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Exploring the Gastroprotective, Ulcer Healing and Chemopreventive Properties of Nitric Oxide-Releasing Nonsteroidal Anti-inflammatory Drugs

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Nitric Oxide: From Research to Therapeutics

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 22))

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Abstract

Nitric oxide (NO) is a pleiotropic endogenous mediator in the gastrointestinal (GI) tract that is produced by the three NO-synthase (NOS) enzymes; neuronal (nNOS, NOS1), inducible (iNOS, NOS2), mainly involved in the inflammation response and endothelial (eNOS, NOS3), which regulates blood flow and mucosal defense against damage. NO contributes to the maintenance of mucosal integrity, gastrointestinal protection and ulcer healing, and therefore, the NO-based therapies have recently been proposed. The non-steroidal anti-inflammatory drugs (NSAIDs) exert anti-inflammatory, analgesic, anti-pyrogenic and chemopreventive properties, but their use is limited due to serious side effects such as GI-bleedings, mucosal erosions, and even gastric and duodenal ulceration. Thus, the strategy of incorporating a NO-releasing molecule into an NSAID has been shown to abolish the gastric side effects of native NSAIDs, presenting with lower gastric toxicity despite inhibiting both, prostaglandin cyclooxygenase (COX)-1 and COX-2 activity in the stomach. For example, new adducts of NO donor drugs that inhibit COX (CINODS, such as NO-aspirin, NO-ibuprofen and NO-sulindac) have shown better tolerability, less gastrointestinal damage and reduced hepatic toxicity of the parent drugs, also providing better cardiovascular safety compared to selective COX-2 inhibitors (coxibs). Moreover, such adducts prompted research into the anti-carcinogenic potential of NO-NSAID, as these novels NO-NSAID adducts can inhibit cell proliferation either directly or through their effect on COX isoenzymes. Here we review some of the most promising recent advances in NO-NSAID physiology and pharmacology, focusing on the protective and chemopreventive mechanism of these novel NO-NSAID prodrugs. Hopefully, this new class of NO-releasing anti-inflammatory agents could offer a new therapeutic and chemopreventive approach to counteracting the gastrointestinal adverse effects associated with NSAIDs.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Jagiellonian University Medical College, 16 Grzegorzecka Str., 31-531, Cracow, Poland

    Jolanta Majka & Tomasz Brzozowski

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  1. Jolanta Majka
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  2. Tomasz Brzozowski
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Correspondence to Tomasz Brzozowski .

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Editors and Affiliations

  1. Department of Pharmacology, Hamdard Institute of Medical Sciences and Research, Hamdard University, New Delhi, India

    Arunabha Ray

  2. Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, India

    Kavita Gulati

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Majka, J., Brzozowski, T. (2023). Exploring the Gastroprotective, Ulcer Healing and Chemopreventive Properties of Nitric Oxide-Releasing Nonsteroidal Anti-inflammatory Drugs. In: Ray, A., Gulati, K. (eds) Nitric Oxide: From Research to Therapeutics. Advances in Biochemistry in Health and Disease, vol 22. Springer, Cham. https://doi.org/10.1007/978-3-031-24778-1_18

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