Effect of alpha-tocopherol on tissue transglutaminase and reversibility of thioacetamide-induced liver fibrosis in rats [Alfa-tokoferol'ün doku transglutaminazlar üzerine etkisi ve s anda tiyoasetamid uyar ml gerid nü ümlü karaci er fibrozu]

Both experimental and clinical studies have suggested the association between the deposition and stabilization of the extracellular matrix (ECM) proteins, and the development of liver fibrosis. Tissue transglutaminase (tTG) is known to stabilize the ECM proteins by its crosslinking activity that may play a key role in the development of liver fibrosis. This work was designated to evaluate the curative and/or the protective effect of α-tocopherol in relation to the activity of tTG in liver fibrosis. To establish this goal the effects of α-tocopherol on oxidative stress (measured as malondialdehyde, MDA), liver fibrosis (evaluated histologically and as hepatic collagen), and the activity of tTG were investigated in liver fibrosis generated in rats by intraperitoneal injection (i.p.i.) of thioacetamide (TAA). The data showed that α-tocopherol, significantly decreased the level of hepatic malondialdehyde when it was administrated after or before TAA treatment (P <0.001 and P <0.001, respectively). Similar changes in the level of hepatic collagen were observed, where the hepatic collagen, reduced when α-tocopherol was administrated after and partially before TAA treatment (P <0.001 and P >0.05, respectively). Although, TAA increased the tTG activity, α-tocopherol, variably lowered the enzyme activity when it was taken after, during or before TAA treatment. The histopathologic score of fibrosis was lower in rats treated with TAA then α-tocopherol compared with TAA only. The data suggest that TAA-induced liver fibrosis was reversed by α-tocopherol after the fibrotic inducer was eliminated. Also, α-tocopherol largely protects against the subsequent oxidative stress and liver fibrosis and slightly decrease the tTG activity after, during or before TAA treatment. The data indicate that, α-tocopherol functions as a potent fibrosuppressant and antioxidant, and may be a therapeutic choice.