Effect of Canagliflozin, an SGLT2 Inhibitor, in Comparison with Atorvastatin on Dexamethasone-Induced Hepatic Steatosis in Albino Rats

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is considered the most common liver disease all over the world. It causes metabolic and hepatic damage that can progress to cirrhosis and hepatocellular carcinoma. Objective: Our research pointed to study the preventive effects of canagliflozin (CANA) or atorvastatin (ATO) on dexamethasone-induced hepatic steatosis and dyslipidemia. Methods: Animals were grouped as; control group; DEX group; ATO/DEX-treated group; CANA/DE-treated group and ATO+CANA/DEX-treated group. Results: Significant elevations in GSH, SOD and CAT activities, while high significant decreases in serum GOT, GPT, ALP, urea, blood glucose, CK-MB, LDH, T.G, T.C, MDA and P.C levels were demonstrated in treated groups as compared to DEX group in the experimental periods. Also, significant reductions in SGPT, SGPT, ALP, CK-MB, LDH, T.C and T.G levels were detected in CANA/DEX group as compared to ATO/DEX group. All these results were confirmed with histopathological findings where the severe damages and fatty degeneration in both kidney and liver tissues developed by dexamethasone administration resolved by administration of atorvastatin alone or better with Canagliflozin. Conclusion: These results indicate that canagliflozin was as effective as atorvastatin or combination of both in reducing dyslipidemia and hepatic steatosis. The antioxidant and hypolipidemic effects of canagliflozin may be responsible for the beneficial effects.