced malondialdehyde, oxidative-nitrosative stress, total calcium levels, inflammatory mediators (TNF-α and IL-1β levels) along with DNA damage. Co-administration of curcumin and α-tocopherol for 10 weeks significantly and dose-dependently improved nerve functions, biochemical as well as molecular parameters and DNA damage in sciatic nerve of ethanol treated rats. Hence, it was concluded that curcumin is of potent therapeutic value in the amelioration of alcoholic neuropathy in rats and acts by inhibition of pro-inflammatory mediators like TNF-α and IL-1β.

Effect of hydroalcoholic extract of Hibiscus rosa sinensis Linn. leaves in experimental colitis in rats.

OBJECTIVE To elucidate the ameliorative effect of hydroalcoholic extract of leaves of Hibiscus rosa sinensis (HRS) in acetic acid induced experimental colitis in male wistar rats. METHODS The animals were administered with 2 mL acetic acid (4%) via intra rectal. The animals were divided into various treatment groups (n=6). Prednisolone was used as standard drug and HRS was administered at a dose of 50, 100 and 200 mg/kg p.o. The control group of animals received 1 mL of vehicle (distilled water). Ulcer area, ulcer index, spleen weight, colon weight to length ratio, macroscopic score, haematological parameters, colonic superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and histological changes were recorded after the treatment regimen of 11 days. RESULTS Intrarectal instillation of acetic acid caused enhanced ulcer area, ulcer index, spleen weight, colon weight to length ratio, colonic MPO, MDA, NO and TNF-α It caused significant decreased level of SOD and GSH. Pretreatment with HRS for 7 days exhibited significant effect in lowering of oxidative stress, colonic NO, TNF-α and elevation of SOD and GSH at a dose of 100 and 200 mg/kg in acetic acid induced colitis. CONCLUSIONS The present investigation demonstrates HRS is of potent therapeutic value in the amelioration of experimental colitis in laboratory animals by inhibiting the proinflammatory mediator like NO and TNF-α.

Elucidation of molecular mechanism involved in neuroprotective effect of Coenzyme Q10 in alcohol-induced neuropathic pain

The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol‐induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K‐ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative–nitrosative stress, TNF‐α, IL‐1β, and IL‐4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α‐tocopherol (100 mg/kg) combination‐treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α‐tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido‐nitrosative stress, release of pro‐inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination.

Dietary flaxseed oil and fish oil modulates expression of antioxidant and inflammatory genes with alleviation of protein glycation status and inflammation in liver of streptozotocin-nicotinamide induced diabetic rats.

Beneficial effects of dietary flaxseed oil or fish oil on streptozotocin-nicotinamide induced diabetic rats were investigated. Rats were divided into three diabetic and three non-diabetic groups and received control, flaxseed oil or fish oil diets (10%w/w). Both diets reduced blood glucose, TBARS and hepatic NO. The extent of glycation measured in terms of glycated albumin and hemoglobin was reduced significantly with both diets. Flaxseed oil diet up-regulated hepatic catalase (CAT) (activity and expression), superoxide dismutase (SOD) (activity and expression) and glutathione peroxidase (GPx) expression. Fish oil diet up-regulated hepatic CAT (activity and expression), paraoxonase-1 (PON-1) expression and down-regulated heme oxygenase-1 (HO-1) expression. Furthermore, both diets down-regulated the expression of hepatic inflammatory genes TNF-α, IL-6, MCP-1, INF-γ and NF-κB. These results were supported by histopathological observations which showed better tissue preservation in both the diets. Thus, both the diets proved to be beneficial in preventing tissue injury and alleviating diabetic insults in the livers of STZ-NIC diabetic rats.

Oral l-glutamine increases active GLP-1 (7-36) amide secretion and improves glycemic control in stretpozotocin–nicotinamide induced diabetic rats

L-glutamine is a non-essential amino acid. It decreased blood sugar, stimulated insulin secretion in type 2 diabetic patients. The objective of the present investigation was to evaluate L-glutamine increases glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide (STZ-NTM) induced diabetic Sprague Dawley rats. Molecular docking study was performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100 mg/kg, i.p.) followed by 20 min after administration of streptozotocin (55 mg/kg, i.p.). The rats were divided into; I - nondiabetic, II - diabetic control, III - sitagliptin (5 mg/kg, p.o.), IV - L-glutamine (250 mg/kg, p.o.), V - L-glutamine (500 mg/kg, p.o.) and VI - L-glutamine (1000 mg/kg, p.o.). The L-glutamine and sitagliptin treatment was 8 week. Plasma glucose was estimated every week. Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagon GLP-1, plasma and pancreatic insulin, histology of pancreata and biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8 week. In acute study, the rats were divided into I - glucose (2.5 g/kg, p.o.), II - sitagliptin (5 mg/kg, p.o.), III - L-glutamine (250 mg/kg, p.o.), IV - L-glutamine (500 mg/kg, p.o.) and V - L-glutamine (1000 mg/kg, p.o.). Plasma glucose, active GLP-1 (7-36) amide concentration and insulin levels were measured after glucose loading. The docking data indicated that l-glutamine bind to the GLP-1 receptor. L-glutamine decreased plasma glucose, increased plasma and pancreatic insulin, increased plasma and colonic active GLP-1 (7-36) amide secretion as well as decreased oxidative stress in streptozotocin-nicotinamide induced diabetic rats.

