Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals

Abstract

Ethanol metabolism by cytochrome P4502E1 (CYP2E1) produces free radical intermediates, identified as hydroxyethyl radicals. We have observed that in vitro addition or in vivo pretreatment of rats with Silipide, a new 1:1 complex of silybin with phosphatidyl-choline, is able to decrease the spin trapping of hydroxyethyl radicals in microsomes from chronic alcohol-fed rats. This effect is not due to an interference with the metabolism of ethanol by CYP2E1, but is rather related to the capacity of the silybin molecule to scavenge hydroxyethyl radicals. However, such an effect is lost when pure silybin in amounts comparable to those present in Silipide is administered instead, due to the low bioavailability of uncomplexed flavonoid. Further experiments in vivo have shown that Silipide administration also decreases hydroxyethyl radical signals detectable in the bile of rats acutely treated with ethanol. The ability of Silipide to scavenge ethanol-derived radicals along with its antioxidant activity suggests that this drug might be potentially useful in counteracting free radical-mediated injuries involved in the development of liver damage caused by alcohol abuse.