D-Ribose Ameliorates Cisplatin-Induced Nephrotoxicity by Inhibiting Renal Inflammation in Mice

D-Ribose Ameliorates Cisplatin-Induced Nephrotoxicity by Inhibiting Renal Inflammation in Mice

MASAAKI UEKI,^1,2 MASAKI UENO,³ JUN MORISHITA² and NOBUHIRO MAEKAWA²

¹Department of Anesthesia, Nishiwaki Municipal Hospital, Nishiwaki, Hyogo, Japan
²Department of Anesthesia and Perioperative Medicine, Kobe University, Kobe, Hyogo, Japan
³Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan

Cisplatin is one of the most potent chemotherapeutic anticancer drugs, but it can produce side effects such as nephrotoxicity. Inflammatory cytokines, chemokines and adhesion molecules have important roles in the pathogenesis of cisplatin-induced nephrotoxicity. D-Ribose is a naturally occurring five-carbon monosaccharide that is found in all living cells, and has anti-inflammatory effects in renal ischemia/reperfusion injury. The purpose of this study was to determine the protective effects of D-ribose on cisplatin-induced nephrotoxicity. Forty-eight mice were randomly divided into four groups: control, cisplatin, cisplatin + ribose, and ribose. Mice were given cisplatin (20 mg/kg body weight, intraperitoneally) with or without D-ribose (400 mg/kg body weight, intraperitoneally, immediately after cisplatin injection). At 72 h after cisplatin injection, we measured serum and renal tumor necrosis factor (TNF)-α and renal monocyte chemoattractant protein (MCP)-1 concentrations by enzyme-linked immunosorbent assay; renal expression of intercellular adhesion molecule (ICAM)-1 mRNA by real-time polymerase chain reaction; serum blood urea nitrogen and creatinine; and histological changes. Cisplatin increased serum and renal TNF-α concentrations, renal MCP-1 concentration, and renal ICAM-1 mRNA expression. Treatment with D-ribose attenuated the increase in serum and renal TNF-α concentrations, renal MCP-1 concentration, and renal ICAM-1 mRNA expression. Consequently, cisplatin-induced renal dysfunction and renal tubular necrosis were attenuated by D-ribose treatment. This is believed to be the first time that protective effects of D-ribose on cisplatin-induced nephrotoxicity via inhibition of inflammatory reactions have been investigated. Thus, D-ribose may become a new therapeutic candidate for the treatment of cisplatin-induced nephrotoxicity.

keywords —— chemokine; cisplatin; D-ribose; nephrotoxicity; tumor necrosis factor α

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Tohoku J. Exp. Med., 2013, 229, 195-201

Correspondence: Masaaki Ueki, Department of Anesthesia, Nishiwaki Municipal Hospital, 652-1 Shimotoda, Nishiwaki, Hyogo 677-0043, Japan.

e-mail: mueki1961@gmail.com