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

Abstract

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.

Renoprotective effects of angiotensin receptor blocker and stem cells in acute kidney injury: Involvement of inflammatory and apoptotic markers

“…Infiltration of damaged renal tissue with inflammatory cells is characteristic for CDDP-induced nephrotoxicity. 20 Our experiment showed a significant elevation of renal TNF-a and MCP-1 gene expressions in CDDP group when compared to the normal group and this findings is in accordance with the study of Ueki et al 20 who reported a significant elevation of renal TNF-a and MCP-1 after CDDP injection.…”

“…18,19 Concerning inflammation, it was reported that TNF-a is a proinflammatory cytokine that acts as an important mediator of CDDP-induced inflammatory tissue damage. 20 It is able to induce direct renal injury and causes induction of apoptosis and necrotic cell death. 21 TNF-a also stimulates the release of other cytokines and chemokines, such as MCP-1, 22 which attracts a variety of cells including leukocytes, monocytes and natural killer cells.…”

“…Previous studies demonstrated that amelioration of CDDP nephrotoxicity can be achieved by inhibition of TNF-a production and NF-jB activation. 20,23 Therefore, the modulation of renal inflammatory reactions and apoptotic pathways after CDDP injection may help to prevent CDDP-induced nephrotoxicity. 20 Our study reported that candesartan reduced the renal TNF-a and MCP-1 levels and renal expression of NF-jB in CDDP-treated rats when compared to the normal rats.…”

“…20,23 Therefore, the modulation of renal inflammatory reactions and apoptotic pathways after CDDP injection may help to prevent CDDP-induced nephrotoxicity. 20 Our study reported that candesartan reduced the renal TNF-a and MCP-1 levels and renal expression of NF-jB in CDDP-treated rats when compared to the normal rats. Conceding with our findings, candesartan suppressed the renal MCP-1 and NF-jB in a model of chronic kidney disease.…”

Tribulus terrestris Hydroalcoholic Extract Effect on Cisplatin-Induced Apoptosis in Mice Kidney

“…A single dose of CP caused apoptosis in kidney. It seems that inflammatory responses with regard to the weight of animals are acute consequence of CIS administration that occurs during 3-4 days after exposure (Ueki et al, 2013). In vivo administration of nephrotoxic doses of CP produces a large increase in apoptosis in the kidney (Ramesh & Reeves, 2004).…”