Study On The Effects Of Ethanol And Kynurenic Acid On Tryptophan Metabolism And Other Pathway In Mouse

Excessive alcohol(ethanol)use has long been known to have a negative effect on human health,particularly in the central nervous system and immune system.Moreover,consumption of alcohol is often mixed with kynurenic acid(KA),an abundant tryptophan metabolite produced during fermentations.KA also widely presents in various foods and beverages such as tea,coffee,honey,etc.Therefore,it is inevitable for alcoholics to ingest alcohol and KA together.KA can be an antagonist at several subtypes of glutamate receptors,and able to protect nerve receptors from excessive activation and inhibit inflammation.It plays an important role in both the central nervous system and the immune system.The effects of alcohol have been discussed extensively,but the combined effects of ethanol and KA on host gene expression have not been investigated.The current study used mice as the model.Adult male mice were administered with2g/kg ethanol and/or 0.1mg/kg KA by gavage once a day for a week.Three organs: brain,kidney,and liver were collected.Fluorescence quantitative PCR and ELISA were used to detect the expression of various metabolic enzyme genes in tryptophan metabolism,and the protein concentrations of the tryptophan metabolic enzymes in different tissues,respectively.The expressions of other genes were also investigated through transcriptome sequencing to further study the effects of alcohol and/or KA on tryptophan metabolism and other physical function in transcriptional level.The results indicated that alcohol and KA co-administration increases tryptophan kynurenine metabolism.KA administration alone showed more genes showing transcriptional upregulation,while alcohol and KA co-administration had the strongest inhibitory effect in gene transcription.Furthermore,the co-administration of alcohol and KA can greatly enhance the Gn RH signaling pathway gene expression.In conclusion,we have reported that the effects of alcohol and/or KA on different organs and the interactional effects between alcohol and KA in gene expression,which provided new ideas and basic data for subsequent studies.Since the most of alcoholic beverages in the market contain KA,our findings may have implications for evaluation of the product safety for human health.