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Maintenance of mitochondrial function by sinapic acid protects against tramadol-induced toxicity in isolated mitochondria obtained from rat brain

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Abstract

It is reported that tramadol can induce neurotoxic effects with the production of DNA damage, mitochondrial dysfunction, and oxidative stress. The current study aimed to evaluate the potential role of mitochondrial impairment in the pathogenesis of tramadol-induced neurotoxicity, and protective effect of sinapic acid (SA) against it in isolated mitochondria from rat brain. Mitochondria were isolated and were incubated with toxic concentrations (100 μM) of tramadol and then cotreated with tramadol + SA (10, 50, and 100 μM). Biomarkers of mitochondrial toxicity including succinate dehydrogenases (SDH) activity, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), GSH depletion, and mitochondrial swelling were assessed. Our results showed a significant decrease in SDH activity, and a significant increase in ROS, LPO, GSH depletion, MMP collapse, and mitochondrial swelling was detected in tramadol group. We observed that 50 and 100 μM SA cotreatment for 1 h efficiently ameliorated tramadol-caused damage in mitochondrial dysfunction, accumulation of ROS, LPO, GSH depletion, depolarization of mitochondrial membrane potential, and mitochondrial swelling. These data suggest that mitochondrial impairment and oxidative stress are mechanisms involved in the pathogenesis of tramadol-induced neurotoxicity. Also, results indicate that SA antagonizes against tramadol-induced mitochondrial toxicity and suggest SA may be a preventive/therapeutic agent for tramadol-induced neurotoxicity complications.

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Data availability

The datasets generated during and/or analyzed during this study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Ardabil of Medical Sciences, Deputy of Research (approval code: IR.ARUMS.AEC.1401.014).

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Authors and Affiliations

  1. Traditional Medicine and Hydrotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

    Mohammad Shabani, Saleh Khezri & Ahmad Salimi

  2. Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

    Mohammad Shabani, Saleh Khezri & Ahmad Salimi

  3. Department of Addiction Studies, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Zhaleh Jamali

  4. Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran

    Zhaleh Jamali

  5. Students Research Committee, Faculty of Pharmacy, Ardabil University of Medical Sciences, Ardabil, Iran

    Aida Naserian

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  1. Mohammad Shabani
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Contributions

AS conceived and designed research, analyzed data, and wrote the manuscript. MS, ZJ, AN, and SK conducted experiments. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Ahmad Salimi.

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Ethical approval

The Ethics Committee of the Ardabil University of Medical Sciences reviewed and approved the protocols for used animal in the current study (Code: IR.ARUMS.AEC.1401.014).

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The authors declare no competing interests.

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Shabani, M., Jamali, Z., Naserian, A. et al. Maintenance of mitochondrial function by sinapic acid protects against tramadol-induced toxicity in isolated mitochondria obtained from rat brain. Naunyn-Schmiedeberg's Arch Pharmacol 397, 889–897 (2024). https://doi.org/10.1007/s00210-023-02648-6

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