Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats
Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats
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DOI：
10.1007/s00204-005-0648-6
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发表时间：
2005-08-01
影响因子：
6.1
通讯作者：
Maruyama, T
中科院分区：
文献类型：
--
作者：
Uehara, T;Watanabe, H;Maruyama, T
本研究以顺铂(CDDP)为对照，研究了抗肿瘤铂复合体奈达铂(NDP)对不同年龄大鼠的肾毒性。给8、11或15周龄的雄性和雌性SD大鼠单次静脉注射NDP 15 mg/kg或CDDP 7.5 mg/kg，10天后处死。观察到两种药物的体重下降与年龄直接相关。CDDP可显著增加尿NAG、γ-GTP、LDH和蛋白的排泄，高峰出现在第4天，完全或部分恢复到第7天；NDP使NAG、LDH和蛋白质排泄增加，但幅度较小，且这些升高通常对女性更为明显。CDDP使各年龄组男性和女性在尸检时的血肌酐和BUN升高。NDP治疗后，除15周龄大鼠外，未见明显变化。这些结果还表明，NDP的肾毒性比CDDP小。顺铂处理组大鼠肾皮质和皮质髓质区近端肾小管病变明显，乳头状病变较小。另一方面，NDP所致的肾毒性表现为肾乳头和覆盖乳头的集合管上皮细胞坏死或增生，可见透明小滴改变(电子显微镜下可见溶酶体增生)。皮质部病变，表现为轻微的管状扩张，仅在有乳头状病变的动物中发现。综上所述，NDP是一种有希望的第二代铂配合物，具有较低的肾毒性。
The present study was designed to characterize the nephrotoxicity induced by the antineoplastic platinum complex nedaplatin (NDP) in rats of different ages in comparison with cisplatin (CDDP). A single dose of 15 mg/kg NDP or 7.5 mg/kg CDDP was administered intravenously to 8-, 11-, or 15-week-old male and female SD rats, which were then sacrificed after ten days. Body weight decreases were observed for both drugs, in direct relation to age. CDDP treatment markedly increased urinary excretion of NAG, gamma-GTP, LDH and protein, with peaks on day 4 and complete or partial recovery on day 7; NDP increased NAG, LDH and protein excretion, but to a lesser extent, and these elevations were generally more marked for females. CDDP increased plasma creatinine and BUN in males and females of all age groups at necropsy. No apparent changes were seen following NDP treatment except in the 15-week-old rats. These results also show that NDP is less nephrotoxic than CDDP. CDDP-treated rats showed remarkable proximal tubular lesions in the renal cortex and corticomedullary region, and the papillary lesions were minor. On the other hand, the NDP-induced nephrotoxicity was morphologically characterized by hyaline droplet changes (electron microscopically, hyperplasia of lysosomes), necrosis or hyperplasia of the collecting duct epithelium in the renal papilla and the epithelium covering the papilla. Cortical lesions, indicated by slight tubular dilatation, were found only in the animals with papillary lesions. In summary, NDP is a promising second-generation platinum complex with reduced nephrotoxicity.