Biomarkers of oxidative stress study: Are plasma antioxidants markers of CC1(4) poisoning?

Antioxidants in the blood plasma of rats were measured as part of a compreh ensive, multilaboratory validation study searching for noninvasive biomarke rs of oxidative stress. For this initial study an animal model of CCl4 pois oning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl4 on plasma levels of alpha-toco pherol, coenzyme Q (CoQ), ascorbic acid, glutathione (GSH and GSSG), uric a cid, and total antioxidant capacity were investigated to determine whether the oxidative effects of CCl4 would result in losses of antioxidants from p lasma. Concentrations of alpha-tocapherol and CoQ were decreased in CCl4-tr eated rats. Because of concomitant decreases in cholesterol and triglycerid es, it was impossible to dissociate oxidation of alpha-tocopherol and the l oss of CoQ from generalized lipid changes, due to liver damage. Ascorbic ac id levels were higher with treatment at the earliest time point; the ratio of GSH to GSSG generally declined, and uric acid remained unchanged. Total antioxidant capacity showed no significant change except for 16 h after the high dose, when it was increased. These results suggest that plasma change s caused by liver malfunction and rupture of liver cells together with a de crease in plasma lipids do not permit an unambiguous interpretation of the results and impede detection of any potential changes in the antioxidant st atus of the plasma. (C) 2000 Elsevier Science Inc.