S1627 Induction of Antral Ulcers By Alendronate, a Nitrogen-Containing Bisphosponate, in Rat Stomachs

Ohashi, Yumi; Aihara, Eitaro; Amagase, Kikuko; Takeuchi, Koji

doi:10.1016/s0016-5085(08)61098-7

Cited by 14 publications

(45 citation statements)

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“…The correlation between GI AE with increased pH and inflammation has been confirmed in these models using gastro protective and anti-inflammatory agents, showing a decrease in the occurrence and magnitude of these AE [43][44][45][46][47][48]. Thus, in the last years, different oral formulations than tablets have been tested and proposed for osteoporosis treatment [49].…”

Section: New Alendronate Formulationmentioning

confidence: 81%

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

2014

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Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

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Section: New Alendronate Formulationmentioning

confidence: 81%

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

2014

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“…ALD also increases the TNF-a level that causes neutrophil infiltration and activation to generate ROS [42]. Other authors verified that severity of gastric lesions induced by ALD was reduced by treatment with allopurinol, suggesting the involvement of oxyradical production in this pathogenesis [43]. Thus, it seems that the ulcerogenic response in the antrum is related to the dysfunction of the anti-oxidative mechanism.…”

Section: Discussionmentioning

confidence: 96%

“…In fact, the white cap that covers the damaged mucosa is composed mainly of inflammatory cells and fibrin-like substances [28]. Other studies have reported that toxic effects of ALD in the stomach have been linked to a direct effect of this agent on the mucosal surface [28,29]. Additionally, when ALD is applied to the gastric mucosa, it decreases transmucosal potential difference of the stomach, which is suggestive of a direct disruption of surface epithelial cells [30].…”

Section: Discussionmentioning

confidence: 99%

“…However, ALD-induced neutrophil accumulation and subepithelial edema in the gastric mucosa have been shown to play major roles in the development of ulcers [27]. In fact, the white cap that covers the damaged mucosa is composed mainly of inflammatory cells and fibrin-like substances [28]. Other studies have reported that toxic effects of ALD in the stomach have been linked to a direct effect of this agent on the mucosal surface [28,29].…”

Section: Discussionmentioning

confidence: 99%

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Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats

Carvalho

Silva

et al. 2015

Dig Dis Sci

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“…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). However, the mechanism underlying the aggravation by SSRIs of NSAID-induced antral damage remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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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S1627 Induction of Antral Ulcers By Alendronate, a Nitrogen-Containing Bisphosponate, in Rat Stomachs

Cited by 14 publications

References 0 publications

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

Protective Effects of Simvastatin Against Alendronate-Induced Gastric Mucosal Injury in Rats

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

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