Cisplatin (cis-diaminedichloroplatinum II, CDDP) is extensively used for the treatment of several cancers. Its major side effect; namely, nephrotoxicity, is a dose-limiting factor in CDDP therapy.1) The exact mechanisms of nephrotoxicity induced by CDDP are still not fully elucidated. However, lipid peroxidation and free radical generation in the renal tubular cells have been suggested to be responsible for CDDP-induced renal failure.2) Zhang et al. showed that CDDP significantly depletes glutathione (GSH) and increases lipid peroxidation in the mitochondria prepared from the rat renal cortical slices.3) In addition, the activities of superoxide dismustase (SOD) and catalase in the rat kidney tissues are significantly suppressed by CDDP. 4)Capsaicin (Cap) is the major pungent ingredient of hot red peppers. It has been used as a tool in the study of pain sensations which are caused by stimulation of Cap receptor or vanilloid receptor 1, an ion channel protein expressed by nociceptive primary afferent neurons. 5,6) On the other hand, Cap potentially inhibits the peroxidation of various lipids [7][8][9][10] and generates reactive oxygen species in rat peritoneal macrophages.11) However, the mechanism responsible for the potent inhibitory effects of Cap on lipid peroxidation in vivo is still unclear.Several studies have examined the effects of decreased lipid peroxidation and nephrotoxicity induced by CDDP using various agents including antioxidants. [12][13][14] The purpose of the present study was to investigate whether the administration of Cap exerts any protective effect against cisplatin-induced lipid peroxidation and nephrotoxicity in rats. MATERIALS AND METHODS ChemicalsCap with a purity of 98.6% was kindly supplied by Maruishi Pharmaceutical Co., Ltd. (Osaka, Japan). CDDP was purchased from Sigma (MO, U.S.A.). All other chemicals and reagents used were of analytical grade.Animals Male Sprague-Dawley rats weighing 200 to 250 g were purchased from Nippon SLC Inc. (Shizuoka, Japan). The rats had free access to standard rat chow and water ad libitum, were individually housed in metal cages, and kept in a room maintained at 23Ϯ2°C with a 12 h/12 h light/dark cycle. The study adhered to the guidelines of Osaka University of Pharmaceutical Sciences for the experimental use of animals.Animal Treatments The rats were divided at random into 4 groups of 4 or 5 animals each. The first group (control) received a vehicle (5% carboxymethyl cellulose sodium solution (CMC-Na), 5 ml/kg body wt., p.o.) used for Cap. The second group received Cap (10 mg/kg/d, p.o.) in 5% CMC-Na (5 ml/kg), and the third received 5% CMC-Na for 6 consecutive days injected with CDDP (5 mg/kg in physiological saline solution, i.p.). The fourth group received Cap (10 mg/kg/d, p.o.) in 5% CMC-Na for 6 consecutive days after CDDP injection (5 mg/kg, i.p.). For all groups, Cap or vehicle was given twice daily. The selected Cap concentration and the dose administration schedule without inducing any rat intestinal damage were chosen using data from our p...

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Recent studies suggest that capsaicin (Cap), a major constituent of hot pepper, may affect the function and permeability of the intestinal mucosa in vitro. However, the relationships between the dose of Cap and the barrier and/or transporter functions on intestinal epithelial cells are unknown. The aim of this study was to investigate whether Cap initiates cellular injury and alter epithelial permeability in Caco-2 cells. Cellular toxicity, as measured using a lactate dehydrogenase release assay, was not observed at high concentrations of Cap (up to 300 m mM).