ANTIOXIDANT EFFECTS OF N-ACETYLCYSTEINE AND SUCCIMER IN RED-BLOOD-CELLS FROM LEAD-EXPOSED RATS

This study examined whether lead-induced alterations in selected param eters that are indicative of oxidative stress accompany the toxic effe cts of lead in red blood cells (RBCs) in vivo. It also explored the po ssibility that treatment with N-acetylcysteine (NAC) or succimer (meso -2,3-dimercaptosuccinic acid) was capable of reversing parameters indi cative of lead-induced oxidative stress. Fisher 344 rats were given 20 00 ppm lead acetate in their drinking water for 5 weeks. The lead was then removed and the animals were given NAC (800 mg/kg/day) or succime r (90 mg/kg/day) in their drinking water for 1 week, after which the R BCs were harvested. Animals not given lead and those given lead, but n ot NAC or succimer, served as negative and positive controls, respecti vely. At the end of the experiment, blood-lead levels were 35 +/- 4 mu g/dl in lead-treated animals, which were reduced to 2.5 +/- 1 mu g/dl by treatment with succimer and to 25 +/- 3 mu g/dl by treatment with NAG. Lead-exposed animals demonstrated signs of anemia as evidenced by anisocytosis, poikilocytosis, and alterations in hemoglobin, hematocr it, and mean corpuscular volume. Lipid peroxidation, as evidenced by i ncreased malondialdehyde (MDA) content; as well as decreases in reduce d glutathione (GSH) and increases in catalase and glucose 6-phosphate dehydrogenase (G6PD) activity were noted in RBCs from lead-treated rat s, suggesting that the lead induced oxidative stress. In addition, a s ignificant reduction in blood delta-aminolevulinic acid dehydratase (A LAD) activity suggested that accumulation and autooxidation of delta-a minolevulinic acid might contribute to lead-induced oxidative stress. Treatment with either NAC or succimer reversed lead-induced alteration s in MDA and GSH content, but only succimer appeared to partially rest ore ALAD activity. These results provide in vivo evidence supporting t he hypothesis that lead induces oxidative stress in RBCs, which is rev ersible by treatment with a thiol antioxidant (NAC), as well as a chel ating agent (succimer). (C) 1998 Elsevier Science Ireland Ltd. All rig hts reserved.