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豚鼠体内3H标记的T-2霉菌毒素的归宿与分布

Fate and distribution of 3H-labeled T-2 mycotoxin in guinea pigs.

作者信息

Pace J G, Watts M R, Burrows E P, Dinterman R E, Matson C, Hauer E C, Wannemacher R W

出版信息

Toxicol Appl Pharmacol. 1985 Sep 30;80(3):377-85. doi: 10.1016/0041-008x(85)90382-5.

Abstract

T-2 toxin is a potent cytotoxic metabolite produced by the Fusarium species. The fate and distribution of 3H-labeled T-2 toxin were examined in male guinea pigs. Radioactivity was detected in all body tissues within 30 min after an im injection of an LD50 dose (1.04 mg/kg) of T-2 toxin. The plasma concentration of trichothecene molar equivalents versus time was multiphasic, with an initial absorption half-life equal to or less than 30 min. Bile contained a large amount of radioactivity which was identified as HT-2, 4-deacetylneosolaniol, 3'-hydroxy HT-2, 3'-hydroxy T-2 triol, and several more-polar unknowns. These T-2 metabolites are excreted from liver via bile into the intestine. Within 5 days, 75% of the total radioactivity was excreted in urine and feces at a ratio of 4 to 1. The appearance of radioactivity in the excreta was biphasic. Metabolic derivatives of T-2 excreted in urine were T-2 tetraol, 4-deacetylneosolaniol, 3'-hydroxy HT-2, and several unknowns. These studies showed a rapid appearance in and subsequent loss of radioactivity from tissues and body fluids. Only 0.01% of the total administered radioactivity was still detectable in tissues at 28 days. The distribution patterns and excretion rates suggest that liver and kidney are the principal organs of detoxication and excretion of T-2 toxin and its metabolites.

摘要

T-2毒素是镰刀菌属产生的一种强效细胞毒性代谢产物。对雄性豚鼠体内3H标记的T-2毒素的归宿和分布进行了研究。腹腔注射半数致死剂量(1.04毫克/千克)的T-2毒素后30分钟内,在所有身体组织中均检测到放射性。血浆中单端孢霉烯摩尔当量浓度随时间呈多相变化,初始吸收半衰期等于或小于30分钟。胆汁中含有大量放射性物质,经鉴定为HT-2、4-脱乙酰新茄病醇、3'-羟基HT-2、3'-羟基T-2三醇以及几种极性更强的未知物。这些T-2代谢产物从肝脏经胆汁排泄到肠道。5天内,75%的总放射性以4比1的比例经尿液和粪便排出。排泄物中放射性的出现呈双相。尿液中排泄的T-2代谢衍生物为T-2四醇、4-脱乙酰新茄病醇、3'-羟基HT-2以及几种未知物。这些研究表明,放射性物质在组织和体液中迅速出现并随后消失。在28天时,组织中仍可检测到的放射性仅占总给药放射性的0.01%。分布模式和排泄速率表明,肝脏和肾脏是T-2毒素及其代谢产物解毒和排泄的主要器官。

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