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.