The effects of subcutaneous administration of T-2 toxin on liver drug metabolizing enzymes in piglets
The effects of subcutaneous administration of T-2 toxin on liver drug metabolizing enzymes in piglets
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DOI：
10.1080/02772240701550182
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发表时间：
2008-01-01
影响因子：
1.8
通讯作者：
Kumagai, Susumu
中科院分区：
文献类型：
--
作者：
Dong, Kesu;Sugita-Konishi, Yoshiko;Kumagai, Susumu
T-2 毒素是单端孢霉烯族毒素之一，单端孢霉烯族毒素是由镰刀菌属和相关真菌物种产生的一组结构多样的有毒次生代谢产物。这种毒素通常会污染世界各地的谷物。尽管猪越来越多地被用于药理学和毒理学研究，但关于 T-2 毒素对猪药物代谢酶的影响还没有足够的信息。本研究的目的是探讨皮下注射T-2毒素对仔猪肝脏I相和II相代谢酶活性的影响。通过单次皮下 (s.c.) 注射，向仔猪施用溶解在 DMSO 中的 0.3 mg T-2 毒素/Kg BW。对照动物仅接受媒介物(DMSO)。在最后一次皮下注射后 24 小时和 48 小时测定第一相和第二相酶的活性。注射。细胞色素P-450（CYP）1A2和2E1的活性在24和48小时时略有增加（P < 0.05）。 CYP3A4活性在24 h时呈上升趋势（P < 0.01），48 h时呈下降趋势，但不显着（P > 0.05）。谷胱甘肽S-转移酶（GST）对氢过氧化异丙苯的活性在24 h时略有增加（P < 0.05），但在48 h时略有下降（P < 0.05）。在 24 小时或 48 小时，谷胱甘肽 S-转移酶对 1-氯-2,4-二硝基苯 (CDNB) 的活性没有观察到显着变化。肝脏组分的蛋白质印迹分析显示，24 小时时 CYP1A2、2E1、3A4、GST α、GST M1-1 水平升高，48 小时时 CYP2E1 水平升高。结果表明，T-2 毒素导致仔猪 I 期和 II 期药物代谢酶的调节。
T-2 toxin is one of trichothecenes, which are a structurally diverse group of toxic secondary metabolites produced by Fusarium and related species of fungi. The toxin usually contaminates cereal grains throughout the world. Although the pig is increasingly being used in pharmacological and toxicological studies, there is not enough information about the effects of T-2 toxin on drug-metabolizing enzymes in pigs. The purpose of this study is to investigate the effects of subcutaneous administration of T-2 toxin on the activities of hepatic Phase I and Phase II metabolizing enzymes in piglet liver. Piglets were administrated 0.3 mg T-2 toxin/Kg BW dissolved in DMSO by single subcutaneous (s.c.) injection. Control animals received only vehicle (DMSO). The activities of Phase I and Phase II enzymes were determined at 24 and 48 h after the last s.c. injection. The activities of cytochrome P-450 (CYP) 1A2 and 2E1 increased slightly at 24 and 48 h (P < 0.05). The CYP3A4 activity increased at 24 (P < 0.01), and tended to decrease at 48 h, but not significantly (P > 0.05). The glutathione S-transferase (GST) activity towards cumene hydroperoxide increased slightly at 24 h (P < 0.05), but decreased slightly at 48 h (P < 0.05). No significant changes were observed in the glutathione S-transferase activity toward 1-Chloro-2,4-dinitrobenzene (CDNB) either at 24 or 48 h. Western blot analyses of the liver fractions revealed increased levels of CYP1A2, 2E1, 3A4, GST alpha, GST M1-1 at 24 h, and that of CYP2E1 at 48 h.The results suggest that T-2 toxin causes modulation of Phase I and Phase II drug metabolizing enzymes in piglets.