Journal of Molecular Neuroscience

, Volume 67, Issue 1, pp 133–141 | Cite as

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

  • Fateme Ghanbari
  • Mehdi KhaksariEmail author
  • Golamhassan Vaezi
  • Vida Hojati
  • Abdolhossein Shiravi


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.


Hydrogen sulfide Methamphetamine neurotoxicity Apoptosis Neuroinflammation Antioxidant activity 



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

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biology, Damghan BranchIslamic Azad UniversityDamghanIran
  2. 2.Addiction Research CenterShahroud University of Medical SciencesShahroudIran

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