The Hepatotoxicity And Mechanism Of[C₁₄mim]Br

Background:Ionic liquids?ILs?are organic salts with a low melting point that are comprised of various cations such as imidazolium,pyridinium,piperidinium,ammonium,and pyrrolidinium,of which imidazolium is the most widely used,and anions such as chloride?Cl^-?,bromide?Br^-?,tetrafluoroborate?BF₄^-?,and hexafluorophosphate?PF₆^-?.Owing to their excellent physicochemical properties,such as low vapor pressure,nonflammability,thermal and chemical stability,excellent solvation ability,ILs have been regarded as“environmental compatible”and“green”substitutes for conventional industrial volatile organic chemicals.With the excellent properties,ILs have been used in various applications,involving electrochemistry,textiles,the food industry,the medical field,ecology,and chemical engineering.However,ILs reduce the risk of air pollution due to insignificant vapor pressure,they have significant water solubility and poor biodegradability;therefore,they may be released into aquatic ecosystems and terrestrial ecological systems by effluents or accidental spills and many thus become a new threat to aquatic and terrestrial organisms.Most research has focused on ILs in organisms,enzymes,cells,and plants.The rats has been used as a bio-indicator for chemical toxicity experiments by the Organisation for Economic Co-operation and Development?OECD?,and rats has been widely used in acute toxicity and chronic toxicity experiments.But few researches were studied the toxicity of ILs to rats.Aim:In order to study the hepatotoxicity of bromide 1-tetradecyl-3-methyl imidazole salt([C₁₄mim]Br)on treated rat liver and effect of antioxidant system,evaluate its possible Nrf2 pathway molecular mechanism.Methods:Three different dosage groups?2.5 mg/kg,5 mg/kg,10mg/kg?and one blank control group were set up.After rat were treated with[C₁₄mim]Br solution by intragastric administration for 90 days,the effects of[C₁₄mim]Br on weight,serum biochemical index,histomorphology in rats liver were observed.Then lipid peroxide,antioxidant enzymes,anti-oxidation capacity were evaluated.Finally,we can calculate expressions of Nrf2-Keap1 pathway protein such as Nrf2,Keap1,HO-1,NQO1 was analyzed by using Western blot.Results:Compared with the blank control group,there showed a decreasing trend of body weight increase in[C₁₄mim]Br groups.And this effect showed in a dose-dependent manner.The ratio of liver to body?the coefficients of liver?was positively related with the[C₁₄mim]Br dosages.The serum levels of ALP,ALT,AST,DBIL and GLB were significantly increased,while A/G,TP values were significantly decreased.HE staining showed that the liver and kidney tissue in rats with different dosages of[C₁₄mim]Br administration were damaged in different degrees.The Nrf2protein levels decreased with the concentration but Keap1 protein levels increased.Especially,a remarkable decrease in HO-1?NQO1?SOD1?CAT protein levels was found exposed to the dose of 10 mg/kg.Conclusion:[C₁₄mim]Br can induce liver damage to rats and destroy its antioxidant defense system,leading to oxidative damage and lipid peroxidation.[C₁₄mim]Br contributes to rats liver injury by affecting the Nrf2-Keap1 signaling pathway.