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.
Highlights
Kidney and liver are vital organs that participate actively in metabolic homeostasis, during which a number of reactive oxygen species (ROS) generating reactions are involved
CCl4-induced liver damaged was associated with a significant impairment in the mitochondrial glutathione redox status, as assessed by the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, in rat livers (Figure 2a)
While BSS pretreatment produced no detectable effect on mitochondrial glutathione redox status in non-CCl4-intoxicated rat livers (Figure 2a), BSS, at daily doses of 35 μg/kg, partially reversed the CCl4-induced impairment in mitochondrial glutathione redox status by 61%, when compared with the untreated CCl4 control (Figure 2a)
Summary
Kidney and liver are vital organs that participate actively in metabolic homeostasis, during which a number of reactive oxygen species (ROS) generating reactions are involved. The metabolic role of these organs makes them more vulnerable to oxidant injury [1,2,3,4] In this connection, experimental findings showed that events such as ethanol consumption [5], drug exposure [6], acute exercise and aging [7,8] were found to be associated with a shift of cellular redox environment to a more oxidized state in the kidney and liver, indicative of oxidative stress, with resultant impairment in cellular and mitochondrial functions [9]. A phytosterol, β-sitosterol (BSS, Figure S1, Table S1), was identified as an active component of Cistanches Herba in enhancing mitochondrial respiration and thereby improving glutathione redox status via an induction of mitochondrial ROS production in H9c2 cardiomyocytes. Mitochondrial glutathione redox status and mitochondrial functional ability in rat kidney and liver tissues were examined
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