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 anti-inflammatory 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-κB) activation, enhanced levels of TNF-α and Nitrite. The results showed that zingerone had not only the antioxidant effect by suppression of ROS, but also anti-inflammatory effects by suppression of NF-κB activation. In addition, zingerone treatment suppressed gene activation of pro-inflammatory cytokine, TNF-α, which was up-regulated with CDDP administration through NF-κB 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.