Abstract:
Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis
and protect the liver until now. We intended to discover the empagliflozin’s (EMPA) hepatoprotective
efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK/SIRT-1 activity and
reducing HIF-1α. Rats were treated orally with EMPA (3 or 6 mg/kg) with TAA (100 mg/kg, IP)
thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia,
triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg/kg)
replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic
content of MDA, TNF-α, IL-6, NF-κB, or HIF-1α in a dose-dependent manner. Likewise, hepatic
photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or
6 mg/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly,
in rats given EMPA (3 or 6 mg/kg), the immunohistochemically of hepatic photomicrograph revealed
minimal stain of either α-SMA or caspase-3 compared to the TAA group. Therefore, we concluded
that EMPA possessed an antifibrotic effect by targeting AMPK/SIRT-1 activity and inhibiting HIF-1α.
The present study provided new insight into a novel treatment of liver fibrosis.
