Telmisartan Attenuates Experimental Liver Fibrosis Through Suppression Of Hepatic Stellate Cell Activation And Tgf-Β/Smad Signaling

Abstract

Background and Aim
Liver fibrosis, characterized by the excessive deposition of extracellular matrix (ECM) due to recurrent damage, is a dynamic wound-healing response that may progress to cirrhosis. It represents a significant global health issue, serving as a critical determinant in the progression of chronic liver disorders and correlating with heightened liver-related morbidity and mortality. This study aims to investigate the therapeutic effects of Telmisartan on liver fibrosis.
Methods
Thirty-two male Wistar rats were utilized to examine hepatic fibrosis and the impact of Telmisartan administration. Fibrosis was induced via intraperitoneal injections of carbon tetrachloride (CCL4) over eight weeks. The rats were categorized into four groups: a vehicle control, a fibrosis control, and two treatment groups administered low and high dosages of Telmisartan. Post-treatment evaluations included serum tests for liver enzymes and oxidative stress indicators. Histological examinations of hepatic tissues were conducted to assess inflammation and collagen accumulation. Additionally, hepatic stellate cells (HSCs) were extracted and cultured to undergo functional assays evaluating proliferation, migration, and collagen synthesis.
Results
Our research indicates that Telmisartan exerts a robust, dose-dependent antifibrotic effect on liver fibrosis through multiple mechanisms: it diminishes hepatocellular injury, reduces oxidative stress, inhibits HSC activation, and obstructs profibrotic signaling pathways. The high dose (10 mg/kg) consistently surpassed the low dose (5 mg/kg), achieving a reduction in fibrotic area of up to 65.6% and significant restoration of antioxidant enzyme activity toward near-normal levels
Conclusion
This study demonstrates the significant antifibrotic effects of Telmisartan in a rat model of liver fibrosis.These effects are mediated through the mitigation of hepatocyte injury, alleviation of oxidative stress,and suppression of hepatic stellate cell activation.