L-Glutamine Supplementation Prevents the Development of Experimental Diabetic Cardiomyopathy in Streptozotocin-Nicotinamide Induced Diabetic Rats

The objective of the present investigation was to evaluate the effect of L-glutamine on cardiac myopathy in streptozotocin-nicotinamide induced diabetic rats. Diabetes was induced in overnight fasted Sprague Dawely rats by using intraperitonial injection of streptozotocin (55 mg/kg). Nicotinamide (100 mg/kg, i.p.) was administered 20 min before administration of streptozotocin. Experimental rats were divided into Group I: non-diabetic control (distilled water; 10 ml/kg, p.o.), II: diabetic control (distilled water, 10 ml/kg, p.o.), III: L-glutamine (500 mg/kg, p.o.) and IV: L-glutamine (1000 mg/kg, p.o.). All groups were diabetic except group I. The plasma glucose level, body weight, electrocardiographic abnormalities, hemodynamic changes and left ventricular contractile function, biological markers of cardiotoxicity, antioxidant markers were determined after 4 months after STZ with nicotinamide injection. Histopathological changes of heart tissue were carried out by using H and E stain. L-glutamine treatment improved the electrocardiographic, hemodynamic changes; LV contractile function; biological markers; oxidative stress parameters and histological changes in STZ induced diabetic rats. Results from the present investigation demonstrated that L-glutamine has seemed a cardioprotective activity.

Effect of ethanolic extract of seeds of Linum usitatissimum (Linn.) in hyperglycaemia associated ROS production in PBMNCs and pancreatic tissue of alloxan induced diabetic rats

Abstract Objective To evaluate the effect of ethanolic extract of seeds of Linum usitatissimum (EELU) in hyperglycemia associated reactive oxygen species (ROS) production in peripheral blood mononuclear cells (PBMNCs) and pancreatic antioxidant enzymes in alloxan induced diabetic rat. Methods Diabetes was induced in male Wistar rats by alloxan (120 mg/kg, i.p. ). After acute and subacute treatment serum glucose was determined. Oral glucose tolerance test (OGTT) was performed in EELU pretreated animals. ROS production in PBMNCs and pancreatic antioxidant enzymes were measured in alloxan induced diabetic rat. Results Our results showed that, treatment of EELU (200 and 400 mg/kg) significantly reduced serum glucose level in acute and subacute study. The antihyperglycaemic effects of EELU showed onset at 4th h ( P P P P P P P P Conclusions It is concluded from the investigation that EELU showed antihyperglycaemic effect mediated through inhibition of ROS level in PBMNCs and preservation of endogenous antioxidant enzymes in pancreatic tissue in alloxan induced diabetic rat.

Cycloart-23-ene-3β, 25-diol stimulates GLP-1 (7–36) amide secretion in streptozotocin–nicotinamide induced diabetic Sprague Dawley rats: A mechanistic approach

In previous study, we have reported cycloart-23-ene-3β, 25-diol is an active antidiabetic constituent isolated from stem bark of Pongamia pinnata (Linn.) Pierre. The objective of the present investigation was to evaluate cycloart-23-ene-3β, 25-diol stimulates glucagon like peptide-1 (GLP-1) (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats. Molecular docking studies were performed to elucidate the molecular basis for GLP-1 receptor agonistic activity. Type 2 diabetes was induced in overnight fasted Sprague Dawley rats pre-treated with nicotinamide (100mg/kg, i.p.) followed by administration of streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into following groups; I- non-diabetic, II- diabetic control, III- sitagliptin (5mg/kg, p.o.), IV- cycloart-23-ene-3β, 25-diol (1mg/kg, p.o.). The cycloart-23-ene-3β, 25-diol and sitagliptin treatment was 8 week. Plasma glucose was estimated every week (week 0 to week 8). Body weight, food and water intake were recorded daily. Glycosylated haemoglobin, lipid profile, plasma and colonic active (GLP-1) (7-36) amide, mRNA expression of proglucagnon GLP-1, plasma and pancreatic insulin, histology of pancreata as well as biomarkers of oxidative stress (superoxidase dismutase, reduced glutathione, malondialdehyde, glutathione peroxidase, glutathione S transferase) were measured after 8th week treatment. In acute study, active GLP-1 (7-36) amide release, plasma glucose and insulin were measured during oral glucose tolerance test. The docking data clearly indicated cycloart-23-ene-3β, 25-diol bind to the GLP-1 receptor. It decreased plasma glucose level, increased plasma and pancreatic insulin level as well as increased plasma and colonic active GLP-1 (7-36) amide secretion in streptozotocin-nicotinamide induced diabetic Sprague Dawley rats.