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Crocin Inhibits Apoptosis and Astrogliosis of Hippocampus Neurons Against Methamphetamine Neurotoxicity via Antioxidant and Anti-inflammatory Mechanisms

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Abstract

Methamphetamine (METH) is a stimulant drug, which can cause neurotoxicity and increase the risk of neurodegenerative disorders. The mechanisms of acute METH intoxication comprise intra-neuronal events including oxidative stress, dopamine oxidation, and excitotoxicity. According to recent studies, crocin protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic compound. Accordingly, this study aimed to determine if crocin can protect against METH-induced neurotoxicity. Seventy-two male Wistar rats that weighed 260–300 g were randomly allocated to six groups of control (n = 12), crocin 90 mg/kg group (n = 12), METH (n = 12), METH + crocin 30 mg/kg (n = 12), METH + crocin 60 mg/kg (n = 12), and METH + crocin 90 mg/kg (n = 12). METH neurotoxicity was induced by 40 mg/kg of METH in four injections (e.g., 4 × 10 mg/kg q. 2 h, IP). Crocin was intraperitoneally (IP) injected at 30 min, 24 h, and 48 h after the final injection of METH. Seven days after METH injection, the rats’ brains were removed for biochemical assessment using the ELISA technique, and immunohistochemistry staining was used for caspase-3 and glial fibrillary acidic protein (GFAP) detection. Crocin treatment could significantly increase superoxide dismutase (P < 0.05) and glutathione (P < 0.01) levels and reduce malondialdehyde and TNF-α in comparison with the METH group (P < 0.05). Moreover, crocin could significantly decline the level of caspase-3 and GFAP-positive cells in the CA1 region (P < 0.01). According to the results, crocin exerts neuroprotective effects on METH neurotoxicity via the inhibition of apoptosis and neuroinflammation.

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Authors and Affiliations

  1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

    Monire Shafahi, Golamhassan Vaezi, Hooman Shajiee & Shahram Sharafi

  2. Addiction Research Center, Shahroud University of Medical Sciences, Shahroud, Iran

    Mehdi Khaksari

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  1. Monire Shafahi
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  2. Golamhassan Vaezi
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  3. Hooman Shajiee
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Correspondence to Mehdi Khaksari.

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Shafahi, M., Vaezi, G., Shajiee, H. et al. Crocin Inhibits Apoptosis and Astrogliosis of Hippocampus Neurons Against Methamphetamine Neurotoxicity via Antioxidant and Anti-inflammatory Mechanisms. Neurochem Res 43, 2252–2259 (2018). https://doi.org/10.1007/s11064-018-2644-2

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  • DOI: https://doi.org/10.1007/s11064-018-2644-2

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