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      The Protective Effect of Teprenone on Aspirin-Related Gastric Mucosal Injuries

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          Abstract

          Objective

          Aspirin usage is associated with increased risk of gastrointestinal bleeding. The present study explored the potential of teprenone, an antiulcerative, in preventing aspirin-related gastric mucosal injuries.

          Methods

          280 patients with coronary diseases, naïve to aspirin medication, were admitted between 2011 and 2013 at the First Affiliated Hospital of Zhejiang Chinese Medical University and randomized into two groups ( n = 140). The aspirin group received aspirin enteric-coated tablets 100 mg/day, while the aspirin+teprenone group received teprenone 50 mg 3 times/day along with aspirin. The patients were recorded for gastrointestinal symptoms and gastric mucosal injuries during a follow-up period of 12 months with 3-month intervals.

          Results

          During the 3-month follow-up, no significant difference was observed in the incidence rate of gastrointestinal symptoms between the two groups ( P = 0.498). However, the incidence rate of gastrointestinal symptoms was significantly lower in the aspirin+teprenone group than in the aspirin group during the follow-ups at 6 months ( P = 0.036) and 12 months ( P = 0.036). The incidence rate of gastric mucosal injuries in the aspirin group was significantly increased at 12 months compared to that at 3 months ( P = 0.016). The incidence rates at 12 months and cumulative for the entire follow-up period in the aspirin+teprenone group were both significantly lower than those of the aspirin group ( P = 0.049 and P = 0.001, respectively).

          Conclusion

          Long-term use of low-dose aspirin causes varying degrees of gastric mucosal damages and gastrointestinal symptoms; the severity will increase within a certain range with the extension of medication duration. Teprenone mitigates the gastrointestinal symptoms caused by low-dose aspirin, lowering both the incidence and severity of gastric mucosal injuries and exerting a positive protective effect.

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          Most cited references36

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          Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.

          J R Vane (1971)
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            Final report on the aspirin component of the ongoing Physicians' Health Study. Steering Committee of the Physicians' Health Study Research Group.

            The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial designed to determine whether low-dose aspirin (325 mg every other day) decreases cardiovascular mortality and whether beta carotene reduces the incidence of cancer. The aspirin component was terminated earlier than scheduled, and the preliminary findings were published. We now present detailed analyses of the cardiovascular component for 22,071 participants, at an average follow-up time of 60.2 months. There was a 44 percent reduction in the risk of myocardial infarction (relative risk, 0.56; 95 percent confidence interval, 0.45 to 0.70; P less than 0.00001) in the aspirin group (254.8 per 100,000 per year as compared with 439.7 in the placebo group). A slightly increased risk of stroke among those taking aspirin was not statistically significant; this trend was observed primarily in the subgroup with hemorrhagic stroke (relative risk, 2.14; 95 percent confidence interval, 0.96 to 4.77; P = 0.06). No reduction in mortality from all cardiovascular causes was associated with aspirin (relative risk, 0.96; 95 percent confidence interval, 0.60 to 1.54). Further analyses showed that the reduction in the risk of myocardial infarction was apparent only among those who were 50 years of age and older. The benefit was present at all levels of cholesterol, but appeared greatest at low levels. The relative risk of ulcer in the aspirin group was 1.22 (169 in the aspirin group as compared with 138 in the placebo group; 95 percent confidence interval, 0.98 to 1.53; P = 0.08), and the relative risk of requiring a blood transfusion was 1.71. This trial of aspirin for the primary prevention of cardiovascular disease demonstrates a conclusive reduction in the risk of myocardial infarction, but the evidence concerning stroke and total cardiovascular deaths remains inconclusive because of the inadequate numbers of physicians with these end points.
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              Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself?

              Except in rare cases, the stomach can withstand exposure to highly concentrated hydrochloric acid, refluxed bile salts, alcohol, and foodstuffs with a wide range of temperatures and osmolarity. This is attributed to a number of physiological responses by the mucosal lining to potentially harmful luminal agents, and to an ability to rapidly repair damage when it does occur. Since the discovery in 1971 that prostaglandin synthesis could be blocked by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), there has been great interest in the contribution of prostaglandins to gastric mucosal defense. Prostaglandins modulate virtually every aspect of mucosal defense, and the importance of this contribution is evident by the increased susceptibility of the stomach to injury following ingestion of an NSAID. With chronic ingestion of these drugs, the development of ulcers in the stomach is a significant clinical concern. Research over the past two decades has helped to identify some of the key events triggered by NSAIDs that contribute to ulcer formation and/or impair ulcer healing. Recent research has also highlighted the fact that the protective functions of prostaglandins in the stomach can be carried out by other mediators, in particular the gaseous mediators nitric oxide and hydrogen sulfide. Better understanding of the mechanisms through which the stomach is able to resist injury in the presence of luminal irritants is helping to drive the development of safer anti-inflammatory drugs, and therapies to accelerate and improve the quality of ulcer healing.
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                Author and article information

                Contributors
                Journal
                Gastroenterol Res Pract
                Gastroenterol Res Pract
                GRP
                Gastroenterology Research and Practice
                Hindawi
                1687-6121
                1687-630X
                2019
                18 June 2019
                : 2019
                : 6532876
                Affiliations
                1Department of Gastroenterology, First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Road, Hangzhou 310006, China
                2Key Laboratory of Digestive Pathophysiology of Zhejiang Province, First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China
                Author notes

                Academic Editor: Haruhiko Sugimura

                Author information
                https://orcid.org/0000-0002-4481-9080
                https://orcid.org/0000-0001-9554-0541
                https://orcid.org/0000-0002-1429-157X
                https://orcid.org/0000-0003-2160-9176
                https://orcid.org/0000-0001-5346-0164
                https://orcid.org/0000-0001-8117-3007
                https://orcid.org/0000-0002-6247-571X
                Article
                10.1155/2019/6532876
                6604287
                11a09ea6-ab35-4609-8e63-0c7e38588ca0
                Copyright © 2019 Jing Zhao et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 July 2018
                : 28 November 2018
                Categories
                Research Article

                Gastroenterology & Hepatology
                Gastroenterology & Hepatology

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