Basal expression of metallothionein suppresses butenolide-induced oxidative stress in liver homogenates in vitro.
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.
Yang
Hai-Ying
HY
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.
Wang
Yi-Mei
YM
Peng
Shuang-Qing
SQ
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism
D009569:Nitric Oxide; C004511:butenolide; D008668:Metallothionein; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D015107:4-Butyrolactone