| Antibiotics are largely used in animal husbandry and aquaculture industries.Sulfonamides are frequently used and have high detection rate in the environment which present a persistent and low-dose condition.At present,the laboratory exposure of antibiotics to freshwater fish is mainly focus on the aqueous experiment to explore the bioaccumulation,metabolism,ecotoxicological effects,and lack the dietary exposure to marine fish,however,fish ingest medicine mostly by diet in the aquaculture.In this study,sulfamethazine(SM2)and its acetylated metabolite,sulfamethazine-N4acetyl(N-SM2),were used as target compounds.Oryzias melastigma(Marine medaka)and Artemia salina were used as model organism.SM2 was transfer by food chain and marine medaka went through 28 days dietary exposure(20 ?g/L,200 ?g/L)to research the bioaccumulation and metabolic transformation regular pattern,difference between gender and tissue simultaneously.Combined with protemics,we explore the toxicity mechanism of SM2 to growth and metabolism in the marine medaka.The bioaccumulation and distribution of SM2 and N-SM2 in various tissues of the marine medaka under the dietary exposure condition revealed in this study can provide scientific reference for antibiotic detection and reasonable consumption of marine fish.The study found:(1)The bioaccumulation level of SM2 in Artemia salina by aqueous exposure has increased with increasing concentration(20 ?g/L,200?g/L,2000 ?g/L)and has significant difference.The bioconcentration level are 10.3 3±2.57 ng/g,61.86±2.36 ng/g,704.76±11.25 ng/g in different concentration group respectively.N-SM2 can be detected at a low concentration in the larva of the Artemia salina,indicating that they have metabolic activity on SM2 during the hatching process or larval stage.(2)After SM2 dietary exposure to marine medaka,SM2 and N-SM2 can be detected in the bile,liver,gonad,gills,and muscle tissues in the marine medaka,and the main accumulated organ is the gallbladder.Under different exposure time,the peak concentration of SM2 enrichment was in the early stage of exposure,and the bioaccumulation level of each tissue increased first,then decreased and reached the absorption-metabolism balance.The peak concentration of N-SM2 enrichment was in the middle of exposure,and through the exposure time,the proportion of N-SM2 is increased.SM2 is metabolized by liver tissue to N-SM2 and discharged to the water environment through enterohepatic circulation.During the withdrawal time,the concentration of SM2 and N-SM2 could be detected in various tissues decreased,but they still could be detected in the end stage of withdrawal time,indicating that it has a certain bioaccumulation effect and a long half-life in marine medaka.During the dietary exposure,there was no significant difference in the levels of SM2 bioconcentration in the different concentration groups,while the metabolite N-SM2 had a high bioconcentration level in the high concentration group.Between different genders,there was no significant difference in the bioconcentration levels of SM2 and N-SM2.(3)After SM2 dietary exposure to marine medaka,liver proteomic analysis revealed that signal pathway expression,energy metabolism,amino acid metabolism,and drug metabolism-related proteins were up-regulated during SM2 dietary exposure.The energy generated during the energy metabolism process was used to biotransform SM2 and excrete the parent and its metabolite N-SM2.During the dietary exposure,the expression of the pathways related to cell growth was down-regulated,SM2 exposure can inhibit cell growth and development,and cause damage to tissues and liver cells to some extent.gonadotropin secretion is inhibited,which interferes with the reproduction capacity of marine medaka.Male medaka proteome expression was mainly upregulated,and its growth and metabolism were promoted,while female medaka proteome expression is reversed. |
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