title: β-sitosterol protects against carbon tetrachloride hepatotoxicity but not gentamicin nephrotoxicity in rats via the induction of mitochondrial glutathione redox cycling.
abstract: Previous findings have demonstrated that β-sitosterol (BSS), an active component of Cistanches Herba, protected against oxidant injury in H9c2 cardiomyocytes and in rat hearts by enhancing mitochondrial glutathione redox cycling, possibly through the intermediacy of mitochondrial reactive oxygen species production. We therefore hypothesized that BSS pretreatment can also confer tissue protection against oxidant injury in other vital organs such as liver and kidney of rats. In this study, the effects of BSS pretreatment on rat models of carbon tetrachloride (CCl4) hepatotoxicity and gentamicin nephrotoxicity were investigated. The findings showed that BSS pretreatment protected against CCl4-induced hepatotoxicity, but not gentamicin nephrotoxicity in rats. The hepatoprotection afforded by BSS was associated with the improvement in mitochondrial glutathione redox status, presumably through the glutathione reductase-mediated enhancement in mitochondrial glutathione redox cycling. The hepatoprotection afforded by BSS was also accompanied by the improved mitochondrial functional ability in rat livers. The inability of BSS to protect against gentamicin nephrotoxicity was likely due to the relatively low bioavailability of BSS in rat kidneys. BSS may serve as potential mitohormetic agent for the prevention of oxidative stress-induced injury in livers.
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. bchelenwong@ust.hk.
authors.forename: Hoi-Shan
authors.initials: HS
authors.lastname: Wong
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. cjh@ust.hk.
authors.forename: Ji-Hang
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. eriol@ust.hk.
authors.forename: Pou-Kuan
authors.initials: PK
authors.lastname: Leong
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. hoiyan@ust.hk.
authors.forename: Hoi-Yan
authors.initials: HY
authors.lastname: Leung
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. wingman@ust.hk.
authors.forename: Wing-Man
authors.initials: WM
authors.lastname: Chan
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China. bcrko@ust.hk.
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Ko
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001682:Biological Availability; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005839:Gentamicins / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012855:Sitosterols / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005839:Gentamicins; D016877:Oxidants; D017382:Reactive Oxygen Species; D012855:Sitosterols; C025473:gamma-sitosterol; D002251:Carbon Tetrachloride; D005980:Glutathione Reductase; D005978:Glutathione