D-Allose Ameliorates Cisplatin-Induced Nephrotoxicity in Mice
D-Allose Ameliorates Cisplatin-Induced Nephrotoxicity in Mice
复制标题
DOI：
10.1620/tjem.228.215
复制
发表时间：
2012-11-01
影响因子：
2.2
通讯作者：
Shirakami, Gotaro
中科院分区：
文献类型：
--
作者：
Miyawaki, Yuki;Ueki, Masaaki;Shirakami, Gotaro
顺铂（cis-diaminedichloropatinium II）是一种有效的抗癌药物，广泛用于治疗各种癌症。然而，由于剂量依赖性肾毒性，其治疗用途受到限制。炎症机制可能在顺铂肾毒性的发病机制中起重要作用。D-阿洛糖是一种存在于自然界中的醛己糖，最近已被证明可抑制脓毒症肾脏中炎症介质的产生。本研究旨在探讨D-阿洛糖对顺铂肾毒性的保护作用。顺铂组和顺铂+D-阿洛糖组腹腔注射顺铂（20 mg/kg），对照组注射生理盐水。顺铂注射后立即腹腔注射D-阿洛糖。顺铂注射后72 h测定血清和肾脏肿瘤坏死因子（TNF）-α浓度、肾脏单核细胞趋化蛋白-1（MCP-1;单核细胞趋化因子）、肾功能、组织学变化和肾皮质中性粒细胞浸润。与顺铂组相比，顺铂+D-阿洛糖（400 mg/kg体重）组的血清TNF-α浓度显著降低。与顺铂组相比，顺铂+D-阿洛糖组的肾脏TNF-α和MCP-1浓度显著降低。顺铂+D-阿洛糖组的神经细胞浸润明显低于顺铂组。D-阿洛糖治疗可减轻顺铂引起的肾功能不全和肾小管损伤评分。这些结果表明D-阿洛糖通过抑制肾脏炎症减轻顺铂诱导的肾毒性。因此，D-阿洛糖有可能成为治疗顺铂肾毒性的一种新的候选药物。
Cisplatin (cis-diamminedichloroplatinum II) is a potent antineoplastic agent widely used to treat various forms of cancer. However, its therapeutic use is limited because of dose-dependent nephrotoxicity. Inflammatory mechanisms may play an important role in the pathogenesis of cisplatin nephrotoxicity. D-allose is an aldo-hexose present in nature that recently has been demonstrated to inhibit production of inflammatory mediators in septic kidneys. The purpose of this study was to determine the protective effects of D-allose on cisplatin-induced nephrotoxicity. Cisplatin (20 mg/kg) was administered by intraperitoneal injection to mice in the cisplatin group and the cisplatin plus D-allose group, as was normal saline to control group mice. D-allose was intraperitoneally administered immediately after cisplatin injection. Serum and renal tumor necrosis factor (TNF)-alpha concentrations, renal monocyte chemoattractant protein-1 (MCP-1; a chemotactic factor for monocytes), renal function, histological changes and renal cortex neutrophil infiltration were determined 72 h after cisplatin injection. The serum TNF-alpha concentration in the cisplatin plus D-allose (400 mg/kg body weight) group significantly decreased in comparison with that in the cisplatin group. The renal TNF-alpha and MCP-1 concentrations in the cisplatin plus D-allose group significantly decreased in comparison with those in the cisplatin group. Neutrophil infiltration in the cisplatin plus D-allose group was significantly lower than that in the cisplatin group. Cisplatin-induced renal dysfunction and renal tubular injury scores were attenuated by D-allose treatment. These results reveal that D-allose attenuates cisplatin-induced nephrotoxicity by suppressing renal inflammation. Hence, D-allose may become a new therapeutic candidate for treatment of cisplatin-induced nephrotoxicity.