The Hepatotoxicity And Mechanism Of 1-tetradecyl-3-methylimidazole Tetrafluoroborate On Rats

Aim:Imidazole ionic liquids（ILs）are widely used,but they are easy to accumulate in the environment and produce toxicity.Therefore,it is of great significance to study the toxicity and mechanism of ILs.In this paper,rats were taken as experimental objects,and the acute toxicity of imidazole ILs([C₁₄mim]BF₄)on rats was evaluated by oral exposure.On this basis,the effects of chronic exposure of[C₁₄mim]BF₄ on rat liver antioxidant system and inflammatory reaction were studied,and the molecular mechanism of its toxic effect was discussed.Methods:1)Acute toxicity:The"Up-and-down procedure"（UPD）of the Organization for Economic Cooperation and Development（OECD）was used to study the acute toxicity of[C₁₄mim]BF₄ to rats,and the HE staining method was used to observe its damage to the liver,kidney,stomach and other organs and tissues of rats.2)Subchronic toxicity:Three exposure groups(12.5,25,50 mg·kg^-1),one recovery group(50 mg·kg^-1)and one control group were set up in the experiment.After 90 days of oral exposure to rats,[C₁₄mim]BF₄ was first investigated.The effects of body weight,serum biochemical indicators,visceral body index and histomorphological changes;Secondly,the effects of[C₁₄mim]BF₄ on antioxidant enzyme activity,inflammatory cytokine level,ROS,T-AOC and MDA content in rat liver were measured.Finally,the effect of[C₁₄mim]BF₄ on the expression of Keap1/Nrf2 and NF-κB/NLRP3 signaling pathway related proteins was detected.Results:1)After acute exposure,[C₁₄mim]BF₄ damaged the liver and kidney of rats,and its median lethal dose(LD₅₀)was 249.8 mg·kg^-1.2)After subchronic exposure of[C₁₄mim]BF₄ to rats,the levels of serum ALT,AST,ALP,GLB,γ-GT,DBIL and TBIL increased,while the levels of serum ALB and ALB/GLB decreased.Further study found that[C₁₄mim]BF₄ exposure led to an increase in the levels of ROS and MDA in the liver of rats,and the expression of Nrf2 and its downstream related antioxidant proteins（HO-1,NQO1,CAT,SOD1）decreased.In addition,compared with the normal group,the expressions of NF-κB p65 and NLRP3 in the liver of the exposed group was up-regulated,the levels of IL-1β,IL-6 and TNF-αwere increased,and the levels of IL-10 and TGF-βwere decreased.After 30 days of cessation of exposure,the liver injury in the recovery group was relieved,and the above indexes were improved to varying degrees.Conclusion:1)The acute toxicity of[C₁₄mim]BF₄ in rats is moderate;2)Subchronic exposure of[C₁₄mim]BF₄ can destroy the antioxidant defense system of the rat liver,induce oxidative stress,and lead to oxidative damage and inflammatory reaction of the liver.Its toxic effect may be through inhibiting the Keap1/Nrf2 signaling pathway and activating the NF-κB/NLRP3 inflammatory corpuscle signaling pathway in the rat liver.