What is ulcerative colitis?

Ulcerative colitis is a chronic inflammatory bowel disease (IBD) characterized by inflammation and ulceration of the inner lining of the colon and rectum. It is one of the two main types of IBD, the other being Crohn’s disease. Ulcerative colitis primarily affects the colon (large intestine) and the rectum, leading to symptoms such as abdominal pain, diarrhea, rectal bleeding, and urgency to have a bowel movement.


The exact cause of ulcerative colitis is unknown, but it is believed to involve a combination of genetic, environmental, and immune factors. The condition is thought to result from an abnormal immune response in which the body’s immune system mistakenly attacks the lining of the colon and rectum, leading to inflammation and tissue damage.


What is the relationship between ulcerative colitis and oxidative stress?

The relationship between ulcerative colitis (UC) and oxidative stress is complex and multifaceted. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses, leading to cellular damage. In UC, oxidative stress plays a significant role in the pathogenesis and progression of the disease by contributing to inflammation, tissue damage, and dysfunction of the colon. Here’s how oxidative stress may be involved in UC:


  • Immune Activation and Inflammation: In UC, the immune system becomes dysregulated, leading to chronic inflammation in the colon. Activated immune cells, such as neutrophils, macrophages, and T cells, produce ROS as part of the inflammatory response. ROS can amplify inflammation by activating inflammatory signaling pathways, promoting cytokine production, and recruiting additional immune cells to the inflamed tissue. Chronic inflammation and oxidative stress contribute to tissue damage, ulceration, and loss of barrier function in the colon.


  • Epithelial Damage and Barrier Dysfunction: The epithelial lining of the colon serves as a barrier that protects the underlying tissue from luminal contents, including bacteria and toxins. Oxidative stress can impair the integrity of the epithelial barrier by damaging tight junction proteins, disrupting cell-cell adhesion, and compromising barrier function. Increased permeability of the intestinal epithelium allows bacterial antigens and inflammatory mediators to penetrate the mucosal barrier, triggering immune responses and perpetuating inflammation in UC.


  • Leukocyte Activation and ROS Production: In UC, leukocytes, particularly neutrophils and macrophages, are recruited to the inflamed colonic mucosa and contribute to tissue damage through the production of ROS and other reactive species. Activated neutrophils release ROS as part of the respiratory burst, which is essential for microbial killing but can also damage surrounding tissues and exacerbate inflammation. Macrophages activated in the inflamed mucosa produce ROS and pro-inflammatory cytokines, perpetuating the inflammatory cascade in UC.


  • Mitochondrial Dysfunction: Oxidative stress can lead to mitochondrial dysfunction in colonic epithelial cells and immune cells, impairing energy production, redox signaling, and cellular homeostasis. Mitochondrial dysfunction exacerbates oxidative stress, promotes inflammation, and contributes to tissue injury and dysfunction in UC.


  • Antioxidant Defenses: Imbalance between ROS production and antioxidant defenses in UC contributes to oxidative stress and tissue damage. Reduced levels of antioxidants, such as superoxide dismutase, catalase, and glutathione, compromise the ability of the colon to neutralize ROS and protect against oxidative damage. Decreased antioxidant capacity in UC may result from genetic factors, dietary deficiencies, or impaired antioxidant enzyme activity.


Overall, oxidative stress is a central mechanism underlying the pathogenesis of ulcerative colitis, contributing to inflammation, tissue damage, and barrier dysfunction in the colon.