Concomitant administration of sitagliptin and rutin improves the adverse hepatic alterations in streptozotocin-induced diabetes mellitus in albino rats: an overview of the role of alpha smooth muscle actin

Background: Diabetes mellitus (DM), one of the commonest worldwide metabolic conditions, is believed to be associated with an imbalance between oxidants and antioxidants. Sitagliptin is an oral anti-hyperglycaemic drug that blocks dipeptidyl peptidase 4 (DPP4). Rutin is a polyphenolic natural flavonoid which has antioxidant and anti-proliferative activity. The aim of the present work is to elucidate the concomitant effect of sitagliptin and rutin on the deleterious alterations in the liver of experimentally induced diabetes in rats. Materials and methods: Fifty adult male albino rats, weighing 170-200 g were used. Rats were randomly divided into five groups (n = 10): group 1 (control group), the other four groups (groups II, III, IV and V) received a single i.p. injection of streptozotocin, 65 mg/kg body weight to induce diabetes; group II (diabetic), group III (diabetic and rutin administered), group IV (diabetic and sitagliptin administered), and group V (diabetic with sitagliptin and rutin concomitantly administered). Haematoxylin and eosin, Masson trichrome, periodic acid Schiff, immune-histochemistry: alpha-smooth muscle actin (alpha-SMA), histomorphometric analysis, liver enzymes and oxidants/anti-oxidants; malondialdehyde/glutathione and were done. Results: Distorted hepatic architecture, dilatation, congestion of sinusoids and central veins as well as cytoplasmic vacuolations were remarkable changes in the diabetic group. There was extravasation of blood, diffuse fibrous tissue formation, increase in the mean values of liver enzymes, oxidative markers and alpha-SMA expression in the same group. The aforementioned changes were ameliorated in groups III and IV. Concomitant administration of sitagliptin and rutin resulted in marked enhancement of these hepatic alterations. Conclusions: Combination of sitagliptin and rutin has an ameliorating effect on the hepatic deterioration induced by diabetes, which is better than either sitagliptin or rutin alone.