Protective effect of daidzein against acute ethanol-induced lipid peroxidation in rat jejunum.

Abstract

Ethanol causes extensive damage to the intestinal tract from the oropharynx to the rectum. The jejunum has also been shown to be particularly vulnerable to the deleterious effects of ethanol. We hypothesized that (I) the pathogenesis of acute alcohol-mediated injury in the small intestine involves generation of reactive oxygen species, and consequentially, enhanced lipid peroxidation; (II) the pathogenic changes due to alcohol can be ameliorated with daidzein pretreatment. To test these hypotheses male Wistar rats (n=24) were divided into four groups as follows (pretreatment followed by treatment): [A] carrier+saline (control); [B] daidzein+saline; [C] carrier+ethanol; [D] daidzein+ethanol. Daidzein (100 mg/kg) or carrier (Intralipid) pretreatment was twice administered as a single dose, whereas ethanol (75 mmol/kg) or saline (0.15 mol/l NaCl) treatment was administered once only. At 24 h after ethanol or saline was administered, rats were sacrificed. The analytes 7alpha-and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH), 7alpha-and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH), and 7-ketocholesterol (7-keto) in jejunum were analyzed by HPLC. The data showed that daidzein per se did not affect levels of cholesterol hydroperoxides nor oxysterols. However, there were significant increases in 7alpha- and 7beta-OOHs, 7alpha- and 7beta-OHs, and 7-keto after ethanol dosage compared to controls. Daidzein ameliorated these effects, i.e., values in the daidzein+ethanol group were similar to those in the carrier+saline (control) group. This is the first report showing that (1) cholesterol-derived markers of oxidative stress are increased in the rat jejunum in response to ethanol, indicative of metabolic damage; (2) daidzein pretreatment has protective effects against ethanol-induced injury.