Experimental study on cimetidine in treatment of nonalcoholic steatohepatitis in rats
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AIM: To investigate the efficacy and mechanism of cimetidine in the treatment of rat nonalcoholic steatohepatitis (NASH). METHODS: Thirty male Sprague Dawley rats were randomly and averagely divided into group A, B and C. High-fat diet was given to the rats in group A and B to induce NASH model, and those in group C served as normal controls. Moreover, the rats in group B were intragastrically treated with cimetidine (200 mg/d) for 12 wk. The levels of cytochrome P450 (CYP450), CYP2E1 and the damages of liver tissues, as well as the level changes of alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, insulin, and hyaluronic acid (HA) were measured. The pathological changes of liver tissues were observed under light microscope. RESULTS: After modeling, the serum levels of ALT, AST, blood glucose, insulin, and HA, and the tissue contents of CYP450 and CYP2E1 were elevated. However, after cimetidine treatment, the levels of ALT (t = 5.16, P < 0.05), AST (t = 5.45, P < 0.05), and HA (T = 55, P < 0.05), the contents of CYP450 (t = 3.91, P < 0.05) and CYP2E1 (t = 1.95, P < 0.05), and the wet weight of liver (t = 9.24, P < 0.05), as well as the histological activity index (6.40 ± 5.85 vs 7.80 ± 4.60, t = 2.59, P < 0.05) were decreased significantly. The serum levels of blood glucose and insulin were not significantly different between group A and B (P > 0.05). CONCLUSION: Cimetidine can lessen the damages of hepatocytes through inhibiting the expression of CYP450 and CYP2E1.
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World Chinese Journal of Digestology