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Resveratrol alleviates inflammatory hyperalgesia by modulation of reactive oxygen species (ROS), antioxidant enzymes and ERK activation

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Abstract

Objectives

Impact of ROS in development of hyperalgesia has recently motivated scientists to focus on ROS as novel target of anti-hyperalgesic interventions. However, role of ROS in molecular signaling of hyperalgesia is still poorly understood. The present study is aimed to analyze the effect of dietary antioxidant resveratrol on antioxidant defense system, ROS level and TNFR1–ERK signaling pathway during early and late phase of inflammatory hyperalgesia.

Methods and materials

Hyperalgesia was assessed by paw withdrawal latency test in complete Freund’s adjuvant-induced hyperalgesic rats. Activities of antioxidant enzymes were measured by in-gel assays, ROS level was measured by DCFH2DA, and expression of pERK, ERK and TNFR1 was estimated by Western blotting.

Results

Anti-hyperalgesic effect of resveratrol was observed by paw withdrawal latency test. ROS level was increased in paw skin as well as spinal cord during early phase which was further increased in paw skin, but remained constant in spinal cord up to late phase. Resveratrol differentially regulated the activities of SOD, catalase and GPx in paw skin as well as spinal cord of hyperalgesic rats in both phases. Activities were normalized back showing anti-hyperalgesic effect of resveratrol. Upregulated ERK signaling was modulated by resveratrol, whereas TNFR1 level remained unchanged.

Conclusion

Overall results suggest that resveratrol alleviates inflammatory hyperalgesia by downregulation of ERK activation, modulation of ROS and differential regulation of antioxidant enzymes during early and late phases.

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Acknowledgements

Authors are thankful to DRDO, India, for financial support (Grant No. ERIP/ER/1003851/M/01/1336). AKS thanks UGC, India, for JRF and SRF. Financial support by DST-FIST and UGC-CAS program to Department of Zoology, BHU, and UGC-UPE to BHU is also acknowledged.

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Authors and Affiliations

  1. Biochemistry and Molecular Biology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, India

    Ajeet Kumar Singh & Manjula Vinayak

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  1. Ajeet Kumar Singh
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  2. Manjula Vinayak
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Contributions

AKS has executed the experiments. MV and AKS have contributed in conception of the study, design of experiments, analysis and interpretation of data and finalizing the manuscript. Both authors read and approved the final manuscript.

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Correspondence to Manjula Vinayak.

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Responsible Editor: John Di Battista.

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Singh, A.K., Vinayak, M. Resveratrol alleviates inflammatory hyperalgesia by modulation of reactive oxygen species (ROS), antioxidant enzymes and ERK activation. Inflamm. Res. 66, 911–921 (2017). https://doi.org/10.1007/s00011-017-1072-0

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  • DOI: https://doi.org/10.1007/s00011-017-1072-0

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