Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase activity? A contribution to the ongoing discussion

Bilska‐Wilkosz, Anna; Kotańska, Magdalena; Górny, Magdalena; Filipek, Barbara; Iciek, Małgorzata

doi:10.18388/abp.2019_2908

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…The available literature data indicate that during the reaction of hydrolysis GTN to 1,2-glyceryl dinitrate and nitrite (NO 2 − ), ALDH2 undergoes oxidative inhibition, causing down-regulation of this enzyme which is associated with GTN tolerance [ 16 ]. Thus, in the opinion of many authors, ALDH2 activity is a useful marker of cardiovascular oxidative stress, but the concept is still under discussion [ 17 ].…”

Section: Commentarymentioning

confidence: 99%

A commentary on the paper: ‘Evaluation of spice and herb as phytoderived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method’

Bilska‐Wilkosz

2022

Bioscience Reports

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It is commonly known that aldehyde dehydrogenases (ALDHs) are a promising therapeutic target in many diseases. Bui et al. - the authors of the paper I am discussing here (Biosci Rep (2021) 41(5): BSR20210491; DOI: https://doi.org/10.1042/BSR20210491) - point that there is a lack of research on the use of spices and herbs as the sources of naturally occurring modulators of ALDH activity. In order to carry out this type of research, the authors prepared ethanolic extracts of 22 spices and herbs. The main objective of the study was to investigate retinaldehyde dehydrogenases (RALDHs), of which retinal is the main substrate and ALDH2, the mitochondrial isoform, having acetaldehyde as the main substrate. The obtained results indicated that the tested extracts exhibited differential regulatory effects on RALDHs/ALDH2 and some of them showed a potential selective inhibition of the activity of RALDHs.

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Section: Commentarymentioning

confidence: 99%

A commentary on the paper: ‘Evaluation of spice and herb as phytoderived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method’

Bilska‐Wilkosz

2022

Bioscience Reports

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“…Suitable reductants include dithiothreitol (DTT) [72,73], mercaptoethanol [22], cysteine, and N-acetylcysteine [12,31], but not glutathione [66,74]. In addition, ALDH2 can be partially restored by dihydrolipoic acid, which is a metabolic reductant present in mitochondria [13,74,75].…”

Section: The Active Site Of Mitochondrial Aldehyde Dehydrogenasementioning

confidence: 99%

Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance

Pearson

Butler

2021

Molecules

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Glyceryl trinitrate (GTN) is one of the earliest known treatments for angina with a fascinating history that bridges three centuries. However, despite its central role in the nitric oxide (NO) story as a NO-donating compound, establishing the precise mechanism of how GTN exerts its medicinal benefit has proven to be far more difficult. This review brings together the explosive and vasodilatory nature of this three-carbon molecule while providing an update on the likely in vivo pathways through which GTN, and the rest of the organic nitrate family, release NO, nitrite, or a combination of both, while also trying to explain nitrate tolerance. Over the last 20 years the alcohol detoxification enzyme, aldehyde dehydrogenase (ALDH), has undoubtedly emerged as the front runner to explaining GTN’s bioactivation. This is best illustrated by reduced GTN efficacy in subjects carrying the single point mutation (Glu504Lys) in ALDH, which is also responsible for alcohol intolerance, as characterized by flushing. While these findings are significant for anyone following the GTN story, they appear particularly relevant for healthcare professionals, and especially so, if administering GTN to patients as an emergency treatment. In short, although the GTN puzzle has not been fully solved, clinical study data continue to cement the importance of ALDH, as uncovered in 2002, as a key GTN activator.

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“…Based on the previous findings, the objective of this research was to study the potential effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester ( l -NAME), a nitric oxide inhibitor on acute liver damage and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [ 3 H]-thymidine incorporation in rats induced by a single necrogenic dose of TAA. GTN is a strong vasorelaxant and NO donor and is degraded to mono-and di-nitrate isomers [ 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

Is Glyceryl Trinitrate, a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?

Ahmed

Ahmed²,

Vun-Sang

et al. 2022

Molecules

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Oxidative stress induced by well-known toxins including ferric nitrilotriacetate (Fe-NTA), carbon tetrachloride (CCl4) and thioacetamide (TAA) has been attributed to causing tissue injury in the liver and kidney. In this study, the effect of glyceryl trinitrate (GTN), a donor of nitric oxide and NG-nitroarginine methyl ester (l-NAME), a nitric oxide inhibitor on TAA-induced hepatic oxidative stress, GSH and GSH-dependent enzymes, serum transaminases and tumor promotion markers such as ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats were examined. The animals were divided into seven groups consisting of six healthy rats per group. The six rats were injected intraperitoneally with TAA to evaluate its toxic effect, improvement in its toxic effect if any, or worsening in its toxic effect if any, when given in combination with GTN or l-NAME. The single necrogenic dose of TAA administration caused a significant change in the levels of both hepatic and serum enzymes such as glutathione S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), γ-glutamyl transpeptidase (GGT), glucose 6-phosphate dehydrogenase (G6PD), alanine aminotransferase (AST) and aspartate aminotransferase (ALT). In addition, treatment with TAA also augmented malondialdehyde (MDA), ornithine decarboxylase (ODC) activity and [3H]-thymidine incorporation in rats liver. Concomitantly, TAA treatment depleted the levels of GSH. However, most of these changes were alleviated by the treatment of animals with GTN dose-dependently. The protective effect of GTN against TAA was also confirmed histopathologically. The present data confirmed our earlier findings with other oxidants including Fe-NTA and CCl4. The GTN showed no change whatsoever when administered alone, however when it was given along with TAA then it showed protection thereby contributing towards defending the role against oxidants-induced organ toxicity. Overall, GTN may contribute to protection against TAA-induced oxidative stress, toxicity, and proliferative response in the liver, according to our findings.

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Is the mechanism of nitroglycerin tolerance associated with aldehyde dehydrogenase activity? A contribution to the ongoing discussion

Cited by 3 publications

References 26 publications

A commentary on the paper: ‘Evaluation of spice and herb as phytoderived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method’

A commentary on the paper: ‘Evaluation of spice and herb as phytoderived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method’

Glyceryl Trinitrate: History, Mystery, and Alcohol Intolerance

Is Glyceryl Trinitrate, a Nitric Oxide Donor Responsible for Ameliorating the Chemical-Induced Tissue Injury In Vivo?

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