What is Rheumatoid Arthritis (RA)?

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that primarily affects the joints. In RA, the body’s immune system mistakenly attacks the synovium, the lining of the membranes that surround the joints, causing inflammation and thickening of the synovium. This chronic inflammation leads to joint damage, pain, stiffness, swelling, and loss of function over time.


RA can affect multiple joints throughout the body, but it most commonly affects the small joints of the hands, wrists, and feet. However, larger joints such as the knees, shoulders, and hips can also be affected. In addition to joint symptoms, RA can also cause systemic manifestations, including fatigue, fever, weight loss, and overall malaise.


The exact cause of rheumatoid arthritis is not fully understood, but it is believed to involve a combination of genetic, environmental, and hormonal factors. Certain genetic factors may predispose individuals to developing RA, while environmental triggers such as infections, smoking, and exposure to certain pollutants may also play a role in triggering the immune response that leads to inflammation in the joints.


What is the relationship between RA and oxidative stress?

The relationship between rheumatoid arthritis (RA) and oxidative stress is complex and multifaceted. Oxidative stress, which refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to detoxify or neutralize them, is known to play a significant role in the pathogenesis and progression of RA. Several factors contribute to oxidative stress in RA:


  • Inflammation: Chronic inflammation is a hallmark feature of RA and is associated with increased production of ROS by activated immune cells, such as macrophages and neutrophils, within the inflamed synovial tissue. These ROS can cause damage to joint tissues, including cartilage, bone, and synovium, contributing to the progression of joint damage and deformity in RA.


  • Mitochondrial Dysfunction: Mitochondria, the energy-producing organelles within cells, are major sources of ROS. In RA, mitochondrial dysfunction may occur in various cell types, including immune cells and synovial fibroblasts, leading to increased ROS production and oxidative stress. Mitochondrial dysfunction can further exacerbate inflammation and tissue damage in RA.


  • Dysregulated Antioxidant Defenses: Antioxidant enzymes and molecules, such as superoxide dismutase, catalase, glutathione peroxidase, and vitamins C and E, play a crucial role in neutralizing ROS and protecting cells from oxidative damage. However, in RA, antioxidant defenses may become overwhelmed or dysregulated, leading to increased oxidative stress and cellular damage.


  • Protein and Lipid Oxidation: Oxidative stress in RA can result in the oxidation of proteins and lipids within joint tissues, leading to structural and functional changes that contribute to joint damage and inflammation. Protein oxidation can alter the function of enzymes and signaling molecules involved in inflammatory pathways, while lipid oxidation can disrupt cell membranes and promote the release of pro-inflammatory mediators.


  • DNA Damage: ROS can also cause damage to DNA within joint cells, leading to genetic mutations and dysregulation of gene expression. DNA damage and oxidative stress-induced epigenetic changes may contribute to the perpetuation of inflammation and tissue damage in RA.


Overall, oxidative stress is intimately linked to the pathogenesis and progression of RA, contributing to inflammation, tissue damage, and joint destruction in the disease.