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新西兰白兔中二丙烯基腈衍生的两种腈类化合物的肝毒性。

Hepatotoxicity of Two Progoitrin-Derived Nitriles in New Zealand White Rabbits.

机构信息

School of Veterinary Science, Massey University, Private Bag 11-222, Palmerston North 4442, New Zealand.

出版信息

Toxins (Basel). 2020 Nov 2;12(11):695. doi: 10.3390/toxins12110695.

Abstract

Cattle occasionally develop brassica-associated liver disease (BALD) and photosensitisation when grazing turnip or swede ( spp.) forage crops. The liver toxin in these brassica varieties has yet to be discovered. Progoitrin is the dominant glucosinolate in incriminated crops. Apart from goitrin, progoitrin hydrolysis yields the nitrile, 1-cyano-2-hydroxy-3-butene (CHB), and the epithionitrile, 1-cyano-2-hydroxy-3,4-epithiobutane (CHEB). The two compounds were custom-synthesised. In a small pilot trial, New Zealand White rabbits were given either CHB or CHEB by gavage. Single doses of 0.75 mmol/kg of CHB or 0.25 mmol/kg of CHEB were subtoxic and elicited subclinical effects. Higher doses were severely hepatotoxic, causing periportal to massive hepatic necrosis associated with markedly elevated serum liver biomarkers often resulting in severe illness or death within 24 h. The possibility that one or both of these hepatotoxic nitriles causes BALD in cattle requires further investigation.

摘要

牛在放牧萝卜或大头菜( spp.)饲料作物时偶尔会发生 Brassica 相关肝疾病 (BALD) 和光过敏。这些 Brassica 品种中的肝毒素尚未被发现。前体硫代葡萄糖苷是受牵连作物中的主要硫代葡萄糖苷。除了 goitrin 外,前体硫代葡萄糖苷水解生成腈,1-氰基-2-羟基-3-丁烯 (CHB) 和亚乙基硫代氰酸酯,1-氰基-2-羟基-3,4-亚乙基硫代丁烷 (CHEB)。这两种化合物是定制合成的。在一项小型试点试验中,新西兰白兔通过灌胃给予 CHB 或 CHEB。0.75 mmol/kg 的 CHB 或 0.25 mmol/kg 的 CHEB 的单剂量是亚毒性的,并引起亚临床效应。更高的剂量具有严重的肝毒性,导致门脉周围至大量肝坏死,与明显升高的血清肝生物标志物相关,通常在 24 小时内导致严重疾病或死亡。这些肝毒性腈中的一种或两种是否会导致牛的 BALD 需要进一步调查。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb2c/7693095/6311349527ba/toxins-12-00695-g001.jpg

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