The Study Of Toxicology Mechanism Of Butenolide To Myocardium

Butenolide (4-acetamido-4-hydroxy-2-butenoic acid γ-lactone, BUT) is a major component elaborated by Fusarium tricinctum NRRL 3246. Fusarium species are often found on corn, barley, oat, and wheat kernels and, as agents of major storage rots, may produce toxins that contaminate human and animal food. This fungus produces butenolid, a mycotoxin investigated as the possible cause of fescue foot, a condition occurring in cattle grazing on tall fescue grass. The animals receiving the smaller dosage developed petechial hemorrhages and acute inflammation of the gastric compartments, or esophageal and gastric ulcers. Studies also indicated that BUT was more cytotoxic to some cell lines in vitro. Although the exact mechanism of butenolide toxicity is not completely elucidated, studies indicated that butenolide caused lipid peroxidation reaction and accumulation of its metabolic products of the experimental animals.1.Toxicity of BUT to myocardium and primary culture myocytesThe cytotoxicity of BUT was examined using primary myocytes cultures from neonatal rat. Cell viability was determined by the methyllthiazolte- trazolium(MTT) dye assay. The results demonstrated myocytes were sensitive to the cytotoxic effects of BUT and the 12h LC50 values of BUT was 53μg/ml. On morphological examination, the butenolide-treated cells show significant changes, cells had cuboidal forms. 18 male Wistar rats were oral administrated with 0,10 or 20mg/kg /d BUT for two months respectively. After dosing, all animals were euthanized for histopathology examination. The histopathological characteristics of animal hearts shows coagulation necrosis and colliquative necrosissome in heart of 10 and 20mg/kg groups. We also observed the decreased activity of the Na~+K~+—ATPase and Ca~2+Mg~2+—ATPase of myocytes membrane.2.lipid peroxidation effectsof BUT in myocardium...