| The Macleaya Cordata Extracts（MCE）is extracted from[Macleaya cordata（Willd）R.Br.],which is the main active component of the traditional Chinese veterinary medicine"Boluohui powder",which consists of Sanguinarine（SA）and Chelerythrine（CHE）.The MCE has good effects on bactericidal,anti-inflammatory and growth-promoting for animals.In order to guide its clinical application and ensure the safety of animal food,its pharmacokinetics,residue and eliminate,and the effect on metabolic enzymes（NQOs）.Based on the detection methods of SA and CHE had established by liquid-mass spectrometry in our laboratory,we administered low-dose(1.25 mg·kg-1),high-dose(12.5mg·kg-1)MCE extracts to female and male rats for 28 days.The basic diet with MCE at clinical recommended dose(1.875mg·kg-1)or 5 times clinical recommended dose(9.375mg·kg-1)was fed to female,male yellow-feathered broiler chickens for 28 days,and pig for 90 days.SA and CHE pharmacokinetics studies in different sex rats were carried.The SA and CHE residues in heart,liver,spleen,lung,kidney,muscle tissue and cecum contents of rats,chickens,pigs were detected at second hour,twelfth hour,first,third,and fifth day after withdrawal of MCE.And the gene expression of metabolic enzyme NQOs was also detected.The pharmacokinetic parameters of SA and CHE in high-dose group rats indicate that the maximum blood concentration of SA in female rats is 33.12±5.08μg·L-1,w hich is larger than that of male rats(24.36±5.46μg·L-1).The AUC（0-）∞</sub>of female rats is 102.95±24.52(μg·L-1)·h,which is larger than that of male rats(76.60±15.90(μg·L-1)·h).The t1/2 of female rats is 1.38±0.16 h,which is smaller than that of male rats（2.02±0.46 h）.The peak time of SA is 2.17±0.29 h in female and male rats.The maximum blood concentration of CHE in female rats is 5.74±0.42μg·L-1,which is larger than that of male rats(4.25±0.66μg·L-1).The AUC（0-∞）of female rats is16.21±3.60(μg·L-1)·h,which is larger than that of male rats(13.44±3.41(μg·L-1)·h).The t1/2of female rats is 1.30±0.21 h,which is smaller than that of male rats（1.99±0.18 h）.The peak time of CHE is 1.67±0.29 h in female and male rats.Pharmacokinetic parameters of SA and CHE in low dose group show no significant difference between male and female.After withdrawal of MCE for 3 days,there was no SA or CHE was detected in rat organs,muscles and cecum contents.CHE was not detected in organs and muscles after 1day of withdrawal.SA and CHE remained mainly in the liver,lung and kidney.The residue in male rats was higher than that in female rats.After withdrawal of MCE for 3 days,no SA and CHE was detected in the cecu m contents of yellow-feathered broiler chickens or pigs.After withdrawal for 2 hours in recommended dose group,and 12 hours in 5 times recommended dose group,SA and CHE were not detected in organs and muscles.SA mainly remained in liver,lu ng and kidney,while CHE remained in the heart and lungs.Similarly,the levels of r esidue in female group were higher than that in male group.After continuous administration of MCE,the gene expression of NQO1 in the li ver and kidney of rats,yellow-feathered broiler chickens and pigs increased,while th e gene expression of NQO2 decreased.The expression of NQO1 in rat,pig kidn ey was higher than that in liver,but in chicken kidney,it was lower than that in liver.The results of this paper showed that after long-term administration of high dose SA and CHE,there were residues in rats,but they were eliminated fastly and woul d not accumulate in vivo.Sex differences in metabolism of SA and CHE in rats and yellow-feathered broiler chickens were found.After long-term feeding of chickens an d pigs at recommended doses of SA and CHE,they were eliminated from organs an d muscle rapidly（≤2h）,and no accumulation appeared.The metabolic enzymes invo lved in SA and CHE in rats,yellow-feathered broiler chickens and pigs may be dom inated by NQO1 and there was species differences.All in all,it provided theoretical guidance and technical support for the clinical use of Boluohui Powder in yellow-feat hered broiler chickens and pigs,and enriched its safety evaluation research. |
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