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Estrogen-Dependent Nrf2 Expression Protects Against Reflux-Induced Esophagitis.
- Source :
-
Digestive diseases and sciences [Dig Dis Sci] 2018 Feb; Vol. 63 (2), pp. 345-355. Date of Electronic Publication: 2017 Dec 27. - Publication Year :
- 2018
-
Abstract
- Background: Gastroesophageal reflux disease is more common in males than in females. The enhanced antioxidative capacity of estrogen in females might account for the gender difference. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in the host defense mechanism against oxidative stress.<br />Aims: This study aimed to clarify the role of Nrf2 in reflux-induced esophageal inflammation, focusing on the gender difference and nitric oxide.<br />Methods: Gastroesophageal reflux was surgically induced in male and female rats. Nitrite and ascorbic acid were administered for 1 week to provoke nitric oxide in the esophageal lumen. Male rats with gastroesophageal reflux were supplemented with 17β-estradiol or tert-butylhydroquinone, an Nrf2-inducing reagent. Esophageal squamous cell carcinoma KYSE30 cells were treated with 17β-estradiol. Nrf2 expression was examined by Western blotting and quantitative real-time PCR. Antioxidant gene expression profiles were examined by a PCR array.<br />Results: In the presence of nitric oxide, reflux-induced esophageal damage was less evident, whereas esophageal expression of Nrf2 and its target genes such as Nqo1 was more evident in female or male rats supplemented with 17β-estradiol than in male rats. 17β-Estradiol increased nuclear Nrf2 expression in KYSE30 cells. tert-Butylhydroquinone increased tissue Nqo1 mRNA expression, leading to a reduction in reflux-induced esophageal damage.<br />Conclusions: Estrogen-dependent Nrf2 expression might contribute to protection against the development of gastroesophageal reflux disease in females.
- Subjects :
- Animals
Antibodies
Cell Line, Tumor
Esophageal Neoplasms
Esophagitis, Peptic pathology
Esophagus pathology
Estradiol administration & dosage
Female
Humans
Male
NF-E2-Related Factor 2 genetics
Rats
Rats, Inbred F344
Sex Factors
Esophagitis, Peptic etiology
Estradiol pharmacology
Gastroesophageal Reflux complications
Gene Expression Regulation drug effects
NF-E2-Related Factor 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2568
- Volume :
- 63
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Digestive diseases and sciences
- Publication Type :
- Academic Journal
- Accession number :
- 29282639
- Full Text :
- https://doi.org/10.1007/s10620-017-4885-3