Yang Hai-Ying, Wang Yi-Mei, Peng Shuang-Qing
Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da Street, Fengtai District, Beijing 100071, PR China.
Toxicon. 2009 Feb;53(2):246-53. doi: 10.1016/j.toxicon.2008.11.008. Epub 2008 Dec 3.
Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone) is a Fusarium mycotoxin which is frequently detected in foodstuffs and feedstuffs for human and animal consumption. It can evoke a broad spectrum of toxicities, thus posing a potential health risk to both humans and animals. Previous study showed that this mycotoxin produced a significant oxidative stress, and several antioxidants abated this effect. Metallothionein (MT) has been proposed as a potent antioxidant, therefore, this study attempts to determine whether endogenous expression of MT protects against butenolide-induced hepatic oxidative stress by using an in vitro incubation system of liver homogenates prepared from MT-I/II null (MT-/-) mice, and the corresponding wild type (MT+/+) mice. The results showed that butenolide elicited significant oxidative stress in both MT-/- mice and MT+/+ mice; however, MT-/- mice were more sensitive than MT+/+ mice to butenolide-induced hepatic oxidative stress, as evidenced by more production of thiobarbituric acid reactive substances and nitric oxide, and by more severe reductions of glutathione, superoxide dismutase and glutathione peroxidase in the liver homogenates of MT-/- mice than those of MT+/+ mice. These findings implicated the antioxidant potency of basal expression of MT in suppression of the oxidative stress of butenolide.
丁烯内酯(4-乙酰氨基-4-羟基-2-丁烯酸γ-内酯)是一种镰刀菌霉菌毒素,在供人类和动物食用的食品及饲料中经常被检测到。它能引发广泛的毒性,从而对人类和动物都构成潜在的健康风险。先前的研究表明,这种霉菌毒素会产生显著的氧化应激,并且几种抗氧化剂能减轻这种影响。金属硫蛋白(MT)已被认为是一种有效的抗氧化剂,因此,本研究试图通过使用从MT-I/II基因敲除(MT-/-)小鼠以及相应的野生型(MT+/+)小鼠制备的肝脏匀浆体外孵育系统,来确定MT的内源性表达是否能抵御丁烯内酯诱导的肝脏氧化应激。结果显示,丁烯内酯在MT-/-小鼠和MT+/+小鼠中均引发了显著的氧化应激;然而,MT-/-小鼠比MT+/+小鼠对丁烯内酯诱导的肝脏氧化应激更敏感,这表现为MT-/-小鼠肝脏匀浆中硫代巴比妥酸反应性物质和一氧化氮的生成更多,以及谷胱甘肽、超氧化物歧化酶和谷胱甘肽过氧化物酶的减少比MT+/+小鼠肝脏匀浆中的更严重。这些发现表明MT基础表达的抗氧化能力在抑制丁烯内酯的氧化应激方面具有作用。