Histological study on the effect of canagliflozin-metformin hcl extended - release (invokamet xr) on the liver of normal and experimentally induced diabetes mellitus in adult male albino rats

Abstract

Background: Diabetes mellitus represents a global health problem. It is considered the third greatest killer due to its complications. Invokamet XR is a recent single oral combination of canagliflozin plus metformin HCL used in treatment of type 2 diabetes mellitus (T2DM). Objective: To evaluate the effect of Invokamet XR on the liver of normal and experimentally induced T2DM in adult male albino rats. Materials and Methods: Thirty five adult male albino rats weighing 160-180g were categorized equally into five groups. (G1) control group; (G2) Invokamet XR group treated orally with 200 mg/kg b.w/ rat /day; (G3) buffer control group, given a single intraperitoneal (i.p.) injection of 0.1M sodium citrate buffer (0.5 ml/rat); (G4) diabetic group and (G5) diabetic group treated with Invokamet XR. T2DM was induced in G4 and G5, by a single i.p injection of nicotinamide (NA) (110 mg/kg b.w) followed by streptozotocin (STZ) (35 mg/kg b.w) 15 minutes later. At the end of the experiment (3 weeks) blood was collected for biochemical analysis of AST, ALT & ALP enzymes. Liver samples were taken for light microscopic examination. The body weight and fasting blood glucose level, in addition to histomorphometrical and statistical analysis were done. Results: The present study revealed that T2DM induced a significant increase in liver enzymes, loss of the normal histological structure as; congestion and dilatation of the blood vessels; mononuclear cell infiltration; hepatocyte vacuolation with pyknotic nuclei. Invokamet XR induced slight improvement in these changes in the diabetic animals. Conclusion: Invokamet XR has a potent anti-hyperglycemic effect but it has a slight protective action on the biochemical and histological changes induced by T2DM that might be due to an improvement in the blood glucose level and a reduction in the complications associated with diabetes.