Activation of MIP-2 and MCP-5 Expression in Methylmercury-Exposed Mice and Their Suppression by N-Acetyl-L-Cysteine.

Muflihatul Muniroh, Ainun Rahmasari Gumay, Darmawati Ayu Indraswari, Yuriz Bahtiar, Hardian Hardian, Saekhol Bakri, Nani Maharani, Vega Karlowee, Chihaya Koriyama, Megumi Yamamoto

Neurotoxicity research 2020 Apr

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Methylmercury (MeHg) is a well-known neurotoxin of the central nervous system (CNS). Neuroinflammation is one of the main pathways of MeHg-induced CNS impairment. This study aims to investigate the expressions of IL-6, MIP-2, and MCP-5, as biomarkers in relation with MeHg-induced CNS impairment and N-acetyl-L-cysteine (NAC) treatment in mice, as well as histopathological changes of brain tissue and clinical symptom such as ataxia. Twenty male Balb/c mice, aged 8-9 weeks, were divided into 4 groups and treated with saline (control), NAC [150 mg/kg body weight (BW) day], MeHg (4 mg Hg/kg BW), or a combination of MeHg and NAC for 17 days. MeHg induced the expression of IL-6, MIP-2, and MCP-5 in the serum, with median values (those in controls) of 55.06 (9.44), 15.94 (9.30), and 458.91 (239.91) mg/dl, respectively, and a statistical significance was observed only in IL-6 expression (p < 0.05). MIP-2 and MCP-5 expressions tended to increase in the cerebrum of MeHg-treated group compared with controls; however, the difference was not statistically significant. MeHg treatment also increased IL-6 expression in the cerebellum (7.73 and 4.81 mg/dl in MeHg-treated group and controls, respectively), with a marginal significance. NAC significantly suppressed MeHg-induced IL-6 and MIP-2 expressions in the serum (p < 0.05 for both), and slightly reduced MCP-5 expression in the cerebrum. Ataxia was observed in all MeHg-treated mice after 9-day exposure as well as the decrease of intact Purkinje cells in brain tissue (p < 0.05). These findings suggest that MeHg induced neurotoxicity by elevating the expression of IL-6, MIP-2, and MCP-5 and causing ataxia symptoms, and NAC reduced MeHg-mediated effects on the CNS.

Citation

Muflihatul Muniroh, Ainun Rahmasari Gumay, Darmawati Ayu Indraswari, Yuriz Bahtiar, Hardian Hardian, Saekhol Bakri, Nani Maharani, Vega Karlowee, Chihaya Koriyama, Megumi Yamamoto. Activation of MIP-2 and MCP-5 Expression in Methylmercury-Exposed Mice and Their Suppression by N-Acetyl-L-Cysteine. Neurotoxicity research. 2020 Apr;37(4):827-834