Department of Analytical Chemistry, Medical University of Białystok, Białystok, Poland.
Toxicol Mech Methods. 2003;13(4):301-8. doi: 10.1080/713857191.
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.
环磷酰胺是一种用于化疗的烷化剂化合物，在体内代谢为活性代谢物，形成活性氧。在抗氧化能力下降的情况下，活性氧可以修饰健康细胞和肿瘤细胞的成分。这导致器官功能障碍，包括肾脏。因此，在环磷酰胺治疗期间可以使用像氨磷汀这样的药物来保护健康细胞免受活性氧的损伤。本研究的目的是评估氨磷汀对接受环磷酰胺治疗的大鼠肾脏抗氧化系统的影响。腹腔内给予环磷酰胺会降低肾脏抗氧化酶的活性，如超氧化物歧化酶、谷胱甘肽过氧化物酶、谷胱甘肽还原酶和过氧化氢酶。然而，氨磷汀会导致这些酶的活性增加。与环磷酰胺联合使用氨磷汀部分预防了环磷酰胺注射后观察到的这些酶活性的变化。环磷酰胺还会导致非酶抗氧化剂如还原型谷胱甘肽、维生素 C 和维生素 E 以及总抗氧化状态的水平降低。与环磷酰胺联合使用氨磷汀可防止评估的非酶抗氧化参数浓度的变化，将其浓度增加到对照组的水平。环磷酰胺解毒过程中肾脏抗氧化能力的变化伴随着脂质过氧化的增强，表现为丙二醛和 4-羟壬烯醛浓度的增加。氨磷汀可抑制对照组和环磷酰胺处理大鼠肾脏的脂质过氧化。总之，我们的结果表明，氨磷汀可显著保护肾脏抗氧化参数免受环磷酰胺治疗引起的变化，从而防止氧化应激和磷脂过氧化损伤。因此，氨磷汀可预防肾脏损伤和功能障碍。
