Mostafavi-Pour Z et al. (2008) Protective effects of a combination of quercetin and vitamin E against cyclosporine A-induced oxidative stress and hepatotoxicity in rats. Hepatol Res 38: 385–392
Generation of reactive oxygen species and lipid peroxidation have been proposed as the mechanisms that underlie ciclosporin hepatotoxicity. Mostafavi-Pour et al. investigated whether the antioxidants vitamin E and quercetin could protect against ciclosporin-induced liver damage in rats.
Male Sprague–Dawley rats were given ciclosporin alone, or ciclosporin plus either quercetin, vitamin E, or both. Olive oil or ethanol plus olive oil were used as a vehicle. Compared with controls, ciclosporin-fed animals had increased serum levels of alanine and aspartate aminotransferases and alkaline phosphatase, and decreased albumin and total protein levels. Administration of either vitamin E or quercetin reduced the toxic effects of ciclosporin, and in combination these agents maintained liver-function markers at control values. Ciclosporin increased the levels of liver thiobarbituric-acid-reactive substances (end-products of lipid peroxidation) and decreased levels of catalase and glutathione peroxidase, both of which defend against oxidative stress. Again, administration of either antioxidant reduced these toxic effects, and administration of both vitamin E and quercetin completely abrogated these effects of ciclosporin. Inflammation and extensive necrosis was seen in liver sections from rats fed ciclosporin; this damage was not seen in control rats or in those treated with ciclosporin plus vitamin E or quercetin, or both.
The authors conclude that vitamin E and quercetin protect against the oxidative liver damage caused by ciclosporin; potentially, these antioxidants could have a clinical benefit in transplant recipients.
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Antioxidants protect against the hepatotoxic effects of ciclosporin in rats. Nat Rev Gastroenterol Hepatol 5, 355 (2008). https://doi.org/10.1038/ncpgasthep1174