Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.
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PMID:Esophagitis in Sprague-Dawley rats is mediated by free radicals. 879 7

Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to malignant degeneration is clinically important. Glutathione s-transferase (GST)-pi belongs to a class of protective enzymes whose activity has been shown to be much lower in Barrett's metaplasia than in the normal esophagus, where this form of GST is predominant. In the studies described here, using immunocytochemical analysis, we observed higher levels of cytoplasmic GST-pi protein in normal esophageal mucosa than in Barrett's metaplasia. Using northern blot analysis, we also observed lower GST-pi mRNA levels in Barrett's metaplasia than in normal esophagus or adenocarcinomas from the same patients. Using as model systems three Barrett's adenocarcinoma cell lines and short-term organ culture of freshly resected normal esophagus and Barrett's metaplasia, dose-dependent induction of GST-pi mRNA was observed by using butylated hydroxyanisole and dexamethasone. GST-pi mRNA in Barrett's metaplasia was induced up to 2.5-fold with 60 microM butylated hydroxyanisole and nearly fivefold with 320 nM dexamethasone after 24 h. These studies demonstrate the ability to induce protective GST-pi in Barrett's metaplasia and may suggest a mechanism for future chemoprevention studies in patients with this type of epithelium, which is at high risk for malignant degeneration.
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PMID:Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines. 1007 40

This study is the first to examine site-specific changes in mucosal antioxidants and expression and localization of heat shock proteins (HSPs) following the induction of subacute esophagitis and after recovery using an established animal model. Distal, middle, and proximal samples were excised from anesthetized opossums 24 hr after three consecutive days of 45-min perfusion with saline or 100 mmol/liter HCI, or seven days after acid in recovery animals. Compared to controls, acid-induced erosive esophagitis significantly increased glutathione peroxidase and HSP90 at all sites and HSP60 proximally. Reduced glutathione was significantly decreased distally, as was HSP72 at distal and middle sites. No changes in superoxide dismutase or catalase occurred. After recovery, superoxide dismutase, catalase, and HSP expression were not different from controls. Glutathione peroxidase and glutathione were significantly decreased distally. Similar differential stress responses may occur in patients with chronic gastroesophageal reflux and could be important in the pathogenesis of reflux esophagitis.
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PMID:Analysis of mucosal stress response in acid-induced esophagitis in opossum. 1218 45

Reflux esophagitis is a common complication of the gastroesophageal reflux disease. Glutathione s-transferases (GSTs) have important role in the protection of cells from the products of oxidative stress. GSTP1*B allele has a correlation with susceptibility to several diseases. In this case-control study, the role and frequency of GSTP1 polymorphism was evaluated in Iranian patients with erosive reflux esophagitis. Seventy patients with erosive reflux esophagitis and 75 normal individuals were enrolled in this study. The grade of esophagitis was determined via endoscopy. DNA was extracted from venous blood of each subject using the salting out method. GSTP1 genetic polymorphisms were detected using the polymerase chain reaction restriction fragment length polymorphism method. There was a significant difference in GSTP1 genotype frequency between patients and normal groups (P= 0.006). Also, in the patient group, the grade B of esophagitis was significantly associated with variant GSTP1 genotype (P= 0.028). The rate of throat pain symptom was higher in the no-variant group (P < 0.036). The GSTP1*B allele frequency in Iranian normal groups is similar to Orientals. Reflux esophagitis are more commonly found in variant (*B/*B and *A/*B) GSTP1 genotypes. In addition, GSTP1 polymorphism is correlated with a higher grade of esophagitis.
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PMID:The role and frequency of glutathione s-transferase P1 polymorphism in Iranian patients affected with reflux esophagitis. 2045 48