Schisandrin B decreases the sensitivity of mitochondria to calcium ion-induced permeability transition and protects against carbon tetrachloride toxicity in mouse livers.
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.
Chiu
Po Yee
PY
Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong SAR, China.
Leung
Hoi Yan
HY
Siu
Ada Hoi Ling
AH
Poon
Michel Kong Tat
MK
Ko
Kam Ming
KM
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects*; D034242:Cyclooctanes / Q000737:chemistry / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D007477:Ions / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism*; D015394:Molecular Structure; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D034242:Cyclooctanes; D007477:Ions; D017705:Lignans; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C015499:schizandrin B; D045304:Cytochromes c; D002251:Carbon Tetrachloride; D002118:Calcium