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Crocin Protects Malathion-Induced Striatal Biochemical Deficits by Inhibiting Apoptosis and Increasing α-Synuclein in Rats’ Striatum

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Abstract

Long-term exposure to organophosphates might result in neurodegenerative diseases, comprising Parkinson’s disease. Malathion is an organophosphate pesticide with high neurotoxicity. Oxidative stress, apoptosis, and α-synuclein accumulation are important underlying mechanisms in Parkinson’s disease. According to studies, crocin, an active constituent of saffron, has anti-apoptotic, anti-inflammatory, and antioxidant properties. Thus, the effect of crocin on malathion-induced striatal biochemical deficits in rats was investigated in this study. Six groups of male Wistar rats were used: 1. control (normal saline); 2. malathion (100 mg/kg/day, i.p.); 3. crocin (10 mg/kg/day, i.p.) + malathion; 4. levodopa (10 mg/kg/day, i.p.) + malathion; 5. crocin (40 mg/kg/day, i.p.); and 6. polyethylene glycol (PEG) (vehicle of levodopa) groups. The drugs were administered for 28 days. The amounts of Bcl-2, Bax, and caspases 3, 8, and 9 proteins in the striatum were measured by western blotting. Also, the amounts of protein and mRNA level of the α-synuclein in striatum tissue were measured by western blotting and RT-qPCR methods. Malathion induced apoptosis by increasing the amount of Bax/Bcl2 ratio and caspases 3 and 9 proteins in rat striatum tissue. It also increased the protein and mRNA level of α-synuclein in striatal tissue. Co-administration of crocin or levodopa with malathion inhibited the toxic effects of malathion on striatal tissue. Crocin ameliorates the neurotoxic effect of malathion by its anti-apoptotic activity and regulating the expression of proteins involved in Parkinson’s disease pathogenesis. As a result, crocin has the potential to be used as a treatment for malathion-induced neurotoxicity.

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Availability of Data and Materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This research was supported by the Pharmaceutical Research Center and Vice-Chancellor of Research, Mashhad University of Medical Sciences (No: 931316).

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Authors and Affiliations

  1. School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Leila Mohammadzadeh

  2. Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahboobeh Ghasemzadeh Rahbardar & Hossein Hosseinzadeh

  3. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Bibi Marjan Razavi & Hossein Hosseinzadeh

  4. Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

    Bibi Marjan Razavi

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  1. Leila Mohammadzadeh
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  2. Mahboobeh Ghasemzadeh Rahbardar
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  3. Bibi Marjan Razavi
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  4. Hossein Hosseinzadeh
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Contributions

HH and BMR were supervisors, designed the work, revised it critically for important intellectual content, and approved the version to be published. LM did the experiment and MGR wrote the manuscript.

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Correspondence to Bibi Marjan Razavi or Hossein Hosseinzadeh.

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All animal studies were carried out in accordance with the norms of the Ethics Committee of Mashhad University of Medical Sciences (No: 931316, 15.03.2017).

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Mohammadzadeh, L., Ghasemzadeh Rahbardar, M., Razavi, B. et al. Crocin Protects Malathion-Induced Striatal Biochemical Deficits by Inhibiting Apoptosis and Increasing α-Synuclein in Rats’ Striatum. J Mol Neurosci 72, 983–993 (2022). https://doi.org/10.1007/s12031-022-01990-3

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