Zingerone protects against cisplatin-induced oxidative damage in the jejunum of Wistar rats

Cisplatin (cis-diamminedichloroplatinum (II) (CDDP)) is a commonly used chemotherapeutic drug for the treatment of numerous forms of cancer, but it has marked adverse effects, namely nephrotoxicity, hepatotoxicity, ototoxicity, neurotoxicity, diarrhoea etc. CDDP-induced emesis and diarrhoea are also noticeable toxicities that may be due to intestinal injury. Zingerone; a phenolic alkanone, one of the active components of ginger, possesses multiple biological activities, such as antioxidant and antiinflammatory properties. In the present study, we investigated the protective effect of zingerone against CDDP-induced jejunal toxicity. Animals were divided into five groups I-IV (n=6). Group II, III and IV received single intraperitoneal administration of CDDP at 7.5 mg/kg body weight on day 14. Animals of group II and III received oral treatment of zingerone at doses of 25 and 50 mg/kg body weight respectively for 14 consecutive days. While groups I was given distilled water 5 ml/kg body weight for 14 days. All the animals were killed after 24 h of CDDP injection. Zingerone ameliorated CDDP-induced lipid peroxidation, increase in xanthine oxidase activity, glutathione depletion, decrease in antioxidant and phase-II detoxifying enzyme activities. Zingerone attenuated CDDP-induced nuclear factor (NF-kappa B) activation, enhanced levels of TNF-alpha and Nitrite. The results showed that zingerone had not only the antioxidant effect by suppression of ROS, but also antiinflammatory effects by suppression of NF-kappa B activation. In addition, zingerone treatment suppressed gene activation of pro-inflammatory cytokine, TNF-alpha, which was up-regulated with CDDP administration through NF-kappa B activation. These experiments strongly indicate that zingerone treatment exercises a protective efficacy by suppressing both oxidative stress and inflammation through the modulation of key pro-inflammatory cytokine and transcription factors.