β-Sitosterol Protects against Carbon Tetrachloride Hepatotoxicity but not Gentamicin Nephrotoxicity in Rats via the Induction of Mitochondrial Glutathione Redox Cycling

Molecules

Hoi-Shan Wong²  Ji-Hang Chen²  Pou-Kuan Leong²  Hoi-Yan Leung²  Wing-Man Chan²  Kam-Ming Ko¹ 

[1] Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, China;

关键词: Cistanches Herba;    β-sitosterol;    carbon tetrachloride hepatotoxicity;    gentamicin nephrotoxicity;    glutathione redox cycling;    mitochondria;   

DOI  :  10.3390/molecules191117649

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.