Multitarget Antioxidant NO-Donor Organic Nitrates: A Novel Approach to Overcome Nitrates Tolerance, an Ex Vivo Study

Elisabetta Marini; Marta Giorgis; Marta Leporati; Barbara Rolando; Konstantin Chegaev; Loretta Lazzarato; Massimo Bertinaria; Marco Vincenti; Antonella Di Stilo

doi:10.3390/antiox11010166

Antioxidants (Jan 2022)

Multitarget Antioxidant NO-Donor Organic Nitrates: A Novel Approach to Overcome Nitrates Tolerance, an Ex Vivo Study

Elisabetta Marini,
Marta Giorgis,
Marta Leporati,
Barbara Rolando,
Konstantin Chegaev,
Loretta Lazzarato,
Massimo Bertinaria,
Marco Vincenti,
Antonella Di Stilo

Affiliations

Elisabetta Marini: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Marta Giorgis: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Marta Leporati: Regional Antidoping & Toxicology Center “Alessandro Bertinaria”, Regione Gonzole 10/1, I-10043 Orbassano, Italy
Barbara Rolando: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Konstantin Chegaev: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Loretta Lazzarato: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Massimo Bertinaria: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy
Marco Vincenti: Department of Chemistry, University of Turin, via Pietro Giuria 5, I-10125 Torino, Italy
Antonella Di Stilo: Department of Drug Science and Technology, University of Turin, via Pietro Giuria 9, I-10125 Torino, Italy

DOI: https://doi.org/10.3390/antiox11010166
Journal volume & issue: Vol. 11, no. 1
p. 166

Abstract

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Chronic use of glyceryl trinitrate (GTN) is limited by serious side effects, such as tolerance and endothelial dysfunction of coronary and resistance arteries. Although GTN is used as a drug since more than 130 years, the mechanisms of the vasodilatory effects and of tolerance development to organic nitrates are still incompletely elucidated. New synthesized organic nitrates with and without antioxidant properties were characterized for their ex vivo tolerance profile, in order to investigate the oxidative stress hypothesis of nitrate tolerance. The organic nitrates studied showed different vasodilation and tolerance profiles, probably due to the ability or inability of the compounds to interact with the aldehyde dehydrogenase-2 enzyme (ALDH-2) involved in bioactivation. Furthermore, nitrooxy derivatives endowed with antioxidant properties did not determine the onset of tolerance, even if bioactivated by ALDH-2. The results of this study could be further evidence of the involvement of ALDH-2 in the development of nitrate tolerance. Moreover, the behavior of organic nitrates with antioxidant properties supports the hypothesis of the involvement of ROS in inactivating ALDH-2.

Published in Antioxidants

ISSN: 2076-3921 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antioxidants

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Abstract

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