الفهرس 
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Abstract
Lead is a hazardous substance in humans and animals. It is a common environmental and industrial pollutant that has been detected in all phases of environment (air, water and soil) and biological system. It has been found to produce wide range of toxic biochemical effects in man and experimental animals. Despite mandated reduction in environmental lead, such exposure still poses a public health hazard for children, with devastating effects on CNS development This study was performed with the aim of: to study the protective effect of ascorbic acid, ga stocopherol, Nacetylcysteine and Lmethionine against oxidative stress produced by chronic lead exposure in male Albino rats. This study was planed as follow: This study included 160 male Albino rats. Their weights ranged from 250300 gm. Rats were divided into control (negative control), group I (positive control) and 7 test groups. Each test group is divided into two subgroups (a) and (b). Subgroups (a) are the prophylactic groups (prior to lead dose) and subgroups (b) are the treatment groups (after lead dose). Antioxidants (ascorbic acid, gastocopherol, Nacetylcysteine and Lmethionine) are given to test groups either single or in combination. For each animal, blood samples were taken by cut throat (4.55 ml) and collected into three test tubes. The first tube contained whole blood on heparin, which is used for determination of RBCs content of: glutathione peroxidase, superoxide dismutase, and lead level. The second tube contained whole blood without preservative was centrifuged and the collected serum was analysed for the levels of Thiobarbituric Acid Reactive Substance (TBARS), total thiol concentration, and total protein concentration.The third tube contained whole blood on EDTA, which is used for complete blood picture assay. The weights of rats were determined weekly. After animals were sacrificed, liver, kidney and brain were fixed in 10% neutral formalin stained with Haematoxyllin and Eosin (H&E) for microscopic examination. Results revealed: Lead treatment (1 mg/kg b.w. lead acetate intraperitoneally for a period of 9 weeks) disrupts the oxidant/antioxidant balance and induces oxidative stress such as increase in TBARS concentration, decrease in total protein concentration, decrease in total thiol concentration, decrease in glutathione peroxidase concentration, decrease in SOD concentration, and increase in blood lead leve. Also, the effects of lead on the haematological system are decrease in haemoglobin concentration, red blood cells count, platelets count as well as HCT percent and there was a significant increase in WBCs count. There are histopathological influences of lead toxicity on liver, kidney and brain. There is significant negative correlation of blood lead level and the biochemical parameters (total protein, total thiol, GPx, SOD concentration) and CBC (haemoglobin, RBCs, platelets, HCT). Also, there is significant positive correlation of blood lead level and TBARS and WBCs. Multiple stepwise regression models were done to determine significant predictors that affect level of lead. TBARS was the most significant predictor affect lead then, HCT was the second predictor and total thiol was the third predictor then followed by glutathione peroxidase (GPx) and superoxide dismutase (SOD). The antioxidants (ascorbic acid, ga stocopherol, Nacetylcysteine and Lmethionine) either before or after lead exposure (single or in combination) have a protective role in reducing the lipid peroxidation and leadinduced oxidative stress. The use of antioxidants before and after lead exposure significantly improved the haematological changes. The concomitant use of antioxidants (before and after lead exposure) resulted in an improvement of the histopathological changes in the liver, kidney and brain. The results of prophylactic groups (subgroups a) considered better than the treatment groups (subgroups b) and this may be due to the short periods that the treated test groups were exposed to antioxidants (7 days). The use of antioxidants (ascorbic acid, ga stocopherol, Nacetylcysteine and Lmethionine) combined together before lead exposure (for 9 weeks) showed the best response (group VIIIa) than other groups. Regarding, the body weight of the animals, there is a weight gain in all prophylactic groups (IIa, IIIa, IVa, Va, VIa, VIIa, and VIIIa) with the maximum percentage (66%) in group VIIIa while, the other groups received antioxidants after lead treatment (IIb, IIIb, IVb, Vb, VIb, VIIb, and VIIIb) showed a significant weight loss till the 8th week and these groups showed increase in the weight during the 9th week (during the treatment with the antioxidants). This study has concluded that: Supplementation with antioxidants (ascorbic acid, gastocopherol, Nacetylcysteine and Lmethionine) in adjusted dose is a potential therapy in the lead intoxication and The most protective treatment is the use of combined antioxidants (ascorbic acid, ga stocopherol, NAC and Lmethionine) before lead exposure.