Estrogen-Dependent Nrf2 Expression Protects Against Reflux-Induced Esophagitis.

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.

AIMS:

This study aimed to clarify the role of Nrf2 in reflux-induced esophageal inflammation, focusing on the gender difference and nitric oxide.

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.

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.

CONCLUSIONS:

Estrogen-dependent Nrf2 expression might contribute to protection against the development of gastroesophageal reflux disease in females.

• Authors: Yudai Torihata, Kiyotaka Asanuma, Katsunori Iijima, Tetsuhiko Mikami, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 63 Issue 2 Pg. 345-355 (02 2018) ISSN: 1573-2568 [Electronic] United States
• PMID: 29282639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• NF-E2-Related Factor 2
• Estradiol

Topics

• Animals
• Antibodies
• Cell Line, Tumor
• Esophageal Neoplasms
• Esophagitis, Peptic (etiology, pathology)
• Esophagus (pathology)
• Estradiol (administration & dosage, pharmacology)
• Female
• Gastroesophageal Reflux (complications)
• Gene Expression Regulation (drug effects)
• Humans
• Male
• NF-E2-Related Factor 2 (genetics, metabolism)
• Rats
• Rats, Inbred F344
• Sex Factors