Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts

• Published in: Canadian journal of physiology and pharmacology Vol. 95; no. 11; pp. 1376 - 1382
• Main Authors: Duicu, Oana M, Privistirescu, Andreea, Wolf, Adrian, Petruş, Alexandra, Dănilă, Maria D, Raţiu, Corina D, Muntean, Danina M, Sturza, Adrian
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.11.2017; Canadian Science Publishing NRC Research Press
• Subjects: Animals; Care and treatment; Cell Respiration - drug effects; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Dosage and administration; Electron transport; Heart; Hydrogen Peroxide - metabolism; Male; Methylene blue; Methylene Blue - pharmacology; Mitochondria; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Oxidative stress; Oxidative Stress - drug effects; Patient outcomes; Pharmacology; Physiological aspects; Physiology; Rats; Rats, Sprague-Dawley; Rodents; methylene blue; diabète sucré; dérivés réactifs de l’oxygène; mitochondrie de cœur de rat; reactive oxygen species; rat heart mitochondria; bleu de méthylène; diabetes mellitus; respiration mitochondriale; mitochondrial respiration
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2017-0074

Diabetic cardiomyopathy has been systematically associated with compromised mitochondrial energetics and increased generation of reactive oxygen species (ROS) that underlie its progression to heart failure. Methylene blue is a redox drug with reported protective effects mainly on brain mitochondria. The purpose of the present study was to characterize the effects of acute administration of methylene blue on mitochondrial respiration, H O production, and calcium sensitivity in rat heart mitochondria isolated from healthy and 2 months (streptozotocin-induced) diabetic rats. Mitochondrial respiratory function was assessed by high-resolution respirometry. H O production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L ) elicited an increase in oxygen consumption of mitochondria energized with complex I and II substrates in both normal and diseased mitochondria. Interestingly, methylene blue elicited a significant increase in H O release in the presence of complex I substrates (glutamate and malate), but had an opposite effect in mitochondria energized with complex II substrate (succinate). No changes in the calcium retention capacity of healthy or diabetic mitochondria were found in the presence of methylene blue. In conclusion, in cardiac mitochondria isolated from diabetic and nondiabetic rat hearts, methylene blue improved respiratory function and elicited a dichotomic, substrate-dependent effect on ROS production.