What is Gastroesophageal Reflux Disease (GERD)?

Gastroesophageal reflux disease (GERD), commonly referred to as heartburn, is a chronic digestive disorder characterized by the reflux of stomach acid and other gastric contents into the esophagus, leading to symptoms such as heartburn, regurgitation, and chest discomfort. GERD occurs when the lower esophageal sphincter (LES), a ring of muscle at the junction between the esophagus and the stomach, fails to close properly or relaxes abnormally, allowing stomach contents to flow back up into the esophagus.


What is the relationship between GERD and oxidative stress?

The relationship between gastroesophageal reflux disease (GERD) and oxidative stress involves complex interactions between various factors that contribute to tissue damage, inflammation, and the progression of esophageal complications associated with GERD. Here’s how oxidative stress may be related to GERD:


  • Reactive Oxygen Species (ROS) Production: Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms in the esophageal mucosa. ROS, such as superoxide radicals, hydrogen peroxide, and hydroxyl radicals, can be generated during normal cellular metabolism or in response to external factors such as inflammation, acid exposure, or tissue injury. Excessive production of ROS in the esophageal epithelial cells can lead to oxidative damage to lipids, proteins, and DNA, contributing to tissue inflammation and injury in GERD.


  • Esophageal Inflammation: GERD is characterized by chronic exposure of the esophageal mucosa to stomach acid and other gastric contents, leading to inflammation and tissue damage. Oxidative stress can activate inflammatory pathways and stimulate the release of pro-inflammatory cytokines, chemokines, and inflammatory mediators in the esophageal mucosa. Chronic inflammation in the esophagus is a hallmark of GERD and can exacerbate oxidative stress, disrupt mucosal integrity, and impair tissue repair mechanisms, leading to complications such as esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma.


  • Mucosal Defense Mechanisms: The esophageal mucosa possesses natural antioxidant defense mechanisms to neutralize ROS and maintain redox homeostasis. However, during GERD, the balance between ROS production and antioxidant defenses may be disrupted, leading to oxidative stress and tissue damage. Inadequate intake of dietary antioxidants or depletion of antioxidant reserves due to chronic inflammation or acid exposure may further exacerbate oxidative stress in individuals with GERD.


  • DNA Damage and Mutagenesis: Oxidative stress can cause DNA damage and mutations in esophageal epithelial cells, increasing the risk of genetic alterations and malignant transformation. Chronic exposure to acid and bile reflux in GERD can lead to the accumulation of DNA damage and genetic instability, contributing to the progression of Barrett’s esophagus and the development of esophageal adenocarcinoma, a complication associated with long-standing GERD.


Overall, oxidative stress plays a critical role in the pathogenesis of GERD by promoting inflammation, disrupting mucosal integrity, impairing tissue repair mechanisms, and contributing to the progression of esophageal complications such as Barrett’s esophagus and esophageal adenocarcinoma.