| Autor: |
ElBaset MA; Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, Egypt., Salem RS; Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt., Ayman F; Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt., Ayman N; Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt., Shaban N; Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt., Afifi SM; Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt., Esatbeyoglu T; Department of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany., Abdelaziz M; Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt., Elalfy ZS; Pathology Department Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, Egypt. |
| Abstrakt: |
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. |
