EMPAGLIFLOZIN MITIGATES OXIDATIVE STRESS AND LIVER ENZYMES ELEVATION IN A DEXAMETHASONE –INDUCED HEPATIC STEATOSIS RAT MODEL

Abstract

Empagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, is recognized as an oral hypoglycemic agent with potential hepatoprotective effect. While Empagliflozin shows hepatoprotective potential in metabolic NAFLD models, its specific efficacy against glucocorticoid-induced oxidative stress and liver injury remains insufficiently characterized. The present study aimed to investigate the impact of Empagliflozin (EMPA) on malondialdehyde (MDA) and liver enzymes in rats with Dexamethasone (DEX)–induced hepatic steatosis. Twenty-five male albino rats were divided into five groups (5 rats in each group): normal control group did not receive any medication; two DEX-induced groups one received  8 mg/kg/day and the other received 16 mg/kg/day for six days consecutively; another group received (EMPA 10 mg/kg/day + DEX 8 mg/kg /day) EMPA for six consecutive days prior to DEX with another six days during DEX administration without interruption; and the last group underwent the same process but with DEX16 mg/kg (EMPA 10 mg/kg/day + DEX 16 mg/kg /day). Blood samples were collected before the rats were sacrificed. Results revealed that the levels of the oxidative stress biomarker (MDA) were significantly elevated in DEX-treated groups compared with the control group. At a dose of 8 mg/kg DEX, the MDA level was 1.12 nmol/ml (P = 0.017), representing a 154% increase compared with the control. At a dose of 16 mg/kg DEX, the MDA level further increased to 1.44 nmol/ml (P < 0.001), corresponding to a 227% increase relative to the control group. EMPA 10mg/kg (group IV) reduced MDA level by 55.3%, which was statistically significant (P = 0.033), and group V reduced MDA level by 70.8% (P < 0.001), compared to groups II and III, respectively. Group five rats pretreated with EMPA led to a substantial statistically significant reduction in serum ALT (P < 0.001), with a decline by 57.8%, and serum AST declined by 54.6% (P < 0.001), serum ALP by 33.5% (P = 0.003), and serum LDH by 47.5% (P < 0.001), compared to the DEX 16 mg/kg group (group III).  In conclusion, Empagliflozin significantly ameliorated DEX-induced oxidative stress in albino rats and showed hepatoprotective effect through reduction of Dexamethasone-elevated liver enzymes and malondialdehyde. Further experimentation is required to explore the molecular mechanisms.