The research investigates the neuroprotective effects of Linagliptin (Lina), a dipeptidyl peptidase-4, against the neurotoxic impacts of Mancozeb (MNZ), which is known to cause cognitive deficits and oxidative stress. Methods: The study involved six groups of rats, with behavioral assessments conducted through various tests such as the open field test, rotarod test, and passive avoidance test. Biochemical analyses measured total thiols (TT), thiobarbituric acid-reactive substances (TBARS), and antioxidant enzyme activities, alongside inflammatory markers like tumour necrosis factor alpha, nitric oxide, interleukin-6, and interleukin-1β.Results: Results indicated that MNZ increased anxiety behaviors, impaired coordination, and reduced memory retention, while Lina reversed these adverse effects.
MNZ significantly decreased TT levels and antioxidant enzyme activities, while increasing TBARS, indicating oxidative damage. Conversely, Lina mitigated these effects, enhancing enzyme functions. Additionally, MNZ elevated inflammatory markers, which were reduced with Lina treatment.
The restoration of Acetylcholinesterase activity further supports Lina’s potential in counteracting MNZ toxicity.Conclusion: Overall, the findings suggest that Lina effectively protects against MNZ-induced neurotoxicity by reducing oxidative stress, enhancing antioxidant activities, and lowering pro-inflammatory cytokines. This research was supported by Ahvaz Jundishapur University of Medical Sciences (TRC-0236). Department of Pharmacology and Toxicology, School of Pharmacy, Lorestan University of Medical Sciences, Khorramabad, Iran Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Maryam Shirani, Mohammad Javad Khodayar & Soheila Aminzadeh Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Physiology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Cancer , Environmental and Petroleum Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran Department of Physiology, Medicine Faculty, Ahvaz Islamic Azad University, Ahvaz, Iran The authors declare no competing interests.
The Animal Ethics Committee at Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran approved the protocol with the reference number IR.AJUMS.ABHC.REC.1402.090. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
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Shariati, S., Shirani, K., Shirani, M. et al. Neuroprotective potential of linagliptin against mancozeb induced neurotoxicity. Sci Rep (2026). https://doi.org/10.1038/s41598-026-72470-6 DOI: https://doi.org/10.1038/s41598-026-72470-6
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