Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to anti-hypertrophic effects

Lucas, Aline Maria Brito; Caldas, Francisco Rodrigo de Lemos; Silva, Amanda P. da; Ventura, Maximiano M.; Leite, Iago Mateus Rocha; Filgueiras, Ana B.; Silva, Claúdio G.L.; Kowaltowski, Alicia J.; Facundo, Heberty T.

doi:10.1016/j.cbi.2016.11.012

Cited by 25 publications

(21 citation statements)

References 36 publications

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“…In addition to cytoprotective effects well documented in the literature, DZ was shown to represent a promising pharmacological intervention against cytotoxicity of the drugs known to cause severe impairment of mitochondria, such as isoproterenol and doxorubicin [8,66]. Moderation of ROS production ensuing from DZ administration [8,64,66] was shown to be a part of cytoprotective action.…”

Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 89%

“…So, suppression of ATP hydrolysis due to the down modulation of F 0 F 1 ATP synthase [19] and the inhibition of cellular ATPases seem to be helpful in preventing cellular ATP depletion under ischemia [15,18], while the suppression of ATP synthesis likely could help to keep K ATP channels in highly active state in order to afford cytoprotection via mild uncoupling, SDH inhibition, suppression of ROS overproduction [8,17,20,64] and the inhibition of permeability transition pore activity [8,63]. At last, PKC activation was shown to exert several cytoprotective actions via cell-signaling pathways [63,65].…”

Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 99%

“…Moderation of ROS production ensuing from DZ administration [8,64,66] was shown to be a part of cytoprotective action. However, no direct evidence for the involvement of mK ATP channel in cytoprotection was yet obtained in living organism.…”

Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 99%

“…This implies that DZ administration should result in the modulation of mitochondrial functions, ensuing from mK ATP channel opening and affect mitochondrial bioenergetics as it was shown in the heart, brain, liver, and pancreatic beta-cells [8][9][10]. But while the opening of mK ATP channel is generally thought to be cytoprotective, appraisal of bioenergetic and functional effects of mK ATP channel opening in mitochondria using DZ as pharmacological tool, is complicated by several side effects of this drug [2,11].…”

Section: Introductionmentioning

confidence: 99%

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Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Акопова¹

2017

J Drug Metab Toxicol

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Diazoxide (DZ) is a well-known cardioprotective drug capable of mimicking ischemic preconditioning. Being primarily a pharmacological opener of mitochondrial ATP-sensitive potassium channels (mK ATP channels), DZ is known to produce multiple side effects because of its interactions with different cellular targets (such as plasma membrane K ATP channels, F 0 F 1 ATP synthase, succinate dehydrogenase and others), capable of confounding an understanding of direct bioenergetic effects of mK ATP channels opening in mitochondria. In this review direct and offtarget effects of DZ were discussed. The emphasis was made on molecular basis of DZ interaction with K ATP channels and different K ATP channels isoforms sensitivity to this drug. The present knowledge on DZ interaction with mK ATP channels is outlined as well as DZ interactions with other molecular targets affecting mitochondrial functions and bioenergetics. Conclusion was reached that high sensitivity of mK ATP channel to DZ allows for avoiding offtarget effects of this drug in studies on isolated mitochondria, which makes it a useful tool in an appraisal of diverse functional effects of mK ATP channel opening.

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Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 89%

Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 99%

Section: Nonspecific Cellular Targets Of Diazoxidementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Акопова¹

2017

J Drug Metab Toxicol

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“…The maintenance of cell redox state is important to cell viability [43]. The increased level of reactive species can lead to oxidative damage to a vast number of biological molecules, as DNA [44][45][46], proteins [47], lipids [48], including membranes [3] leading to a range of pathologies, as cancer [36], neurological disease [49], cardiac disease [50,51], inflammation process [52] and aging.…”

Section: Cellular Respiration and Generation Of Reactive Species In Tmentioning

confidence: 99%

Oxidative Stress: Noxious but Also Vital

Bagatini¹,

Jaques²,

Oliveira³

et al. 2018

Novel Prospects in Oxidative and Nitrosative Stress

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The imbalance between reactive oxygen species (ROS) production and antioxidant defenses determines the condition called oxidative stress. When there is an increase in ROS production or a decrease in the antioxidant defenses, this systemic antioxidant/pro-oxidant imbalance may lead to the accumulation of oxidative damage, which, in turn, may lead to a modification of biomolecules. These consist of reactions resulting in protein adducts, DNA oxidation, and formation of lipid peroxides, which, in turn, reduce the cellular functional capacity and increase the risk of disease development. The body has natural scavenging systems against free radicals and other reactive species. However, sometimes the endogenous antioxidant capacity is exceeded by the production of ROS. When this occurs, exogenous antioxidants exert important function for the human health. These bioactive compounds act preventing and neutralizing the formation of new reactive species and free radical s .I ns o m ec a s e s ,a n increase of ROS can help the host to resolve an infection or even to control the tumor growth. Finally, the levels of ROS can be perceived by signal transduction pathways involving known targets(i.e.,p53,Ras,andNF-κB) and regulate physiopathological events such as the cellular cycle, apoptosis, and inflammation.Keywords: reactive species, cellular oxidation, antioxidant system, health, disease © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cellular respiration and generation of reactive species in the mitochondria: implications in cell viability and agingOxidative phosphorylation is the center of energy metabolism in plants, animals and several microbial life forms [1]. In eukaryotes, this process occurs in mitochondria. The mitochondria is a cytoplasmic organelle surrounded by two membranes, outer and inner membrane, which main function is the production of most of the phosphate compounds necessary for the energetic balance of the cell. In addition, other functions such as the regulation of the body'sheatgeneration [2][3][4] programmed cell death [5][6][7], reactive oxygen species (ROS) generation and cell signaling [8] is also associated with mitochondria. Cellular vitality is directly related to mitochondria, and mitochondrial dysfunctions are frequent causes of accidental cell death [5,[9][10][11], cancer [12, 13], diabetes [14][15][16] and neurodegenerative diseases [17][18][19], among others.The characterization of the respiratory electron chain could be performed in studies using the fractionation of its components by certain detergents that at low concentrations break the interactions between proteins and lipids in the membranes, leaving associations between proteins intact [20]. In electron transport chain, through this process, four protein complexes were found....

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Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy

Alexandre

Viana

David

et al. 2020

Naunyn-Schmiedeberg's Arch Pharmacol

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Diazoxide prevents reactive oxygen species and mitochondrial damage, leading to anti-hypertrophic effects

Cited by 25 publications

References 36 publications

Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Direct and Off-Target Effects of ATP-Sensitive Potassium Channels Opener Diazoxide

Oxidative Stress: Noxious but Also Vital

Quercetin treatment increases H2O2 removal by restoration of endogenous antioxidant activity and blocks isoproterenol-induced cardiac hypertrophy

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