Abstract
The effects of a novel hepatoprotective compound, 8-(2-di-methylaminoethyl)-3-oxo-4-pheny1-1-thia-4,8-diazaspiro[4,5] decane dihydrochloride (Y-8845), on various kinds of experimental liver injury were investigated. CCl4 administered to rats (0.67 ml/kg i.p.) produced a marked increase in serum GOT and GPT activities, with a maximal response 24 hr after administration. Pretreatment with Y-8845 dose-dependently reduced these increases in enzyme activities and improved disorders in ICG excretion and liver weight. This protective action against CCl4 hepatotoxicity was confirmed by histopathologic evaluation: the reduction of CCl4-induced centrilobular necrosis was marked,and areas with a normal architectural pattern were more extensive. The hepatoprotective effects of Y-8845 were also found in other models of liver injury, ie., injury induced by thioacetamide, galactosamine, ct-naphtylisothiocyanate and endotoxin. Furthermore, anti-fibrotic action was observed in egg yolk-induced chronic hepatic fibrosis. These findings suggest that Y-8845 has potential as a hepatoprotective agent.
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