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Attenuation of vincristine-induced neuropathy by synthetic cyclohexenone-functionalized derivative in mice model

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Abstract

Vincristine (VCR) is a well-known anticancer drug which frequently induced painful neuropathy and impairs the quality of life of patients. The present study was designed to investigate the alleviative potential of a novel cyclohexenone derivative (CHD), i.e., ethyl 6-(4-methoxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate, against VCR-induced neuropathic pain in mice model. VCR was administered intraperitoneally for 10 days in two cycles to induce neuropathic pain. Static and dynamic mechanical allodynia was evaluated using von Frey hair filaments and cotton buds, respectively. Paw thermal hyperalgesia was determined through a hot plate analgesiometer. The tail cold immersion hyperalgesia and paw cold allodynia were determined by available standard protocols. The formalin nociception was induced via subplantar injection of formalin. The antioxidant potential was evaluated via 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. The outcome of this study revealed that CHD (30–45 mg/kg) and gabapentin (75 mg/kg) significantly enhanced the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in static and dynamic allodynia, respectively, and increased the PWL in thermal hyperalgesia and tail withdrawal latency (TWL) as compared to the VCR-treated group. CHD significantly augmented the paw withdrawal duration (PWD) in paw cold allodynia, while the same compound only increased the paw elevation and paw licking in the delayed phase of formalin nociception. Moreover, CHD significantly inhibited the DPPH free radical scavenging action (IC50 = 56), butylated hydroxytoluene (BHT) (IC50 = 39), and ascorbic acid (IC50 = 2.93). In conclusion, CHD exhibited a profile of potential attenuative effect against the VCR-induced neuropathic pain which might be attributed to its possible antinociceptive and antioxidant effect.

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Acknowledgments

The selected cyclohexenone compound has been synthesized as part of a series of compounds and their structures were confirmed by Dr. Rasool Khan, Associate Professor, Institute of Chemical Science, University of Peshawar. We are grateful to him for providing a series of compounds and after preliminary study; we have selected the cited CHD compound for neuropharmacological study.

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Authors and Affiliations

  1. Department of Pharmacy, University of Peshawar, Peshawar, 25120, Pakistan

    Jawad Khan, Gowhar Ali & Rahim Ullah

  2. Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan

    Rasool Khan & Salim Ullah

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  1. Jawad Khan
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Contributions

GA initiated the research project and directed the research scholars as supervisor in conducting pharmacological experiments. GA critically evaluated the contents of the final version of the manuscript. JK accomplished the pharmacological experiments and performed calculations and statistical analysis. He developed the preliminary draft of the manuscript. RU helped JK in the conduction of the experiments. SU conducted experiment-related synthesis and structure confirmation under the supervision of RK. RK helped in planning and supervising the experiments related to chemistry of our selected compounds (chemistry structural data not included in this manuscript). All authors read and approved the final manuscript.

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Correspondence to Gowhar Ali.

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Khan, J., Ali, G., Khan, R. et al. Attenuation of vincristine-induced neuropathy by synthetic cyclohexenone-functionalized derivative in mice model. Neurol Sci 40, 1799–1811 (2019). https://doi.org/10.1007/s10072-019-03884-6

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  • DOI: https://doi.org/10.1007/s10072-019-03884-6

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