Toxic effects of Fusarium mycotoxin butenolide on rat myocardium and primary culture of cardiac myocytes.
Mycotoxin toxicosis has been implicated in the etiopathogenesis of Keshan disease (KD), an endemic cardiomyopathy prevailing in some regions of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone, CAS No. 16275-44-8), a mycotoxin produced by several Fusarium species such as Fusarium tricinctum and Fusarium graminearum, is frequently detected from the cereals in the endemic areas of KD. The present study is undertaken to investigate whether this mycotoxin can induce myocardial damage. Exposure of primary culture of cardiac myocytes to butenolide resulted in significant cytotoxicity, manifested by changes in cell morphology and decreases in cell viability. Consistent with the in vitro findings, distinct myocardial toxicity in vivo was observed after administration of rats by gavage with butenolide (10 and 20 mg/kg/day) for 2 months, and the myocardial injuries were characterized by focal necrosis of myocardium and fragmentation of myofiber. Butenolide also induced significant oxidative damage to the myocardium in vitro evidenced by a concentration-dependent lipid peroxidation in the myocardial homogenates, whereas antioxidants superoxide dismutase (SOD), N-acetylcysteine (NAC) and glutathione (GSH) provided significant protections against this oxidative effect. Taken together, these results clearly reveal that butenolide possesses the potential to induce myocardial toxicity. The present findings may reinforce the hypothesis that toxicosis by mycotoxins is one of the etiological factors for KD.
Liu
Jing-Bo
JB
Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Haidian District, Beijing 100850, PR China.
Wang
Yi-Mei
YM
Peng
Shuang-Qing
SQ
Han
Gang
G
Dong
Yan-Sheng
YS
Yang
Hai-Ying
HY
Yan
Chang-Hui
CH
Wang
Guo-Qiang
GQ
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005670:Fusarium / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D015227:Lipid Peroxidation; D015394:Molecular Structure; D009183:Mycotoxins / Q000737:chemistry / Q000633:toxicity; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D009183:Mycotoxins; C004511:butenolide; D015107:4-Butyrolactone