Suzuki Y, Sudo J
Department of Toxicology and Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Jpn J Pharmacol. 1987 Oct;45(2):271-9. doi: 10.1254/jjp.45.271.
In order to elucidate toxic and protective mechanisms responsible for allopurinol-induced nephrotoxicity in rats, we investigated changes in plasma creatinine concentration, renal lipid peroxidation, and renal activities of xanthine oxidase, superoxide dismutase and catalase, as enzymatic factors in producing and scavenging oxygen radicals. The rats received subcutaneous injections of allopurinol in a dose of 100 mg/kg body weight, once a day for 3 days. In comparison to the control rats, the following changes were observed in the allopurinol-administered rats: an increase in plasma creatinine concentration, increases in renal contents of malonaldehyde, hypoxanthine and xanthine, and an increase of renal activity of xanthine oxidase, and decreases in renal activities of superoxide dismutase and catalase. Peaks in these changes were observed coincidentally on the third day after the administration of the drug was started. Afterwards, these parameters all returned to the control levels. These results strongly suggested that the allopurinol nephrotoxicity was attributed to the increase of lipid peroxidation which had been caused both by an increase in the ability of producing the oxygen radicals and by a decrease in the ability of scavenging the radicals.
为了阐明大鼠中别嘌醇诱导肾毒性的毒性和保护机制，我们研究了血浆肌酐浓度、肾脂质过氧化以及黄嘌呤氧化酶、超氧化物歧化酶和过氧化氢酶的肾活性变化，这些是产生和清除氧自由基的酶促因子。大鼠接受皮下注射剂量为100mg/kg体重的别嘌醇，每天一次，共3天。与对照大鼠相比，在给予别嘌醇的大鼠中观察到以下变化：血浆肌酐浓度升高、肾丙二醛、次黄嘌呤和黄嘌呤含量增加、黄嘌呤氧化酶的肾活性增加以及超氧化物歧化酶和过氧化氢酶的肾活性降低。这些变化的峰值在开始给药后的第三天同时出现。此后，这些参数均恢复到对照水平。这些结果强烈表明，别嘌醇肾毒性归因于脂质过氧化增加，这是由产生氧自由基的能力增加和清除自由基的能力降低共同引起的。
