Tamsulosin regulates antifibrotic effects in thioacetamide-induced liver damage and ameliorates portal hypertension.

Liver cirrhosis is one of the leading causes of mortality worldwide, with portal hypertension being the initial sign of decompensation. Recent studies in animal models of liver fibrosis have proposed various treatments that reduce stellate cell activity, with adrenergic antagonists having an impact. This study evaluated the effect of tamsulosin as a potential treatment to reduce fibrosis and portal hypertension in a rat model of cirrhosis, without affecting the regenerative capacity of hepatocytes. In vitro, viability, morphological, and molecular techniques analyzed the challenge between the activation of hepatic LX2 stellate cells with noradrenaline and the possible reduction of this activation with tamsulosin and carvedilol treatments. In vivo, male Wistar rats were intoxicated with thioacetamide for 4 weeks to induce liver fibrosis, then treated orally with carvedilol and tamsulosin for 4 weeks. Hepatic function, histological, and molecular evaluation were made. In-situ perfusion was used to evaluate portal pressure. Norepinephrine (NE) induced increasing collagen-1 and α-SMA genes expression, while reducing PPAR-γ. Tamsulosin inhibited NE-induced proliferation, migration, and activation of HSCs, otherwise carvedilol showed partial effects. In vivo, tamsulosin treatment improved liver fibrosis, reduced collagen I levels, and normalized liver function. Additionally, in a thioacetamide-induced cirrhosis rat model, tamsulosin treatment prevented development of portal hypertension or arterial hypotension. Our results demonstrate that NE promotes hepatic stellate cell activation and fibrosis, while tamsulosin and carvedilol effectively reduce these effects in vitro and in vivo, without affecting the regenerative capacity of hepatocytes. In addition, the treatment also alleviates portal hypertension without causing systemic hypotension.