الفهرس 
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Abstract
Lead has been the cause of serious risks to man specially in developing
countries. Lead acetate disturbed biochemical and hematological indices and induced hepatoxicity, neurotoxicity and nephrotoxicity through profound elevation of reactive oxygen species (ROS) production and oxidative stress, leading to increased lipid peroxidation level and depletion of intracellular reduced glutathione
(GSH) level in kidney and liver. The present study aimed to assess effect of lead poisoning on the telomerase gene expression, which is related to DNA synthesis, with screening the reversibility of some harmful biophysical and biochemical effects generated by lead poisoning after application of both chemical and natural lead chelators (dimercaptosuccinic acid and Angelica archangelica). Animal study design was conducted on ninety male Sprague-Dawley rats. Rats were divided into six groups, each contains 15 rats: Group I: Negative control group which represents rats did not receive lead through drinking water. Group II: positive control group, which represents rats received lead acetate (1000 ppm) through drinking water for 21 day.
Group III: which represents rats received lead acetate in water for 21 days and then received dimercaptosuccinic acid (DMSA) (50 mg/kg body wt.) orally using mouth injector three times per week for another 21 days with continuous exposure to lead acetate in water. Group IV: which represents rats received lead acetate in water for 21 days and then received (DMSA) (50 mg/kg body wt.) orally using mouth injector
three times per week for another 21 days without continuous exposure to lead.
GroupV: which represents rats received lead acetate in drinking water for 21 days
and then received extract of Angelica archangelica roots (75 mg/kg body wt.) orally
using mouth injector three times per week for another 21 days with continuous exposure to lead acetate in water. Group VI: represents rats received lead acetat in drinking water for 21 days and then receive extract of Angelica archangelica roots (75 mg/kg body wt.) orally using mouth injector three times per week for another 21 days without continuous exposure to lead acetate in water. Lead toxicity increased
blood and tissues lead concentration and free radicals formation followed by oxidative stress. These results lead to increase in the activities of antioxidant enzyme (to overcome the hazardous effects of lead poisoning) as well as in lipid peroxidation and decrease in the concentration of sulfhydryl groups. AST and ALT activities, total bilirubin, urea, creatinin and uric acid concentration were increased
while albumin and total proteins levels were decrease due to the toxic effect of lead.
On the other hand, this oxidative stress lead to shift in the ratio of apoptotic related proteins (p53 and Bcl2) toward apoptosis, which is confirmed by histopathological
examination of liver tissues. The effect of lead toxicity was revealed by reduced mRNA gene expression of telomerase enzyme. This result moves the cells toward senescence. Treatment with A. archangelica root extract and DMSA significantly decreased lead levels in rat blood and tissue samples, provided protection against lead-induced cellular liver damage, reversed almost all the damage to classic liver architecture and enhanced the mRNA gene expression of telomerase enzyme to prevent cells senescence. Hemoglobin intrinsic viscosity, auto-oxidation rate and electrical conductivity were affected by lead poisoning. In conclusion, this study assesses the effects of lead poisoning on the telomerase gene expression which III appears on decreasing mRNA gene expression of telomerase enzyme. This result
moves the cells toward senescence. Treatment with chelators significantly decreased lead levels in rats’ blood and tissue samples and enhanced the mRNA gene expression of telomerase enzyme. The effect of A. archangelica on lead toxicity treatment was more pronounced than DMSA.