Altered tissue amino acid metabolism in acute T-2 toxicosis

Altered tissue amino acid metabolism in acute T-2 toxicosis
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DOI:
10.3181/00379727-210-43947
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发表时间:
1995-12-01
影响因子:
--
通讯作者:
Smith, TK
Smith, TK
中科院分区:
其他
文献类型:
--
作者:
Meloche, JL;Smith, TK

文献摘要

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T-2毒素是一种镰孢霉烯属真菌毒素,已显示其改变食用污染饮食的动物的脑神经化学和进食行为。进行实验以确定改变的组织氨基酸代谢在急性T-2中毒的病因学中的作用。在给药后4小时和8小时切除肌肉组织,并测定氨基酸浓度。在给药后4小时观察到肝脏增大伴游离小中性、大中性和碱性氨基酸的肝脏浓度降低。脑和肌肉氨基酸浓度在很大程度上对治疗无效,当酪氨酸和赖氨酸的血浆浓度以及碱性氨基酸的总和下降时,肝氨基酸浓度在给药后8小时恢复到对照水平,此时观察到氨基酸血症,这部分是由于大的中性氨基酸,特别是支链氨基酸的血浆浓度增加。进行随后的实验以确定T-2毒素对给药后4小时肝切片中C-14-亮氨酸摄取和掺入蛋白质的影响。(游离+蛋白结合)摄取亮氨酸主要是由于亮氨酸掺入新合成的肝蛋白减少,结论是,在急性T-2中毒中,肝脏氨基酸摄取减少先于氨基酸血症,尽管尚不清楚这可能如何影响脑神经化学和行为的后续变化。
T-2 toxin is a Fusarium trichothecene mycotoxin that has been shown to alter brain neurochemistry and eating behavior in animals eating contaminated diets, Experiments were conducted to determine the role of altered tissue amino acid metabolism in the etiology of acute T-2 toxicosis, Fasted weanling rats were orally dosed with 0 or 2.0 mg T-2 toxin/kg body weight, Blood, brain, liver, and muscle tissue were excised 4 and 8 hr after dosing, and amino acid concentrations were determined, Hepatic enlargement coupled with reduced liver concentrations of free small neutral, large neutral, and basic amino acids were seen 4 hr after dosing, Brain and muscle amino acid concentrations were largely refractory to treatment, while the plasma concentrations of tyrosine and lysine, and the sum of the basic amino acids fell, Hepatic amino acid concentrations returned to control levels 8 hr after dosing at which time aminoacidemia was seen, This was due partially to an increase in plasma concentrations of large neutral amino acids including particularly the branched-chain amino acids. A subsequent experiment was conducted to determine the effect of T-2 toxin on C-14-leucine uptake and incorporation into protein in liver slices 4 hr after dosing, Exposure to T-2 toxin reduced total (free + protein-bound) uptake of leucine due primarily to reduced incorporation of leucine into newly-synthesized hepatic protein, It was concluded that reduced amino acid uptake by liver preceded aminoacidemia in acute T-2 toxicosis, although it is not clear how this might influence subsequent changes in brain neurochemistry and behavior.