Protection Against Cyclophosphamide-Induced Renal Oxidative Stress by Amifostine: The Role of Antioxidative Mechanisms

Cyclophosphamide, an alkylating compound used in chemotheraphy, is metabolized into active metabolites that form reactive oxygen species. Reactive oxygen species can modify the components of both healthy and neoplastic cells in circumstances of decreased antioxidative abilities. That leads to the dysfunction of organs, including the kidneys. Therefore, drugs like amifostine, which protect healthy cells against reactive oxygen species, may be applied during cyclophosphamide therapy. The aim of this study was to evaluate the influence of amifostine on the antioxidative system of the kidneys of rats that were exposed to cyclophosphamide. Intraperitoneal administration of cyclophosphamide was found to decrease the activity of the kidney's antioxidative enzymes, such as superoxide dismutase, glutathione peroxidase, gluthatione reductase, and catalase. Amifostine, however, caused an increase in the activity of these enzymes. The administration of amifostine with cyclophosphamide partially prevented changes in the activities of the examined enzymes observed after cyclophosphamide injection. Cyclophosphamide also evoked a decrease in the levels of nonenzymatic antioxidants, such as reduced gluthatione, vitamin C, and vitamin E as well as the total antioxidant status. The administration of amifostine together with cyclophosphamide prevented changes in the concentration of evaluated nonenzymatic antioxidative parameters, increasing values of their concentration to the values in the control group. Changes in the kidneys' antioxidative abilities during detoxification from cyclophosphamide were accompanied by intensified lipid peroxidation, which was manifested by an increase in the concentration of malondialdehyde and 4-hydroxynonenal. Amifostine caused the inhibition of lipid peroxidation in the kidneys of control and cyclophosphamide-treated rats. In conclusion, our results suggest that amifostine significantly protects kidney antioxidant parameters from changes caused by cyclophosphamide treatment and, in consequence, prevents oxidative stress and phospholipid peroxidative damage. Thus, amifostine prevents renal injury and dysfunction.