Stimulation of respiration by methylene blue in rat liver mitochondria.
The effect of methylene blue on isolated rat liver mitochondria in the presence and absence of chloroacetaldehyde was investigated. Fatty acid oxidation was inhibited by chloroacetaldehyde and subsequently stimulated by methylene blue. Assessment of tightly coupled mitochondria revealed decreasing respiratory control ratios induced by increasing concentrations of methylene blue and methylene blue provoked mitochondrial swelling. In uncoupled mitochondria, methylene blue promoted a concentration-dependent stimulation of respiration. These findings provide evidence that methylene blue, the redox dye currently used as an antidote for encephalopathy associated with alkylating chemotherapy, uncouples oxidative phosphorylation and acts as an electron transfer mediator to stimulate mitochondrial respiration.
Visarius
T M
TM
Department of Clinical Pharmacology, University of Berne, Switzerland. theresa@mem.unibe.ch
Stucki
J W
JW
Lauterburg
B H
BH
D000079:Acetaldehyde / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000931:Antidotes; D004396:Coloring Agents; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000494:pharmacology
D000931:Antidotes; D004396:Coloring Agents; D014475:Uncoupling Agents; C004656:chloroacetaldehyde; D000079:Acetaldehyde; D008751:Methylene Blue