Toxicokinetic Study Of Zearalenone And Its Metabolites In SanHuang Chickens

Zearalenone(ZEA),known as F-2 toxin as well,produced by Fusarium,which is a estrongn-like mycotoxin that is toxic to humans and animals,it is widespreadly found in cereals and other feeds,it may cause immunodeficiency,liver toxicity and cytotoxicity,resulting in"high estrogen syndrome" and carcinogenicity,which will have a negligible impact on the livestock industry.Studies have shown that the main metabolites in the liver and small intestine after Zearalenone intake in animals is ?-Zearalenol(?-ZOL)and ?-Zearalenol(?-ZOL).Objective:There have been numerous reports on the detection of Zearalenone in grains,but few studies have been performed on animals,especially the Toxicokinetics of Zearalenone and its metabolites in blood.In this paper,we aimed at set up a rapid and simple multi-residues detection method to study the toxicokinetic of Zearalenone in SanHuang chickens to enrich the kinetic data of the metabolism of Zearalenone in SanHuang chickens.Methods:The simultaneous determination of ZEA,?-ZOL and ?-ZOL was established by high performance liquid chromatography.The plasma was extracted twice with ethyl acetate and dried by nitrogen flow.The mobile phase was recovered.Separation on an Agilent ZORBAX SB-Aq(4.6x250mm)column with acetonitrile/water(45/55,v/v)eluting at flow rate equal to 1 mL·min-1,equilibrated to 18 min,PAD detection wavelength ZEA and The ?-ZOL was 236 nm and the ?-ZOL was 238 nm,quantified with ZEA,?-ZOL,and ?-ZOL peak areas.Eighteen yellow chickens were randomly divided into two groups.One group consisted of 12 animals for oral(po)administration and one group of 6 animals for intravenous(iv)administration.All received a dose of 1.2 mg/kg of ZEA via wing vein fixation.Indwelling needles before dosing,5,10,15,20,30,50,70,100,140 min and 3,4,6,7,9,12,16,20,24,36 h after dosing Blood was collected at time and plasma was separated.The data on the change of three substances in the blood with time were analyzed and analyzed by pharmacokinetics software to obtain pharmacokinetics parameters.Result:This study investigated the Toxicokinetics of Zearalenone at a dose of 1.2 mg/kg BW in SanHuang chickens given intravenous(iv)and oral(po)doses.Optimize pretreatment and detection methods for Zearalenone and its metabolites in plasma.A simple and high-efficiency,HPLC detection method was established.The limit of detection for ZEA,?-ZOL and ?-ZOL were 1.60±0.86 ng/mL?1.28±0.64 ng/mL andl.11±0.73 ng/mL in plasma.The were 88.94%?92.08%?93.52%?98.50%?88.60%?94.67%?Kinetical 4.4 pharmacokinetics analysis software was used to analyze and the chamber model analysis showed that ZEA,?-ZOL,and ?-ZOL all met the two-compartment model after oral administration and intravenous injection of 1.2 mg/kg ZEA to Sanhuangji.The pharmacokinetics parameters showed that ZEA was metabolized to ?-ZOL and ?-ZOL within 10 min after oral administration,and the content of the two was similar.ZEA reached the maximum plasma concentration of 64.3215.49 ng/mL at 0.5 h,and the content was below the detection limit after 3 h;?-ZOL and ?-ZOL all showed the maximum plasma concentration around 0.8 h,and the total?-ZOL content was higher than ?-The ZOL was high and fell to undetectable levels after 6 h and 7 h,respectively.The T1/2? of ZEA was 0.201±0.465h,and it reached a Cmax of 62.757±10.121?g/mL at 0.452±0.034h.The T1/2? was 1.593±0.847h,and the AUC was 81.115±7.427 h·?g/mL.CL was 12.896±2.013 mL/h/kg,and its bioavailability was 48.32%.?-ZOL reached Cmax of 42.833±6.619ng/mL and CL of 10.419±7.004mL/h/kg at 0.754±0.016h.The ?-ZOL at 1.008±0.077h reached a Cmax of 22.917±4.729 ng/mL and a CL of 10.419±7.004 mL/h/kg.After intravenous administration,the contents of ZEA,?-ZOL and ?-ZOL decreased rapidly with time,ZEA was 2.3 h,and ?-ZOL and ?-ZOL could not be detected after the content was reduced to the detection limit after 4 h.The T1/2? of ZEA,?-ZOL,and ?-ZOL were 0.095±0.041h,0.162±0.134h,and 0.114±0.013h,respectively,and the T1/2? were 0.828±0.019 h,1.215±2.816 h,and 3.324±0.259 h,respectively.The CL was 9.729 2.030 mL/h/kg,10.1730.086 mL/h/kg,and 11.394±1.758 mL/h/kg,and the Vd was 10.571±8.125,14.796±0.598,and 66.502±26.357 L/kg.Conclusion:This study successfully established HPLC method for detection of Zearalenone,?-Zearalenol.?-Zearalenol in plasma simultaneously.After intaked by chicken orally,Zearalenone was absorbed quickly and metablited into ?-Zearalenol.?-Zearalenol quickly.The metablits have high tissue penetrability and have extensive distribution,and may residue in some tissues.