Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats

Role of AMPK/SIRT-1/HIF-1α Pathway in Halting Liver Fibrosis

authored by

Marwan A. ElBaset, Rana S. Salem, Fairouz Ayman, Nadeen Ayman, Nooran Shaban, Sherif M. Afifi, Tuba Esatbeyoglu, Mahmoud Abdelaziz, Zahraa S. Elalfy

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.

Organisation(s)

Institute of Food Science and Human Nutrition
Molecular Food Chemistry and Food Development

External Organisation(s)

National Research Center, Cairo
October 6 University
University of Sadat City

Type

Article

Journal

Antioxidants

Volume

11

ISSN

2076-3921

Publication date

11.2022

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Food Science, Physiology, Biochemistry, Molecular Biology, Clinical Biochemistry, Cell Biology

Electronic version(s)

https://doi.org/10.3390/antiox11112152 (Access: Open)