Unlabelled: BP 2-94 is a prodrug of the H3-receptor agonist (R)-alpha-methylhistamine [(R)-alpha-MeHA]. BP 2-94 displayed anti-inflammatory, antinociceptive and ulcero-protective properties in experimental animals.
Aim: The aim of the present study was to investigate the effect of BP 2-94 in a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats.
Materials And Methods: In order to investigate the effect of BP 2-94 it was applied to rats either alone (20, 40 and 60 micromol kg(-1), 4 days) or as a pretreatment (20, 40 and 60 micromol kg(-1), 4 days) before the application of CCl4 (0,2 ml kg(-1), 2 days).
Results: BP 2-94 in the tested doses did not cause significant changes in the plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities and the liver microscopic appearance was normal. Hepatocyte damage, as evident by local areas of liver necrosis and elevated levels of plasma AST and ALT, occurred in rats following acute exposure to CCl4 (0,2 ml kg(-1), 2 days). BP 2-94 applied as a pretreatment dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities in response to CCl4.
Conclusions: BP 2-94 had a hepatoprotective effect in a model of CCl4-induced toxicity in rats. This effect might be due the H3-agonistic activity of its active metabolite (R)-alpha-MeHA.
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