Cilnidipine and magnesium sulfate supplement ameliorates hyperglycemia, dyslipidemia and inhibits oxidative-stress in fructose-induced diabetic rats

The study was designed to evaluate the safety and efficacy of cilnidipine (CLN) and Mg-supplementation in fructose-induced diabetic rats. Diabetes was induced into male Wister rats by feeding fructose (10% solution) in drinking water for 8 weeks. Diabetic rats were subjected for the oral administration of CLN1 (1 mg/kg/day) and CLN10 (10 mg/kg/day), and/or methyl cellulose (0.5%) as vehicle for 28 days. After 14 days of CLN treatment, MgSO(4) (1%) was added to CLN1 and CLN10 groups for another 14 days. Age-matched healthy rats were used as normal control. After 28 days body weights were measured and organ weight to body ratio was calculated. Serum samples were analysed for fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), uric acid, lipid profiles, tri-iodothyronine (T(3)) and thyroid stimulating hormone (TSH), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), creatine phosphokinase myocardial-band (CK-MB), creatinine, albumin, electrolytes. Oral glucose tolerance tests (OGTT), liver histopathology and in-vivo antioxidant activities were also performed. The survival rate in diabetic rats was 100% after the oral administration of CLN, Mg-supplement and/or vehicle. A significant reduction in FBS levels and improvement in OGTT were observed in CLN10, CLN1+Mg and CLN10 + Mg groups after 28 days. Further, the treatment ameliorated serum lipid profile, uric acid, and albumin levels. The groups CLN10 and CLN10 + Mg improved HbA1c, liver glycogen, creatinine, T(3), TSH levels and electrolytes in diabetic rats. Moreover, liver from CLN10 and CLN10 + Mg groups showed preservation of cellular architecture as evidenced by attenuation of inflammatory markers SGPT, SGOT and CK-MB; and the levels of superoxide dismutase (SOD), catalase (CAT), glutathione, malondialdehyde (MDA), markers of oxidative stress were significantly improved. CLN exerted prominent effects in the amelioration of hyperglycemia, dyslipidemia and reduced hepatic inflammation; and Mg-supplementation might have some beneficial effects on diabetic complications and oxidative stress in fructose-induced diabetic rats.