Hypoglycemic, antilipidemic and antioxidant effects of valproic acid in alloxan-induced diabetic rats

This study was designed to investigate the hypoglycemic, antilipidemic and antioxidant effects of valproic acid (VA) in alloxan-induced diabetic rats. VA (100, 300 and 600mg/kg p.o.) and insulin (17IU/kg s.c.) were administered once daily for 21 days. Fasting blood glucose level was determined at 7...

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Bibliographic Details
Published in:	European journal of pharmacology Vol. 762; pp. 174 - 183
Main Authors:	Akindele, Abidemi J., Otuguor, Edafe, Singh, Dhirendra, Ota, Duncan, Benebo, Adokiye S.
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 05-09-2015
Subjects:	Alloxan Animals Antilipidemic Antioxidant Antioxidants - pharmacology Antioxidants - therapeutic use Blood Glucose - metabolism Body Weight - drug effects Calcium - metabolism Cytosol - drug effects Cytosol - metabolism Diabetes Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Drinking - drug effects Hydrogen Peroxide - metabolism Hypoglycemic Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Hypolipidemic Agents - pharmacology Hypolipidemic Agents - therapeutic use Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - metabolism Kidney - drug effects Kidney - metabolism Kidney - pathology Lipids - blood Liver - drug effects Liver - metabolism Liver - pathology Male Malondialdehyde - metabolism Organ Size - drug effects Rats Rats, Wistar Valproic acid Valproic Acid - pharmacology Valproic Acid - therapeutic use Alloxan Hypoglycemic Diabetes Valproic acid Antioxidant Antilipidemic
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Summary:	This study was designed to investigate the hypoglycemic, antilipidemic and antioxidant effects of valproic acid (VA) in alloxan-induced diabetic rats. VA (100, 300 and 600mg/kg p.o.) and insulin (17IU/kg s.c.) were administered once daily for 21 days. Fasting blood glucose level was determined at 7 days interval. On day 21, blood samples were collected for assay of serum biochemical parameters (total protein, creatinine, urea, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), and low density lipoprotein (LDL)). Kidneys and livers were harvested for antioxidant indices and histopathological examination. In diabetic rats, VA produced a dose and day-dependent reduction in glucose level. Peak effect (52.79% reduction; P<0.001) was produced at the dose of 600mg/kg on day 21. In normoglycemic rats, VA (600mg/kg) caused significant reduction (P<0.05) in blood glucose level on days 1 and 21 with 16.38% and 15.63% reductions respectively. In diabetic rats, VA significantly reduced the level of catalase (CAT) and malondialdehyde (MDA) in the kidney, and increased the level of superoxide dismutase, CAT and glutathione peroxidase with reduction in MDA in the liver compared to diabetic control, especially at the dose of 600mg/kg. VA (600mg/kg) generally increased the level of HDL and reduced the levels of TG, LDL, TC, AST, ALT, ALP, bilirubin, creatinine and urea compared with diabetic control. The findings in this study suggest that VA possess beneficial antidiabetic effects.
ISSN:	0014-2999 1879-0712
DOI:	10.1016/j.ejphar.2015.05.044