Lead intoxication: antioxidant defenses and oxidative damage in rat brain

Oxidative damage associated with the presence of lead (Pb) in the brain has been proposed as one possible mechanism involved in Pb toxicity. To invest igate this hypothesis, we examined the long-term effects of Pb2+ on paramet ers of oxidative stress in the brain from rats chronically exposed to the m etal (1 g Pb acetate/l drinking water). After 8 weeks of treatment, Pb2+-in toxicated rats (blood Pb concentration > 100 mu g/dl) showed lower body wei ght, and lower hematocrit and 5-aminolevulinic acid dehydratase activity as compared to controls. The content of brain 2-thiobarbituric acid-reactive substances (TBARS), an indicator of lipid oxidation, was significantly (P < 0.05) higher in the Pb2+-intoxicated animals than in controls. Higher acti vities of the antioxidant enzymes glutathione reductase and glutathione per oxidase, and a lower (44%) level of ubiquinol 10 were found in the brain of the Pb2+-treated rats, compared to controls. A negative correlation betwee n brain ubiquinol 9 (r(2) = 0.79), 10 (r(2) = 0.84) and blood Pb concentrat ion was observed. Brain alpha-tocopherol levels, superoxide dismutase activ ity and parameters of oxidative damage to proteins were similar between con trol and Pb2+-treated rats. The present results indicate that chronic Pb2intoxication induces an oxidative stress situation in rat brain. (C) 1999 E lsevier Science Ireland Ltd. All rights reserved.