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Simvastatin attenuates delayed encephalopathy induced by carbon monoxide poisoning in rats by regulating oxidative stress, inflammation and NF-κB pathway
Molecular & Cellular Toxicology  (IF1.08),  Pub Date : 2021-02-22, DOI: 10.1007/s13273-021-00124-x
Zhe Chu, Zuolong Liu, Wei Li, Dahai Xu, Li Pang

Background

Carbon monoxide (CO) poisoning is a leading cause of morbidity and mortality worldwide. The delayed encephalopathy occurs a period after poisoning in patients without effective treatment. Simvastatin (Sim), a lipid-lowering drug, was reported to exert endothelial protective effects and inhibit inflammatory response. This research focused on the effects of Sim on delayed encephalopathy caused by CO poisoning.

Objective

The acute CO poisoning model was established by exposing rats to 2500 ppm CO gas for 40 min, then 3000 ppm for 30 min or until they lost consciousness. Rats in the treatment group were given Sim (20 mg/kg/day, ig.). The behavioral tests included the Morris water maze test and shuttle box. The pathological changes were evaluated by H and E staining. The inflammatory mediators were analyzed by ELISA. The expression levels of eNOS, iNOS and the NF-κB-related proteins were analyzed by Western blot.

Results

The results showed that Sim could alleviate CO-induced behavioral disorders and the hippocampal nerve cells apoptosis. Sim administration reversed the effects of CO on oxidative stress-related molecules. Sim could also inhibit the production of the inflammatory mediators induced by CO. The level of eNOS was decreased after CO exposure, while iNOS was increased. Sim could significantly inhibit the effects of CO. Furthermore, Sim inhibited the phosphorylation of IκBα (an NF-κB inhibitory protein), i.e., the activation of NF-κB, which indicated that Simvastatin reduced the inflammatory response induced by CO poisoning partially through inhibiting the activation of NF-κB signaling pathway.

Conclusion

To sum up, our research indicated that Sim could attenuate the delayed encephalopathy induced by CO poisoning via regulating oxidative stress, inflammation and NF-κB pathway.