T1142 Aggravation by Selective Serotonin Re-Uptake Inhibitor of Antral Ulcers Induced by Indomethacin in Rats: Pathogenic Importance of Impaired Anti-Oxidative System

Kojo, Azusa; Nukui, Kazuo; Tanaka, Akiko; Amagase, Kikuko; Takeuchi, Koji

doi:10.1016/s0016-5085(10)62297-4

Cited by 2 publications

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“…Studies have suggested a risk of adverse gastric reactions to SSRIs, showing frequent gastrointestinal bleeding in patients taking SSRIs and a markedly increased risk of bleeding with the coadministration of NSAIDs (Dalton et al, 2003;De Jong et al, 2003;Mort et al, 2006;Lewis et al, 2008;Ahsberg et al, 2010;Dall et al, 2010), although there is controversy about the association (Tata et al, 2005;Itatsu et al, 2011). Consistent with the clinical findings, we found that SSRIs, given as a single injection, markedly aggravated the development of antral lesions in response to indomethacin in refed rats (Kojo et al, 2010). Several models of antral lesions have been established with various agents, including NSAIDs, and the pathogenesis of these models is reportedly associated with the impairment of the mucosal antioxidative system, such as a decrease in superoxide dismutase (SOD) activity or an increase in oxyradical production (Oka et al, 1991;Chen et al, 1993;Ohashi et al, 2009).…”

Section: Introductionsupporting

confidence: 87%

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Takeuchi

Tanaka²,

Nukui³

et al. 2011

J Pharmacol Exp Ther

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Recent clinical studies have suggested a risk of adverse gastric reactions from the concomitant use of selective serotonin (5-HT) reuptake inhibitors (SSRIs) with nonsteroidal anti-inflammatory drugs (NSAIDs). We examined the adverse effects of SSRIs on antral lesions produced by indomethacin in rats. Rats fasted for 24 h were refed for 1 h, then administered indomethacin (30 mg/kg s.c.) 1 h after the refeeding and killed 6 h later. Paroxetine (1-10 mg/kg) was given orally 30 min before indomethacin. Indomethacin caused antral lesions in refed rats. Paroxetine dose-dependently aggravated these lesions, despite provoking no damage by itself. Similar results were obtained when other NSAIDs such as diclofenac, flurbiprofen, and loxoprofen were coadministered with paroxetine or when indomethacin was coadministered with other antidepressants such as fluvoxamine and milnacipran, but not imipramine or maprotiline. Exogenous 5-HT also worsened the indomethacin-induced antral damage, whereas the aggravating effect of paroxetine was attenuated by ondansetron, a selective 5-HT 3 antagonist, but not antagonists for other 5-HT receptor subtypes. Indomethacin plus paroxetine had no effect on gastric secretion but significantly decreased mucosal superoxide dismutase (SOD) activity as well as GSH content. The antral damage induced by indomethacin plus paroxetine was significantly prevented by antisecretory (acid or pepsin) agents and mucosal protective agents as well as SOD and allopurinol. These results suggest that SSRIs aggravate NSAID-induced antral lesions, probably via the activation of 5HT 3 receptors, and the mechanism of aggravation may involve the corrosive action of acid/ pepsin as well as an impaired antioxidative system.

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Section: Introductionsupporting

confidence: 87%

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Takeuchi

Tanaka²,

Nukui³

et al. 2011

J Pharmacol Exp Ther

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“…The mechanisms by which SSRI aggravate NSAID-induced gastroduodenal injury have been poorly investigated. In an animal model the SSRI Paroxetine™ increased the severity of indomethacin-induced antral ulcers by impairing anti-oxidative systems (decrease in gastric mucosal superoxide dismutase and glutathione content) [ 22 ].…”

Section: Risk Factors For Nsaid-induced Gastroduodenal Bleedingmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Bleeding: Risk Factors and Prevention Strategies

2010

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed medications in the World. A frequent complication of NSAID use is gastroduodenal bleeding. Risk factors for gastroduodenal bleeding while on NSAID therapy are age, prior peptic ulcer and co-medication with anti-platelet agents, anticoagulants, glucocorticosteroids and selective serotonin-reuptake inhibitors (SSRI). Prevention strategies for at-risk patients include the use of the lowest effective dose of NSAIDs, co-therapy with proton-pump inhibitors and/or the use of a COX-2 selective agent. Treatment of Helicobacter pylori infection is beneficial for primary prophylaxis of NSAID-induced gastroduodenal bleeding in NSAID-naive patients. For patients with cardiovascular risk factors requiring NSAIDs, naproxen should be selected. In very high risk patients for both gastrointestinal and cardiovascular complications NSAID therapy should be avoided altogether.

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T1142 Aggravation by Selective Serotonin Re-Uptake Inhibitor of Antral Ulcers Induced by Indomethacin in Rats: Pathogenic Importance of Impaired Anti-Oxidative System

Cited by 2 publications

References 0 publications

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Aggravation by Paroxetine, a Selective Serotonin Reuptake Inhibitor, of Antral Lesions Generated by Nonsteroidal Anti-Inflammatory Drugs in Rats

Nonsteroidal Anti-Inflammatory Drug-Induced Gastroduodenal Bleeding: Risk Factors and Prevention Strategies

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