A role for oxidative stress in suppressing serum immunoglobulin levels in lead-exposed Fisher 344 rats

Evidence implicating oxidative stress in toxicity during lead intoxication in vivo has opened new avenues for investigation of the mechanisms of lead- induced immunosuppression. The current study explores the possibility that lead-induced oxidative stress contributes to the immunosuppression observed during lead poisoning. Fisher 344 rats were exposed to 2,000 ppm lead acet ate in their drinking water for 5 weeks. One week following removal of lead from the drinking water, significant reductions in serum levels of IgA, Ig M, and IgG were detected. Significant increases in oxidative damage, based on malondialdehyde (MDA) content, were observed in peripheral blood mononuc lear cells (PMCs) collected during the same experiments. In addition, MDA c ontent increased in livers from lead-exposed rats. Following 5 weeks of lea d exposure, administration of either 5.5 mmol/kg N-acetylcysteine (NAC) or 1 mmol/kg meso-2,3-dimercaptosuccinic acid (DMSA) in the drinking water for 1 week significantly reversed the inhibitory effects of lead on serum immu noglobulin (Ig) levels. Also, all parameters indicative of oxidative stress returned to control levels. These results suggest that oxidative stress co ntributes to suppressed serum Ig levels during lead intoxication in vivo, a nd that intervention with either a thiol antioxidant (NAC) or a metal chela tor (DMSA) will alleviate this lead-induced suppression by correcting the p rooxidant/antioxidant imbalance caused by lead exposure.