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

Can J Physiol Pharmacol. 2017 Nov;95(11):1376-1382. doi: 10.1139/cjpp-2017-0074. Epub 2017 Jul 24.


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, H2O2 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. H2O2 production and calcium retention capacity were measured spectrofluorimetrically. The addition of methylene blue (0.1 μmol·L-1) 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 H2O2 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.

Keywords: bleu de méthylène; diabetes mellitus; diabète sucré; dérivés réactifs de l’oxygène; methylene blue; mitochondrial respiration; mitochondrie de cœur de rat; rat heart mitochondria; reactive oxygen species; respiration mitochondriale.

MeSH terms

  • Animals
  • Cell Respiration / drug effects*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Hydrogen Peroxide / metabolism
  • Male
  • Methylene Blue / pharmacology*
  • Mitochondria, Heart / drug effects*
  • Mitochondria, Heart / metabolism*
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Hydrogen Peroxide
  • Methylene Blue