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Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats

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Abstract

Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100 mg/kg) 30 min after giving CPF (orally, 6.75 mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity.

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Funding

This work was supported by Grants from the Scientific Research Projects Coordination Unit of Atatürk University (Project Code: TSA-2019-7303, Project ID: 7303). Therefore, we are grateful to Atatürk University, Turkey.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Sefa Küçükler

  2. Department of Medical Biochemistry, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Turkey

    Cuneyt Caglayan

  3. Department of Genetics, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Selçuk Özdemir

  4. Department of Pathology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey

    Selim Çomaklı

  5. Department of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey

    Fatih Mehmet Kandemir

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  1. Sefa Küçükler
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  2. Cuneyt Caglayan
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  4. Selim Çomaklı
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SK and FMK designed the research. SK, CC, SÖ, SÇ and FMK conducted experiments. CC, FMK, and SÇ analyzed data. CC wrote the manuscript. All the authors have read and approved the final version for publication.

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Correspondence to Cuneyt Caglayan.

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Küçükler, S., Caglayan, C., Özdemir, S. et al. Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats. Metab Brain Dis 39, 509–522 (2024). https://doi.org/10.1007/s11011-023-01339-8

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