Neuroprotective potential of linagliptin against mancozeb induced neurotoxicity

Abstract Background 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.