Toxic effects of T-2 toxin and deoxynivalenol on the mitochondrial electron transport system of cardiomyocytes in rats.

The in vitro effects of 2 representative mycotoxins, T-2 toxin and deoxynivalenol (DON), of trichothecene group on the electron transport system (ETS) of mitochondria in rat cardiomyocytes were investigated by measuring oxygen consumption rates (OCR). The ATP-linked OCR and the reserve capacity (RC) of the mitochondria ETS were quantified by a "mitochondria stress test" which was estimated by the OCR responses to oligomycin and carbonyl cyanide-p-trifluoromethoxyphenylhydrazone, with an extracellular flux analyzer. The basal OCR was significantly inhibited by the application of T-2 toxin at concentrations of 6 × 10⁻¹ to 6 × 10⁻5 µM and DON at concentrations of 0.78 to 100 µM for 24 hr. The threshold of cardiomyocyte toxicity was estimated to be between 6.0 × 10⁻6 and 6.0 × 10⁻5 µM for T-2 toxicity on both ATP-linked OCR and RC and between 0.39 and 0.78 µM on ATP-linked OCR or between 1.56 and 3.13 µM on RC for DON. The decrease in OCR of cardiomyocytes exposed to T-2 toxin with a concentration of 6.0 × 10⁻³ and 6.0 × 10⁻4 µM was significantly inhibited by antioxidants, catalase and vitamin C. In conclusion, the present study demonstrated, through the direct and real-time measurement of respiratory function in mitochondria, that a marked inhibition of mitochondrial ETS function in cardiomyocytes was induced by T-2 toxin and DON and that the mitochondrial dysfunction by T-2 toxin was largely associated with oxidative stress.

Reevaluation of arrhythmias and alterations of the autonomic nervous activity induced by T-2 toxin through telemetric measurements in unrestrained rats.

This study was conducted to clarify and reevaluate the cardiac and autonomic nervous effects of T-2 toxin, which had been previously examined by several acute experiments, in unrestrained and conscious rats implanted with telemetric transmitters. Two groups of rats were given two subcutaneous injections of 0.1 and 0.5 mg/kg of T-2 toxin with an interval of 3 days. Two other groups of rat were pre-implanted with osmotic minipumps by which atropine (20 mg/kg/day) or propranolol (100 mg/kg/day) was continuously administered preceding subcutaneous injection of T-2 toxin (0.5 mg/kg). The present study demonstrated that T-2 toxin caused marked arrhythmias, such as second-degree atrioventricular (AV) block, sinus bradycardia, supraventricular extrasystole, and ventricular extrasystole, which were accompanied by a significant increase in heart rate and a significant decrease in total power and low- and high-frequency power of heart rate variability, during 3 days of observation after the toxin administration. However, the occurrence of arrhythmia with conduction disturbance such as second-degree atrioventricular blocks was markedly diminished by pretreatment with atropine, while the occurrence of ventricular extrasystole was augmented by atropine. The present study with the telemetric measurement elucidated and confirmed that T-2 toxin produced significant cardiac dysfunctions involving disturbance of the conduction pathway influenced by the autonomic nervous activity and also possible direct effects on cardiac myocytes.

Arrhythmias and alterations in autonomic nervous function induced by deoxynivalenol (DON) in unrestrained rats.

This study aimed to determine the cardiac and autonomic nervous effects of deoxynivalenol (DON), a representative mycotoxin which frequently contaminates cereal grains, in conscious rats that had been implanted with telemetric transmitters. Four groups of rats given subcutaneous injections of 0.5, 1.0, or 2.0 mg/kg of DON or propylene glycol (vehicle solution) were used in the experiments. Telemetric electrocardiogram (ECG) recordings were performed for 2 weeks or longer during the pre- and post-DON injection period. The present study demonstrated that DON caused marked arrhythmias, such as second-degree atrioventricular block, atrial bradycardia, supraventricular extrasystole, and ventricular extrasystole, at 3 hr or later (mostly at 10-20 hr) after the DON-injection, which were accompanied by a significant increase in heart rate (HR) and a significant decrease in total power and low- and high-frequency power during the period from 90 to 180 min after the injection. In conclusion, it was elucidated that DON produces significant cardiac dysfunction and transient inhibition of the autonomic nervous function in conscious rats at a dose of 0.5 mg/kg s.c. or more.