Tizoxanide mitigates inflammatory response in LPS-induced neuroinflammation in microglia via restraining p38/MAPK pathway

X.-W. Li, R.-Z. He, Y. Li, Z.-F. Ruan

Department of Neurology, The First Affiliated Hospital of University of South China, Hengyang, China. ruanzhongfan@sina.com

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• Pharmacology

OBJECTIVE: Traumatic brain injury (TBI) induced neuroinflammation is featured as excessive glial inflammatory activation and violent neurologic destruction and dysfunction. Massive microglia activation in situ and disrupt of blood-brain barrier contribute to severely collapsed nervous system. Tizoxanide (TIZ), a synthetic thiazolide derivative agent possessing a broad-spectrum anti-infective effect, currently shows a potential resistance against pathogens like bacteria, virus and parasites, while its underlying role in neuroinflammation is elusive. The study aimed to explore the effect of TIZ on neuroinflammation in vitro microglia.

MATERIALS AND METHODS: Primary microglia were accepted to neuroinflammatory activation via lipopolysaccharide (LPS) administration. TIZ was conducted to pretreatment of microglia. Cell viability, inflammatory cytokines, chemotaxis, nitric oxide release, inflammation-related enzymes, and mitogen-activated protein kinase (MAPK) pathway activation in microglia were investigated respectively.

RESULTS: We demonstrated that TIZ administration attenuates inflammatory cytokines and chemokines through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) of medium supernatant. In addition, TIZ reduces pro-inflammatory mediators and nitric oxide release in microglia. Furtherly, TIZ inhibits the level of p38/MAPK pathway in LPS stimuli, indicating that TIZ negatively regulates neuroinflammation via inhibiting p38/MAPK pathway.

CONCLUSIONS: TIZ is verified to be an anti-inflammation effect on neuroinflammation in microglia via downregulation of p38/MAPK pathway, which restrains inflammation by reduced inflammatory cytokines, chemokines and mediators and decreased nitric oxide release. To summarize, TIZ is considered to be a promising reagent to alleviate neuroinflammation targeting microglia in nervous system injury.

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