Liver injury model induced in mice by a cellular immunologic mechanism--study for use in immunopharmacological...

Various drugs for clinical hepatitis were applied to a new model of liver injury induced in mice by delayed-type hypersensitivity to picryl chloride (PCI-DTH). The hepatoprotective agent, biphenyl dimethyl dicarboxylate showed a remarkable improvement against the elevation of serum transaminase levels as well as the histopathological changes when given during the induction phase but not during the effector phase of DTH reaction. Cyclophosphamide (Cy), an immunosuppressive agent, significantly inhibited the enzymatic elevation given in both induction and effector phases. However, Cy did not affect the sustaining of liver injury 4 weeks after the liver injury eliciting. Moreover, the consecutive administration of prednisolone (Pred), in both induction phase and sustaining process of liver injury, conversely caused a more severe liver damage. Such exacerbation by Pred might be resulted from its toxic action to hepatocytes. As an immunomodulatory and antiinflammatory agent, glycyrrhizin remarkably improved the sustaining process but not the acute phase of the liver injury. Krestin and malotilate also showed an improving effect on the sustaining development of liver injury. These findings that most of above drugs showed an improving action in their respective manner suggest that this model may be useful for the pharmacological evaluation of drugs especially immunomodulating agents for hepatitis.