Hepatic and biliary levels of glutathione and lipid peroxides following iron overload in the rat: effect of simultaneous ethanol administration.
The administration of 125 mg of iron/kg (iron-dextran-Imferon) to fed rats was followed by an increase in the non-hem iron content in plasma and liver over a period of 22 hr, reaching a peak value after 6 hr. Plasma and hepatic iron levels were not modified by ethanol ingestion (5 g/kg). Iron and ethanol treatments enhanced liver lipid peroxidation (malondialdehyde (MDA) formation) by 70 and 35%, respectively, at 6 hr. Since the hepatic MDA formation increased by 92% after the joint iron-ethanol treatment, an additive effect in lipid peroxidation was suggested to occur in this condition. Both iron and ethanol treatments increased biliary levels and release of MDA, in the absence of changes in bile flow. These parameters were further enhanced by the joint iron-ethanol exposure, in that hepatic MDA levels and biliary MDA release were significantly correlated (r = 0.86; p less than 0.05). Plasma MDA levels also increased after iron, ethanol, and iron-ethanol treatments, but they did not reflect the changes in MDA levels in liver. Iron exposure resulted in 26 to 33% decreases in hepatic GSH content at the 6-hr treatment, associated with the peak effect on lipid peroxidation. In this situation, glutathione disulfide (GSSG) levels in liver were not changed, but its biliary release increased by 76%. Hepatic reduced glutathione (GSH) levels were recovered by 18 hr and increased by 23% after 22 hr of iron ingestion. Acute ethanol intake diminished liver GSH content by 30% and enhanced that of GSSG by 73%, thus eliciting a net decrease of 20% in total GSH equivalents (GSH + 2GSSG). Biliary release of total GSH was reduced in this condition. The combined administration of iron and ethanol further influenced the decrease in hepatic GSH and the increase in GSSG levels elicited by the separate treatments, but no alterations in the biliary content and release of total GSH were observed in this situation. These data indicate that iron exposure accentuates the changes in lipid peroxidation and in the glutathione status of the liver cell induced by acute ethanol intoxication.
D000818:Animals; D001646:Bile / Q000032:analysis*; D000431:Ethanol / Q000633:toxicity*; D005978:Glutathione / Q000032:analysis*; D007501:Iron / Q000032:analysis / Q000633:toxicity*; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000032:analysis* / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D000431:Ethanol; D008315:Malondialdehyde; D007501:Iron; D005978:Glutathione