Comparative Mitigating Effects of Bioactive of Pleurotus tuber-regium and Empagliflozin on Hepatic Oxidative Damage in Type 2 Diabetic Rats

Abstract

Aims: This study evaluates the hepatoprotective and antioxidant potential of the ethanolic extract of in high-fat-streptozotocin-induced diabetic Wistar rats. Pleurotus tuber-regium is an oyster mushroom rich in essential nutrients and possesses anti-inflammatory, hypoglycemic, and hypocholesterolemic properties. Study Design: Type 2 diabetes was induced in rats by a single intraperitoneal injection of 40mg/kg body weight of streptozotocin; rats with >200 mg/dl were grouped for immediate intervention to mitigate oxidative stress.  Oral doses for 7 days of ethanolic extract of Pleurotus tuber-regium (200mg/kg, 400mg/kg, and standard drug Empagliflozin (20 mg/kg, 40 mg/kg) were administered.  Blood samples were collected using sterile EDTA bottles via the retro-orbital plexus, and serum was obtained to analyse for hepatic biomarkers. Place and Duration of Study: The experimental animals were bred in the Physiology department, faculty of Medical Sciences, University of Lagos, Akoka, Lagos, between January 7 and January 30, 2025. Methodology: Thirty-six male Wistar albino rats (120-150 g) were used for this experiment. Type 2 diabetes was induced in male Wistar rats via a single intraperitoneal injection of 40 mg/kg body weight streptozotocin, following a high-fat diet. Diabetic rats with fasting blood glucose levels >200 mg/dl were grouped and treated orally for seven days with ethanolic extract of P. tuber-regium at doses of 200 mg/kg and 400 mg/kg, while standard drug (Empagliflozin) was administered at 20 mg/kg and 40 mg/kg. Blood was collected via the retro-orbital plexus for hepatic function analysis alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver tissues were harvested, homogenized, and analyzed for antioxidant enzymes, catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation marker malondialdehyde (MDA). Results: Untreated diabetic rats showed significantly elevated AST and ALT levels, reduced antioxidant enzyme activities (SOD, CAT, GSH), and increased MDA levels, indicating hepatic oxidative stress. Treatment with P. tuber-regium extract significantly (p<0.05) improved antioxidant enzyme levels and reduced lipid peroxidation in a dose-dependent manner. ALP showed only mild alterations, suggesting early hepatic stress. These findings indicate biochemical recovery in liver function following extract administration. Conclusion: Ethanolic extract of Pleurotus tuber-regium demonstrated hepatoprotective and antioxidant effects in diabetic rats, likely mediated through its bioactive compounds. The extract mitigated oxidative hepatic injury and improved antioxidant status.