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

Duicu, Oana; Privistirescu, Andreea; Wolf, Adrian; Mioc, Alexandra; Dănilă, Mirela; Ratiu, Corina; Muntean, Daniela-Lucia; Sturza, Adrian

doi:10.1139/cjpp-2017-0074

Cited by 24 publications

(22 citation statements)

References 33 publications

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“…Drugs that alter the mitochondrial activity usually lead to loss of parasite ATP production and induction of apoptosis [42]. For example, MB improves mitochondrial respiration in cells [35, 43], decreasing ROS in cardiac tissue from diabetic rats [44].…”

Section: Resultsmentioning

confidence: 99%

Phenothiazinium Dyes Are Active againstTrypanosoma cruziIn Vitro

Portapilla

Pereira

Costa

et al. 2019

BioMed Research International

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Chagas disease is a tropical illness caused by the protozoan Trypanosoma cruzi. The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti-T. cruzi effects of phenothiazinium dyes in amastigote and trypomastigote forms of the parasite. Methylene Blue, New Methylene Blue, Toluidine Blue O, and 1,9-Dimethyl Methylene Blue inhibited the parasite proliferation at nanomolar concentrations and also demonstrated low toxicity in host cells. Moreover, combinations of phenothiazinium dyes indicated a synergic pattern against amastigotes compared to the Benznidazole counterparts. Phenothiazinium dyes levels of reactive oxygen species (ROS) and decreased the mitochondrial potential in trypomastigotes, indicating the mechanism of action of the dyes in T. cruzi. Our article offers a basis for future strategies for the control of Chagas disease using low-cost formulations, an important point for endemic underdeveloped regions.

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Section: Resultsmentioning

confidence: 99%

Phenothiazinium Dyes Are Active againstTrypanosoma cruziIn Vitro

Portapilla

Pereira

Costa

et al. 2019

BioMed Research International

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“…As reported, both MB and PBM are known to enhance energy production and decrease oxidative stress [294][295][296]. However, the underlying mechanism for these effects differs between the two treatments.…”

Section: Primary Mechanisms Underlying Mitochondrial Protection Through Mb and Pbmmentioning

confidence: 88%

Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation

Yang

Youngblood

et al. 2020

Transl Neurodegener

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Mitochondrial dysfunction plays a central role in the formation of neuroinflammation and oxidative stress, which are important factors contributing to the development of brain disease. Ample evidence suggests mitochondria are a promising target for neuroprotection. Recently, methods targeting mitochondria have been considered as potential approaches for treatment of brain disease through the inhibition of inflammation and oxidative injury. This review will discuss two widely studied approaches for the improvement of brain mitochondrial respiration, methylene blue (MB) and photobiomodulation (PBM). MB is a widely studied drug with potential beneficial effects in animal models of brain disease, as well as limited human studies. Similarly, PBM is a non-invasive treatment that promotes energy production and reduces both oxidative stress and inflammation, and has garnered increasing attention in recent years. MB and PBM have similar beneficial effects on mitochondrial function, oxidative damage, inflammation, and subsequent behavioral symptoms. However, the mechanisms underlying the energy enhancing, antioxidant, and anti-inflammatory effects of MB and PBM differ. This review will focus on mitochondrial dysfunction in several different brain diseases and the pathological improvements following MB and PBM treatment.

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“…Likewise, the revelation of a novel helpful procedure for the advancement and upkeep of a mitochondrial work is of extraordinary logical significance in the treatment of DCM [8]. High generation of reactive oxygen species (ROS) is the main cause of progression to cardiac brokenness when mitochondrial vitality is impaired [9]. Recently, oxidative stress has been recognized as a risk factor in the progressing of diabetic cardiovascular complications [10].…”

Section: Introductionmentioning

confidence: 99%

Phosphocreatine Improves Cardiac Dysfunction by Normalizing Mitochondrial Respiratory Function through JAK2/STAT3 Signaling Pathway In Vivo and In Vitro

Qaed

Wang

Almoiliqy

et al. 2019

Oxidative Medicine and Cellular Longevity

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Diabetic cardiomyopathy (DCM) is one of the common cardiovascular complications in patients with diabetes. Accumulating evidence has demonstrated that DCM is thoroughly related to mitochondrial energy impairment and increases the generation of reactive oxygen species (ROS). Therefore, an ongoing study is developing strategies to protect cardiac mitochondria from diabetic complications, especially from hyperglycemia. Phosphocreatine (PCr) plays a major metabolic role in cardiac muscular cells including intracellular concentration of ATP which affects the activity of the myocardium. We hypothesized that PCr might improve oxidative phosphorylation and electron transport capacity in mitochondria impaired by hyperglycemia in vivo and in vitro. Also, we aimed to evaluate the protective effect of PCr against DCM through the JAK2/STAT3 signaling pathway. The mitochondrial respiratory capacity from rats and H9C2 cells was measured by high-resolution respirometry (HRR). Expressions of proteins Bax, Bcl-2, caspase 3, caspase 9, cleaved caspase 3, and cleaved caspase 9, as well as JAK2/STAT3 signaling pathways, were determined by western blotting. ROS generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Type 1 diabetes mellitus was induced in Wistar male rats by a single intraperitoneal injection of streptozotocin (STZ) (80 mg/kg body weight). Our results revealed that PCr possessed protective effects against DCM injury by improving the mitochondrial bioenergetics and by positively exerting protective effects against DCM in vivo and in vitro, not only improving diabetes symptom, resulting in changes of cardiac tissue using hematoxylin and eosin (H&E) stain, but also ameliorating biochemical changes. Moreover, PCr increased Bcl-2, caspase 3, and caspase 9 protein expressions and decreased Bax, cleaved caspase 3, and cleaved caspase 9 expressions as well as the JAK2/STAT3 signaling pathway. In conclusion, PCr improves mitochondrial functions and exerts an antiapoptotic effect in vivo and in vitro exposed to oxidative stress by hyperglycemia through the JAK2/STAT3 signaling pathway. Our findings suggest that PCr medication is a possible therapeutic strategy for cardioprotection.

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

Cited by 24 publications

References 33 publications

Phenothiazinium Dyes Are Active againstTrypanosoma cruziIn Vitro

Phenothiazinium Dyes Are Active againstTrypanosoma cruziIn Vitro

Mitochondria as a target for neuroprotection: role of methylene blue and photobiomodulation

Phosphocreatine Improves Cardiac Dysfunction by Normalizing Mitochondrial Respiratory Function through JAK2/STAT3 Signaling Pathway In Vivo and In Vitro

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