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المستخلص Cyclophosphamide (CP) is a widely used antineoplastic drug, which causes toxicity of the normal cells due to its metabolites. The present work studied the induced cell damage in liver and brain cells of mice after chronic administration of CP (0.4mg/20 g mice) for 5, 10 or 15 consecutive days. Semi-quantification for the expression of genes encoding for the antioxidant enzymes {Glutathione peroxidase (GPX) and Superoxide dismutase (SOD)} were measured, using the reverse transcriptase polymerase chain reaction ( RT- PCR) technology. Results indicated that chronic cyclophosphamide administration resulted in a substantial variation in the expression of genes involved in the antioxidant defence mechanism in liver and brain cells of treated mice. In liver cells, SOD gene expression was slightly activated after CP treatment for five and ten days. After fifteen days of CP treatment SOD mRNA was slightly decreased, compared to the control. However, these changes were not statistically significant. In the mean time, GPX expression has been declined in 5 and 10 days groups to reach significant decreased levels after15 days of the treatment, compared to the control and compared to that of 5 days. In brain cells, there was a significant decrease in the levels of expression of SOD in the three treated groups, compared to the control. A statistically decreased GPX expression in the 5 days group, compared to the control was also recorded . However, there was a significant increase in the gene expression of GPX in 10 days and 15 days groups compared to the 5 days group. Results also revealed that linearly statistically significant increase in the SOD/GPX expression ratios in liver cells, possibly implying oxidative stress increase was induced by CP treatment. SOD/GPX expression ratios in the brain cells showed a linearly statistically significant decrease prolonging CP treatment for 15 days. These decreased ratios suggest a possible reduced oxidative stress in brain cells. The results obtained from the present study suggest that the liver was injured by chronic treatment with CP and confirm the development of an adaptive response in the brain cells by up regulating GPX gene expression. |