الفهرس 
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Abstract
The present study aimed to detect sub chronic toxicity of lead acetate on adult male albino rats by assessing its impact on the serum biochemical parameters, and to demonstrate its effects on oxidative stress and antioxidant status as a physiological bioindicators of toxicity in liver and kidney, and gene expression of hepatic antioxidant enzymes using quantitative Real-Time PCR, as well as to emphasis its histopathological alterations in liver and kidneys of rat. Also, to evaluate possible protective and therapeutic effect of dietary supplementation of aqueous extract of ginger against Pb toxicity in adult male rats. Therefore Male albino rats (8 weeks old, weighing about 100-120 gm) were used in this experiment. Animal was feed standard ration and allowed access to water ad libitum. All rats were housed in metal box cages for 1 week prior to the experiment for acclimatization and to ensure normal growth and behavior. After the week of the acclimatization, rats were randomly divided into six groups, group one served as control without any treatment, group two supplemented with ginger (350 mg/ kg B.W), group three exposed to lead acetate (150 mg/ Kg), group four exposed to Pb+ GE, group five exposed to Pb for 6 weeks and then left for spontaneous recover for another 2 weeks and group six exposed to Pb for 6 week then treated with ginger for another 2 weeks. The period of the experiment was 8 weeks. Randomly, 3 rats were collected from each group from which blood and tissue samples were collected at 2nd , 4th , 6th and 8th week of exposure, to determine serum biochemical parameters, LPO levels and antioxidants in tissue homogenate of liver and Kidney, histopathological alterations in liver and kidneys, and level of hepatic antioxidant enzymes mRNA gene expression Our results revealed that Pb concentration was increased in liver and kidney of Pb-intoxicated groups and ginger supplementation had no observable effect on the Pb concentration there was an increment in hepatorenal GSH and GST levels with decreasing in activity of hepatic GPx and catalase enzymes, while there was increasing in renal GPx activity with no effect on renal catalase level. Also, there was no effect observed in hepatic SOD activity, while there was decreasing in renal SOD activity in lead exposed rats There was increasing in serum GOT, urea and creatinine levels in rats treated with lead There was an increment in hepatorenal level of LPO There was improvement in antioxidant enzymes activity, LPO and serum GOT, urea and creatinine levels in rats co-treated with Pb plus ginger LPO and antioxidant enzymes activity return to normal values in with drawl rats with or without treatment with improvement in serum GOT, urea and creatinine levels There was down regulation in hepatic mRNA expression of GST,SOD, Catalase and GPX enzymes in Pb exposed rats Ginger had inhibitory effect on gene expression of GST,SOD and catalase enzymes, while it up-regulate mRNA expression of GPx enzyme mRNA expression of GST, GPx and catalase genes was up-regulated in rat treated with Pb plus ginger with down regulation of SOD gene expression GST, GPx and catalase genes expression were up-regulated in with drawal rat without treatment There were differences observed in gene expression and enzyme activity among rats of some groups Microscopic examination of liver and kidney tissue in rats which exposed to Pb showed Pathological lesions which increased in its severity with increasing time of exposure Histopathological examination to liver of Pb treated rats showed hydropic degeneration where the cells are swollen, cytoplasm is replaced by clear fluids, and the nucleus not affected either in shape or location, fatty degeneration which characterized by large empty vacuoles of sharp borders, which replaced almost the cytoplasm, infiltration of inflammatory cells in the area of portal area, beside edematous separation of blood vesicle from adjacent cells were evident and necrotic hepatocytes with inflammatory cells infiltrations Microscopic examination to kidney of Pb treated rats showed vacuolar and hydropic degeneration of the epithelium lining of renal tubules. in adition to congestion of intertubular blood capillaries, congestion of capillaries tuft and hyaline cast which characterized by homogeneous structurless eosinophilic material take shape of renal tubules. Moreover, hyalinized wall of glomureuli was noticed and interstitial nephritis which characterized by inflammatory cells infiltration in the interstitial tissue around renal tubules and glomureuli Hepatic and renal lesions decreased in its severity in Pb treated rats which co-treated with ginger. But liver and kidney tissues did show any improvement in the pathological lesions which induced by Pb after with drawl of it with or without ginger treatment And from these results we can concluded that- Sub-chronic exposure to Pb at given concentration induced oxidative stress and hepatorenal toxicity in rats as evidenced by biochemical and histopathological alterations Sub-chronic exposure to Pb induced down-regulation in gene expression of the antioxidant enzymes (GST, GPx, SOD and catalase) in rats 3- Ginger has protective and therapeutic effect against sub-chronic toxicity of lead acetate in male albino rats. However, Protective effect of ginger is more pronounced than its therapeutic effect 4-Prolonged administration of external antioxidants (as ginger) should be avoided to prevent its harmful effects on endogenous antioxidants.