| Acetaminophen(APAP)is a medicine which is widely used to remove fever and relieve pain.Because of the influence of the experimental animals,only it`s liver toxicity was known,while little has been known to its other side effects.To better study the toxicity of acetaminophen,zebrafish was administrated with the medicine by three different ways in the study.To ascertain sustained toxicity of acetaminophen in zebrafish embryo,4hpf zebrafish embryos were administrated with acetaminophen of three different concentrations(2mmol/L,4mmol/L and 8mmol/L)for 96 h.Then hatching rate,survival rate,pericardium area and pigmentation were observed at72 h and 96 h post treatment.The results showed that hatching rate and survival rate were both reduced during the embryo incubation.Besides,tail curve,pigmentation reduction and heart pouch dropsy was also found in tested zebrafish.Then further study was carried out by fluorescence quantitative PCR,and the expression of TRH,DIO2,DIO3 and THRβ were different from the control group.The expression of fatty acid binding protein genes FABP10,silk crack factor activated protein kinase P38 A,and apoptosis promoting gene BAX and apoptosis inhibiting gene MCL-1B were all affected by acetaminophen,which indicated that the expression of some genes of zebrafish embryos were affected by continuous action of acetaminophen.For the research of acetaminophen toxicity of short time action in zebrafish embryo,different concentrations of acetaminophen were used to treat 4hpf zebrafish embryos.then acetaminophen was washed off from the zebrafish24 h post exposure and zebrafish nutrient solution was put in.The results similar to the former test was gotten.All the above indicated that short-term action or continuous action of acetaminophen can destroy pigment cells,affect the secretion of thyroxine and promote the apoptosis of liver cells of zebrafish.Further study of acetaminophen toxicity to 3-day-old zebrafish also confirmed the toxicity of acetaminophen.Lastley,transcriptome sequencing of zebrafish in acetaminophen treated group and control group was carried out.Based on the transcriptome data from the samples of the 2groups,15198 new genes were predicted,among which there were 350905 new variants,and 12303 gene structures were optimized.Meanwhile,the differentially expressed genes in each sample were analyzed.The results showed that there were 72 differentially expressed genes in the CO group and the CAPAP group.Among the 72 genes,40 of them were up-regulated and 32 were down regulated.Compared with the control group,the significantly up-regulated genes in treatment group were BX323060.3,zgc:109934,prdx1(peroxiredoxin 1),ndst1a[N-deacetylase/N-sulfotransferase(heparan glucosaminyl)1a],gstp1(glutathione S-transferase pi 1),rnf150b(ring finger protein150b),fkbp5(FK506 binding protein 5),and so on.Among them,the genes related to liver damage mainly were prdx1,gstp1,fkbp5,txn,ucp3,tm4sf4,mt-cyb,ddx5,g3bp2,anxa4 and try.Compared with the control group,significantly down regulated genes mainly were ndrg1b(N-myc downstream regulated 1b,),SLC38A9(solute carrier family 38 member 9),ela3l(elastase 3 like),prss59.2(protease,serine,59,tandem duplicate2),opn1mw1(opsin 1 cone pigments medium-wave-sensitive 1),g3bp2(G3BP stress granule assembly factor 2),ctsbb(cathepsin B)and so on.Among the genes,Rho,opn1lw2 and opn1mw1 were associated with pigmentation. |
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