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

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 260-300g were randomly allocated to six groups of control (n = 12), crocin 90mg/kg group (n = 12), METH (n = 12), METH + crocin 30mg/kg (n = 12), METH + crocin 60mg/kg (n = 12), and METH + crocin 90mg/kg (n = 12). METH neurotoxicity was induced by 40mg/kg of METH in four injections (e.g., 4 × 10mg/kg q. 2h, IP). Crocin was intraperitoneally (IP) injected at 30min, 24h, and 48h 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.