al-Harbi M M, Osman A M, al-Gharably N M, al-Bekairi A M, al-Shabanah O A, Sabah D M, Raza M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Chemotherapy. 1995 Nov-Dec;41(6):448-54. doi: 10.1159/000239381.
Biochemical and histological evaluations of the effects of the iron chelator desferrioxamine on the nephrotoxicity induced by cisplatin in normal rats were carried out. A single dose of cisplatin (7.5 mg/kg, intravenously) caused nephrotoxicity that manifested biochemically as an elevation of blood urea nitrogen, serum creatinine and an increase in the kidney weight as a percent of body weight. Moreover, severe decreases in serum calcium and albumin were observed. Histopathological examination of kidney tissue revealed tubular necrosis with sloughing of tubular epithelium. Desferrioxamine treatment (250 mg/kg, intraperitoneally) 30 min before cisplatin administration does not protect the kidney from the damaging effects of cisplatin. A greater increase in blood urea nitrogen, serum creatinine and kidney weight was observed with significant tubular necrosis and a mild lymphocytic infiltrate. Desferrioxamine pretreatment decreased the lipid peroxidation induced by cisplatin but at the same time increased nonprotein sulfhydryl (-SH) concentrations in the kidney tissue. The findings of this study suggest that lipid peroxidation is not the main cause of cisplatin-induced nephrotoxicity and that desferrioxamine which was useful for prevention of cardiac and hematological damage induced by doxorubicin, aggrevated the cisplatin-induced nephrotoxicity. More investigations are needed to establish a definite assessment of its selectivity.
开展了铁螯合剂去铁胺对顺铂诱导的正常大鼠肾毒性影响的生化和组织学评估。单次静脉注射顺铂（7.5毫克/千克）会引起肾毒性，生化表现为血尿素氮、血清肌酐升高，肾脏重量占体重的百分比增加。此外，还观察到血清钙和白蛋白严重降低。肾脏组织的组织病理学检查显示肾小管坏死，伴有肾小管上皮脱落。在顺铂给药前30分钟腹腔注射去铁胺（250毫克/千克）并不能保护肾脏免受顺铂的损伤作用。观察到血尿素氮、血清肌酐和肾脏重量有更大幅度的增加，伴有明显的肾小管坏死和轻度淋巴细胞浸润。去铁胺预处理降低了顺铂诱导的脂质过氧化，但同时增加了肾脏组织中非蛋白巯基（-SH）的浓度。本研究结果表明，脂质过氧化不是顺铂诱导肾毒性的主要原因，而去铁胺虽对预防阿霉素诱导的心脏和血液学损伤有用，但却加重了顺铂诱导的肾毒性。需要更多研究来确定其选择性的明确评估。
