D-allose ameliorates cisplatin-induced nephrotoxicity in mice.
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.
Department of Anesthesiology, Faculty of Medicine, Kagawa University, Kagawa, Japan. yukiyuki@med.kagawa-u.ac.jp
Yuki
Y
Miyawaki
Masaaki
M
Ueki
Masaki
M
Ueno
Takehiko
T
Asaga
Masaaki
M
Tokuda
Gotaro
G
Shirakami
D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D002945:Cisplatin; D005947:Glucose / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; C002055:allose; D005947:Glucose; D002945:Cisplatin