D-Allose Ameliorates Cisplatin-Induced Nephrotoxicity in Mice

D-Allose Ameliorates Cisplatin-Induced Nephrotoxicity in Mice

YUKI MIYAWAKI,¹ MASAAKI UEKI,² MASAKI UENO,³ TAKEHIKO ASAGA,¹ MASAAKI TOKUDA⁴ and GOTARO SHIRAKAMI¹

¹Department of Anesthesiology, Faculty of Medicine, Kagawa University, Kagawa, Japan
²Division of Intensive Care Medicine, Kobe University Hospital, Kobe, Japan
³Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan
⁴Department of Cell Physiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

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.

keywords —— acute kidney injury; cisplatin; D-allose; monocyte chemoattractant protein-1; tumor necrosis factor alpha

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Tohoku J. Exp. Med., 2012, 228, 215-221

Correspondence: Yuki Miyawaki, Department of Anesthesiology, Faculty of Medicine, Kagawa University, 1750-Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.

e-mail: yukiyuki@med.kagawa-u.ac.jp