大蒜素通过下调肉鸡空肠 P-糖蛋白和乳腺癌耐药蛋白的表达来影响磺胺嘧啶和氟苯尼考的药代动力学。
Allicin affects the pharmacokinetics of sulfadiazine and florfenicol by downregulating the expression of jejunum P-gp and BCRP in broilers.
机构信息
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang, Nanjing 210095, China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Weigang, Nanjing 210095, China; Jiangsu Key Laboratory of Sericutural Biology and Biotechnology, School of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212018, China.
出版信息
Poult Sci. 2022 Jul;101(7):101947. doi: 10.1016/j.psj.2022.101947. Epub 2022 May 5.
Allicin, one of the main bioactive compounds in garlic, is an excellent feed additive. It is unknown whether allicin affects the expression of P-gp and BCRP, 2 important ABC efflux transporters related to the pharmacokinetics of antimicrobials in chickens. In this study, by bidirectional transport test and broiler jejunum in situ perfusion, we found that allicin inhibited the efflux transport of P-gp and BCRP for their substrates sulfadiazine and florfenicol, 2 commonly used antimicrobials in broilers. Furthermore, we observed that allicin decreased the mRNA expression of chicken jejunum P-gp and BCRP. Pretreatment with allicin changed the pharmacokinetic behavior of orally administered sulfadiazine, by increasing AUC (41.85 vs. 31.24, P < 0.01) and C values (9.82 vs. 8.40, P < 0.05) and decreasing CL (0.45 vs. 0.62, P < 0.01). Similarly, pretreatment with allicin also altered pharmacokinetics of orally administered florfenicol, by increasing AUC (18.38 vs. 13.52, P < 0.01) and decreasing CL. The results indicate that allicin could inhibit jejunum P-gp and BCRP expression and efflux function, thereby increasing the plasma concentrations of their substrates in broilers.
大蒜中的主要生物活性化合物之一——大蒜素，是一种极好的饲料添加剂。目前尚不清楚大蒜素是否会影响与禽用抗菌药物药代动力学相关的 2 种重要 ABC 外排转运蛋白 P-糖蛋白（P-gp）和乳腺癌耐药蛋白（BCRP）的表达。在这项研究中，我们通过双向转运试验和肉鸡空肠原位灌流试验发现，大蒜素抑制了磺胺嘧啶和氟苯尼考这 2 种肉鸡常用抗菌药物的底物 P-gp 和 BCRP 的外排转运。此外，我们观察到大蒜素降低了肉鸡空肠 P-gp 和 BCRP 的 mRNA 表达。大蒜素预处理改变了口服磺胺嘧啶的药代动力学行为，增加了 AUC（41.85 比 31.24，P<0.01）和 C 值（9.82 比 8.40，P<0.05），降低了 CL（0.45 比 0.62，P<0.01）。类似地，大蒜素预处理也改变了口服氟苯尼考的药代动力学，增加了 AUC（18.38 比 13.52，P<0.01）和降低了 CL。结果表明，大蒜素可以抑制空肠 P-gp 和 BCRP 的表达和外排功能，从而增加肉鸡中这些底物的血浆浓度。
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