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Disruptions in nitric oxide homeostasis, lipid peroxidation-derived oxidative stress, and antioxidant defense mechanisms in spinal cord injury: elucidating biomolecular correlates of disease severity

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Abstract

Spinal cord injury (SCI) is a debilitating condition characterized by irreversible neurological deficits resulting from primary mechanical damage followed by a complex cascade of secondary injuries. Among the key molecular mechanisms driving secondary damage are oxidative stress (OS), nitric oxide (NO) homeostasis disruptions, and impaired antioxidant defense systems. This review elucidates the critical interplay between reactive oxygen and nitrogen species, lipid peroxidation (LPO)-derived aldehydes such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and the roles of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Particular focus is placed on the dual role of NO as both a neuroprotective and neurotoxic agent, influenced mainly by its source and interaction with superoxide to form peroxynitrite (ONOO⁻). The paper also highlights the regulatory functions of trace elements like zinc, selenium, copper, and magnesium in modulating oxidative responses and recovery. Also, the nuclear factor erythroid 2 related factor 2 (Nrf2) pathway is discussed as a vital modulator of antioxidant gene expression. Understanding the dynamic cross-talk between NO signaling, LPO, and antioxidant mechanisms provides valuable insights into the molecular pathophysiology of SCI and unveils potential therapeutic targets aimed at mitigating oxidative damage, promoting neuroprotection, and enhancing functional recovery.

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Data availability

The data supporting the findings of this study are based on previously published literature and are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to express their sincere gratitude to Era University, Lucknow, and Isabella Thoburn College, Lucknow, for providing institutional support and access to academic resources that made this work possible. Special thanks to the Department of Biotechnology and the Department of Zoology for their encouragement and technical assistance during the course of this study.

Funding

No external funding was received for the preparation of this review article.

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Authors and Affiliations

  1. Department of Biotechnology, Era University, Lucknow, India

    Mohd Mursal, Irfan Hasan, Babita Tiwari & Ghizal Fatima

  2. Department of Zoology, Toxicology Unit, Isabella Thoburn College, Lucknow, India

    Rajesh K. Srivastava

  3. Department of Physical Medicine and Rehabilitation, King George’s Medical University, Lucknow, India

    Ganesh Yadav

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  1. Mohd Mursal
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  2. Irfan Hasan
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  3. Babita Tiwari
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  4. Rajesh K. Srivastava
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  5. Ganesh Yadav
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  6. Ghizal Fatima
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Contributions

M.M. conceptualized the study, developed the methodology, conducted the literature search, prepared tables and figures, wrote the original draft, and critically revised the manuscript. I.H. contributed to data curation, analysis of molecular mechanisms, and manuscript editing. B.T. validated the data, interpreted the findings, and formatted the manuscript. R.K.S. provided supervision, expert input on redox biology and toxicology, and critically reviewed the manuscript. G.Y. interpreted the medical context, validated the clinical relevance, and proofread the manuscript. G.F. handled project administration, performed the final manuscript review, supervised the overall work, and corresponded with the journal.

Corresponding author

Correspondence to Ghizal Fatima.

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Mursal, M., Hasan, I., Tiwari, B. et al. Disruptions in nitric oxide homeostasis, lipid peroxidation-derived oxidative stress, and antioxidant defense mechanisms in spinal cord injury: elucidating biomolecular correlates of disease severity. Mol Biol Rep 52, 969 (2025). https://doi.org/10.1007/s11033-025-11091-0

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