Effects of veratrine on skeletal muscle mitochondria: ultrastructural, cytochemical, and morphometrical studies.
The alkaloid veratrine is a lipid-soluble neurotoxin, which target voltage-gated Na+ channels for their primary action. Recently, we showed that this alkaloid may cause myonecrosis and evidences suggest mitochondria as one of its cell targets. Herein, we investigate the effects caused by variable concentration of veratrine (250 and 550 microg/mL) on mitochondrial oxygen consumption, respiratory chain enzymes activities, and ultrastructure, combining electron microscopy with cytochemical and biochemical approaches. The results showed different sort of ultrastructural changes, both in isolated and intramuscular mitochondria. Veratrine decreased mitochondrial nicotinamide adenine dinucleotide dehydrogenase (NADH-d), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) activities, significantly and dose-dependently inhibited the state 3 respiration rate, respiratory control ratio (RCR), and ADP/O on isolated rat skeletal muscle mitochondria, whereas state 4 was unaffected. A tendency of increase in mitochondria diameter was seen with 250 microg/mL veratrine. We conclude that the alkaloid would probably act on mitochondrial membrane phospholipid configuration, which would explain the changes observed.
Freitas
Erika Maria Silva
EM
Departamento de Histologia e Embriologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-970, Brazil.
Fagian
Márcia M
MM
da Cruz-Höfling
Maria Alice
MA
D000818:Animals; D004579:Electron Transport / Q000502:physiology; D003576:Electron Transport Complex IV / Q000032:analysis; D006651:Histocytochemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000187:drug effects; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D009245:NADH Dehydrogenase / Q000032:analysis; D010101:Oxygen Consumption; D051381:Rats; D013385:Succinate Dehydrogenase / Q000032:analysis; D014702:Veratrine / Q000633:toxicity*
D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D014702:Veratrine