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

Abstract

Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against carbon tetrachloride (CCl₄) 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 Ca²⁺-stimulated permeability transition (PT) was investigated in mouse livers under normal and CCl₄-intoxicated conditions. CCl₄ hepatotoxicity caused an increase in the sensitivity of mitochondria to Ca²⁺-stimulated PT in vitro. The enhanced sensitivity to mitochondrial PT was associated with increases in mitochondrial Ca²⁺ content as well as the extent of reactive oxidant species (ROS) production and cytochrome c release. The hepatoprotection afforded by Sch B pretreatment against CCl₄ toxicity was paralleled by the decrease in the sensitivity of hepatic mitochondria to Ca²⁺-stimulated PT as well as the attenuations of mitochondrial Ca²⁺ loading, ROS production and cytochrome c release under CCl₄-intoxicated condition. In conclusion, the results suggest that the hepatoprotection afforded by Sch B pretreatment against CCl₄ toxicity may be related to the increase in the resistance of hepatic mitochondria to Ca²⁺-stimulated PT.