title: Toxic effects of T-2 toxin and deoxynivalenol on the mitochondrial electron transport system of cardiomyocytes in rats.
abstract: 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.
authors.affiliation: Department of Comparative Pathophysiology, Division of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
authors.forename: Suchitra
authors.initials: S
authors.lastname: Ngampongsa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hanafusa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ando
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tsuru
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsubone
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000648:ultrastructure*; D010101:Oxygen Consumption / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013605:T-2 Toxin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014255:Trichothecenes / Q000037:antagonists & inhibitors / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D014255:Trichothecenes; D000255:Adenosine Triphosphate; D002374:Catalase; D013605:T-2 Toxin; C007262:deoxynivalenol; D001205:Ascorbic Acid