Abstract
Our previous study has already confirmed a promising anti-fibrotic activity especially for nilotinib; when given at a daily dose of 10mg/kg during the last 4weeks of thioacetamide (TAA)-induced liver fibrosis for 12weeks in rats. Therefore, this study was carried out to compare the prophylactic potential of low dose of nilotinib to that of its predecessor, imatinib, and a clinically relevant dose of the standard hepatoprotective treatment, silymarin, in TAA-intoxication. Male Wistar rats received intraperitoneal injections of TAA (150mg/kg, twice weekly) for 8weeks, as well as oral treatments with imatinib (5mg/kg/day), nilotinib (5mg/kg/day) and silymarin (50mg/kg/day) from the first day of TAA-intoxication. At the end of the study, chronic hepatic injury was evaluated by analysis of liver function tests in serum. Hepatic oxidative stress was assessed by measuring malondialdehyde, 4-hydroxynonenal, total nitrate/nitrite and reduced glutathione contents, as well as myeloperoxidase and superoxide dismutase activities. Hepatic fibrosis was evaluated by histopathology and collagen content. Our results suggest that the prophylactic potential of nilotinib (5mg/kg/day), imatinib (5mg/kg/day) and silymarin (50mg/kg/day) in TAA-intoxication for 8weeks is lower than the late treatments of nilotinib (10mg/kg/day), imatinib (10mg/kg/day) and silymarin (100mg/kg/day) during the last 4weeks of TAA-intoxication for 12weeks in rats. Taken together, this study suggests that nilotinib may have higher anti-fibrotic activity when administered at a significant stage of fibrosis as a result of impairment of its metabolism in the fibrotic livers.
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