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Hydrogen Sulfide Protects Hippocampal Neurons Against Methamphetamine Neurotoxicity Via Inhibition of Apoptosis and Neuroinflammation

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Abstract

Methamphetamine (METH) known as a highly neurotoxic compound associated with irreversible brain cell damage that results in neurological and psychiatric abnormalities. The mechanisms of METH intoxication mainly involve intraneuronal events including oxidative stress, excitotoxicity, and dopamine oxidation. Based on recent studies, H2S can protect neurons through anti-inflammatory, antioxidant, and antiapoptotic mechanisms. Therefore, we aimed to study the effects of protection of H2S against METH neurotoxicity. The 72 male Wistar rats were randomly allocated into six groups: control (n, 12), H2S (n, 12), METH (n, 12), METH + H2S 1 mg/kg (n, 12), METH + H2S 5 mg/kg (n, 12), and METH + H2S 10 mg/kg (n, 12) groups, (NaHS as a H2S donor; 1, 5, 10 mg/kg). METH neurotoxicity was induced by 40 mg/kg of METH in four intraperitoneal (IP) injections (e.g., 4 × 10 mg/kg q. 2 h, IP). NaHS was administered at 30 min, 24 h, and 48 h after the final injection of METH. Seven days after METH injection, the brains were removed for biochemical assessments, glial fibrillary acidic protein (GFAP), and caspase-3 immunohistochemistry staining. H2S treatment could significantly increase both superoxide dismutase and glutathione (P < 0.01), and a reduction was observed in malondialdehyde (P < 0.05) and TNF-α (P < 0.01) versus the METH group. Moreover, H2S could significantly decrease caspase-3 and GFAP-positive cells in the CA1 region of the hippocampus (P < 0.01) compared to the METH group. According to the findings, H2S makes significant neuroprotective impacts on METH neurotoxicity due to its antioxidant and anti-inflammatory activities.

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Acknowledgements

The authors are very thankful to Pirasteh Norozi, Mahnaz Mesripour Alavije, and Mohammad Taghi Rahimi for their kind and helpful collaborations.

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Authors and Affiliations

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

    Fateme Ghanbari, Golamhassan Vaezi, Vida Hojati & Abdolhossein Shiravi

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

    Mehdi Khaksari

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  1. Fateme Ghanbari
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  2. Mehdi Khaksari
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Correspondence to Mehdi Khaksari.

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Ghanbari, F., Khaksari, M., Vaezi, G. et al. Hydrogen Sulfide Protects Hippocampal Neurons Against Methamphetamine Neurotoxicity Via Inhibition of Apoptosis and Neuroinflammation. J Mol Neurosci 67, 133–141 (2019). https://doi.org/10.1007/s12031-018-1218-8

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