Effects of Fusarium mycotoxin butenolide on myocardial mitochondria in vitro

Toxicol Mech Methods. 2009 Feb;19(2):79-85. doi: 10.1080/15376510802322802.


Fusarium mycotoxin toxicosis has been implicated in the etiology of Keshan disease, an endemic mitochondrial cardiomyopathy prevailing in certain areas of China. Butenolide (4-acetamido-4-hydroxy-2-butenoic acid gamma-lactone) is one of the Fusarium mycotoxins which are frequently detected from cereal grains in endemic areas. A recent study indicates that this mycotoxin induces rat cardiotoxicity, but its effect on the myocardial mitochondria remains unclear. The present study is therefore undertaken to explore the toxic effect potential of butenolide on the myocardial mitochondria. Exposure of cultured cardiac myocytes to 50 microg/ml of butenolide provoked dissipation of mitochondrial membrane potential. Incubation of isolated rat myocardial mitochondria with butenolide of 100 microg/ml for 60 min resulted in mitochondrial swelling, indicating the occurrence of mitochondrial permeability transition. Furthermore, marked oxidative damage in myocardial mitochondria was observed after incubation of isolated myocardial mitochondria with butenolide ranging from 0 to 50 microg/ml for 60 min, as manifested by concentration-dependent increases in the production of thiobarbituric acid reactive substances, the indicator of lipid peroxidation. Contrarily, a representative antioxidant glutathione significantly alleviated this oxidative mitochondrial damage induced by butenolide. In conclusion, these observations clearly show that butenolide can induce dysfunction of myocardial mitochondria, and oxidative damage appears to play a crucial role in these deleterious effects. The present study supports the hypothesis that mycotoxin toxicosis is a probable etiological factor of Keshan disease, the mitochondrial cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Animals
  • Cells, Cultured
  • Fusarium / metabolism*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Lipid Peroxidation / drug effects
  • Membrane Potential, Mitochondrial / physiology
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism
  • Molecular Structure
  • Mycotoxicosis / etiology
  • Mycotoxicosis / physiopathology
  • Mycotoxins / pharmacology*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Rats
  • Rats, Wistar


  • Immunosuppressive Agents
  • Mycotoxins
  • butenolide
  • 4-Butyrolactone