Schisandrin B Decreases the Sensitivity of Mitochondria to Calcium Ion-Induced Permeability Transition and Protects against Carbon Tetrachloride Toxicity in Mouse Livers(Pharmacology)

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Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against carbon tetrachloride (CCl_4) hepatotoxicity in mice. In order to elucidate the molecular mechanism underlying the hepatoprotection afforded by Sch B, the effect of Sch B treatment on the sensitivity of mitochondria to Ca^<2+>-stimulated permeability transition (PT) was investigated in mouse livers under normal and CCl_4-intoxicated conditions. CCl_4 hepatotoxicity caused an increase in the sensitivity of mitochondria to Ca^<2+>-stimulated PT in vitro. The enhanced sensitivity to mitochondrial PT was associated with increases in mitochondrial Ca^<2+> content as well as the extent of reactive oxidant species (ROS) production and cytochrome c release. The hepatoprotection afforded by Sch B pretreatment against CCl_4 toxicity was paralleled by the decrease in the sensitivity of hepatic mitochondria to Ca^<2+>-stimulated PT as well as the attenuations of mitochondrial Ca^<2+> loading, ROS production and cytochrome c release under CCl_4-intoxicated condition. In conclusion, the results suggest that the hepatoprotection afforded by Sch B pretreatment against CCl_4 toxicity may be related to the increase in the resistance of hepatic mitochondria to Ca^<2+>-stimulated PT.
公益社団法人日本薬学会の論文
2007-06-01