tranilast and Liver-Diseases--Parasitic

The ability of tranilast, a mast cell stabilizer and anti-transforming growth factor(β) (TGF(β)) to improve impaired hepatic functions in Schistosoma mansoni (S. mansoni)-infected mice, was investigated, providing the first evidence on the ability of tranilast to improve hepatic impairment due to schistosomal infection. Tranilast had significant beneficial effects against progression of hepatic fibrosis in S. mansoni-infected mice treated with praziquantel and those untreated. Different aspects of drug activity were investigated. Its effect on serum liver functions was evaluated by estimating: alanine aminotransferase, aspartate aminotransferase, total bilirubin, alkaline phosphatase and albumin. Its effect on the extent of liver fibrosis, through estimation of hepatic hydroxyproline and hepatic collagen content in liver hydrolysates, was also evaluated. Also, the expression of profibrogenic mediators, such as serum TGF(β1), was estimated. Finally, the effect on S. mansoni infection itself was studied, via histopathological examination of liver specimens stained with both hematoxylin-eosin and Masson's trichome stains. Tranilast ameliorated the harmful effects of S. mansoni infection on the liver. Such action was manifested in its significant ability to improve impaired hepatic functions, reduce histopathological changes, lower hepatic collagen content and finally reduce serum TGF(β1) levels. The beneficial effect of tranilast may be in part due to its ability to reduce the production of profibrogenic mediators in the infected animals by improving the host immune response or by interfering with critical steps in the fibrogenic cascade.

Topics: Animals; Anthelmintics; Disease Models, Animal; Drug Therapy, Combination; Liver Cirrhosis; Liver Diseases, Parasitic; Liver Function Tests; Male; Mice; ortho-Aminobenzoates; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Transforming Growth Factor beta1; Treatment Outcome