Gender differences in oesophageal mucosal injury in a reflux oesophagitis model of rats

Masaka, Tomohiro; Iijima, Katsunori; Endo, Hiroyuki; Asanuma, Kiyotaka; Ara, Nobuyuki; Ishiyama, Fumitake; Asano, Naoki; Koike, Tomoyuki; Imatani, Akira; Shimosegawa, Tooru

doi:10.1136/gutjnl-2011-301389

Cited by 58 publications

(52 citation statements)

References 56 publications

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“…However, only mild tissue dam-age has been observed in female rats. 10 Furthermore, exogenous 17β-estradiol binding and signaling through E2 receptors attenuated esophageal tissue damage in males and ovariectomized rats through reducing mast cell-mediated cytotoxicity and the production of cytokines, specifically TNF-a that drives inflammation. 10 In contrast, treatment with 17a-estradiol that binds E2 receptors but does not induce downstream signaling has no effect on tissue damage.…”

Section: Immune Responsementioning

confidence: 99%

“…10 Furthermore, exogenous 17β-estradiol binding and signaling through E2 receptors attenuated esophageal tissue damage in males and ovariectomized rats through reducing mast cell-mediated cytotoxicity and the production of cytokines, specifically TNF-a that drives inflammation. 10 In contrast, treatment with 17a-estradiol that binds E2 receptors but does not induce downstream signaling has no effect on tissue damage. 10 While esophageal damage was more severe in ovariectomized rats compared to sham ovariectomized rats, the aggravated esophageal damage could be weakened by 17β-estradiol.…”

Section: Immune Responsementioning

confidence: 99%

“…In addition, a significant male-predominance in esophageal tissue damage by exogenous nitric oxide (NO) has been found. 10 In male rats, severe esophageal ulcers and inflammation with polymorphonuclear cell and lymphocyte infiltrates have been induced by exogenous NO. However, only mild tissue dam-age has been observed in female rats.…”

Section: Immune Responsementioning

confidence: 99%

“…61 Estrogen has been revealed to have anti-inflammatory activity which contributes to tissue resistance in females in animal models. 10,61 Recently, Masaka et al 10 explored the role of estrogen (E2) in protecting esophageal damage in a chronic rat reflux esophagitis model. In addition, a significant male-predominance in esophageal tissue damage by exogenous nitric oxide (NO) has been found.…”

Section: Immune Responsementioning

confidence: 99%

“…7 Meanwhile, reflux symptoms and NERD generally affect more women than men. 7,9 Epidemiological data have suggested that the esophageal mucosal epithelium is more fragile to refluxed gastroduodenal contents in men compared to that of women, 7,10 although women are more susceptible to GERD symptoms than men. Sex means a human's biological status based on their reproductive systems and functions assigned by chromosomal type.…”

Section: Introductionmentioning

confidence: 99%

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Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

128

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It is important to understand sex and gender-related differences in gastroesophageal reflux disease (GERD) because gender-related biologic factors might lead to better prevention and therapy. Non-erosive reflux disease (NERD) affects more women than men. GERD symptoms are more frequent in patients with NERD than in those with reflux esophagitis. However, men suffer pathologic diseases such as reflux esophagitis, Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) more frequently than women. The prevalence of reflux esophagitis is significantly increased with age in women, especially after their 50s. The mean age of EAC incidence in women is higher than in men, suggesting a role of estrogen in delaying the onset of BE and EAC. In a chronic rat reflux esophagitis model, nitric oxide was found to be an aggravating factor of esophageal injury in a male-predominant way. In addition, the expression of esophageal occludin, a tight junction protein that plays an important role in the esophageal defense mechanism, was up-regulated in women. This explains the male predominance of reflux esophagitis and delayed incidence of BE or EAC in women. Moreover, the symptoms such as heartburn, regurgitation, and extra-esophageal symptoms have been more frequently reported by women than by men, suggesting that sex and gender play a role in symptom perception. Differential sensitivity with augmented symptoms in women might have diagnostic and therapeutic influence. Furthermore, recent studies have suggested that hormone replacement therapy has a protective effect against esophageal cancer. However, an anti-inflammatory role of estrogen remains compelling, which means further study is necessary in this area.

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Section: Immune Responsementioning

confidence: 99%

Section: Immune Responsementioning

confidence: 99%

Section: Immune Responsementioning

confidence: 99%

Section: Immune Responsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex and Gender Differences in Gastroesophageal Reflux Disease

Kim

2016

J Neurogastroenterol Motil

128

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Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: An analysis of SEER‐Medicare data

Drahos

Ricker

Pfeiffer

et al. 2016

Cancer

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Background Metabolic syndrome (MetS) is associated with cancer risk and increases the risk of Barrett’s esophagus, the precursor lesion of esophageal adenocarcinoma (EA), primarily in the absence of gastroesophageal reflux disease (GERD). However, little is known about whether MetS is associated with risk of EA. Methods Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database we evaluated whether MetS was associated with EA. EA cases (n=3,167) were compared with individually matched population controls (5:1); a subset of EA cases (n=575) were able to be individually matched to Barrett’s esophagus controls (n=575). MetS was defined using ICD-9-CM codes in the period 1–3 years prior to EA diagnosis or control selection. Unconditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Potential effect-modification by GERD symptoms and sex was examined in stratified models. Results EA was significantly associated with MetS (OR: 1.16, 95%CI: 1.06, 1.26) compared with population controls. In males, the association was restricted to those without prior GERD, however in females MetS was associated with EA regardless of GERD status. Effect modification by sex was observed (p-interaction=0.01). MetS was not associated with EA risk when compared with Barrett’s esophagus controls. Conclusions In this older population, MetS was associated with an increased risk of EA in males without GERD and females regardless of GERD status. Given the lack of an association when compared with Barrett’s esophagus controls, MetS may impact EA risk by primarily increasing risk of the precursor lesion Barrett’s esophagus.

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Critical Evaluation of Animal Models of Gastrointestinal Disorders

Johnson

Meerveld

2017

Handbook of Experimental Pharmacology

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Preclinical research remains an important tool for discovery and validation of novel therapeutics for gastrointestinal disorders. While in vitro assays can be used to verify receptor-ligand interactions and test for structural activity of new compounds, only whole-animal studies can demonstrate drug efficacy within the gastrointestinal system. Most major gastrointestinal disorders have been modeled in animals; however the translational relevance of each model is not equal. The purpose of this chapter is to provide a critical evaluation of common animal models that are being used to develop pharmaceuticals for gastrointestinal disorders. For brevity, the models are presented for upper gastrointestinal disorders involving the esophagus, stomach, and small intestine and lower gastrointestinal disorders that focus on the colon. Particular emphasis is used to explain the face and construct validity of each model, and the limitations of each model, including data interpretation, are highlighted. This chapter does not evaluate models that rely on surgical or other non-pharmacological interventions for treatment.

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Gender differences in oesophageal mucosal injury in a reflux oesophagitis model of rats

Cited by 58 publications

References 56 publications

Sex and Gender Differences in Gastroesophageal Reflux Disease

Sex and Gender Differences in Gastroesophageal Reflux Disease

Metabolic syndrome and risk of esophageal adenocarcinoma in elderly patients in the United States: An analysis of SEER‐Medicare data

Critical Evaluation of Animal Models of Gastrointestinal Disorders

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