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

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Abstract

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.

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Acknowledgments

The Authors are thankful to Vice Chancellor (Dr Tej Partab) for providing facilities to complete this research work.

Ethical statement

All procedures for using experimental animals were checked and permitted by the ‘Institutional Animal Ethical Committee’ that is fully accredited by the Committee for Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

Conflict of Interest

The authors declare that they have no conflict interests.

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Authors and Affiliations

  1. Molecular Biology Lab, Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, Sheri Kashmir University of Agricultural Science & Technology (SKUAST-K), Alustang, Shuhama, Srinagar, J&K, India, 190006

    Muneeb U. Rehman, Bilal Ahmad, Ahmad Arif, Rahil Razzaq, Showkat Ahmad Bhat, Sumaira Bashir, Ovais Shabir, Insha Amin & Manzoor ur Rahman Mir

  2. Department of Pharmaceutical sciences, Faculty of Applied Sciences, University of Kashmir, Hazratbal, Srinagar, J&K, India, 190006

    Muneeb U. Rehman, Adil Farooq, Mubashir Masoodi & Mohammed Yaseen Shah

  3. Forest Biotech Lab, Department of Forest Management, Faculty of Forestry, University Putra Malaysia, Serdang, Selangor, Malaysia, 4340

    Saiema Rasool

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  1. Muneeb U. Rehman
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  2. Bilal Ahmad
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  3. Ahmad Arif
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Correspondence to Muneeb U. Rehman.

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Rehman, M.U., Ahmad, B., Arif, A. et al. Zingerone protects against cisplatin-induced oxidative damage in the jejunum of Wistar rats. Orient Pharm Exp Med 15, 199–206 (2015). https://doi.org/10.1007/s13596-015-0187-5

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