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

Autor:	Duicu OM; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania.; b Center for Translational Research and Systems Medicine, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, Timişoara, Romania., Privistirescu A; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania., Wolf A; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania., Petruş A; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania., Dănilă MD; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania.; b Center for Translational Research and Systems Medicine, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, Timişoara, Romania., Raţiu CD; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania., Muntean DM; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania.; b Center for Translational Research and Systems Medicine, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, Timişoara, Romania., Sturza A; a Department of Functional Sciences - Pathophysiology, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, 2, Eftimie Murgu Sq., Timişoara 300041, Romania.; b Center for Translational Research and Systems Medicine, 'Victor Babeş' University of Medicine and Pharmacy of Timişoara, Timişoara, Romania.
Jazyk:	angličtina
Zdroj:	Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2017 Nov; Vol. 95 (11), pp. 1376-1382. Date of Electronic Publication: 2017 Jul 24.
DOI:	10.1139/cjpp-2017-0074
Abstrakt:	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 2 O 2 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 2 O 2 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 H 2 O 2 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.
Databáze:	MEDLINE
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