Animal models of rheumatoid arthritis (RA) are widely used for testing potential new therapies for RA. The most commonly used models of human RA are adjuvant-induced arthritis (AIA) and collagen-induced arthritis in rats and mice. In this chapter, we will focus on inflammatory and oxidative stress (OS) processes during the development of AIA. OS is a result of increased production of reactive oxygen species (ROS) or a reduction in the body’s endogenous antioxidant defense system. ROS and reactive nitrogen species (RNS) can contribute to the pathogenesis of RA by the induction of membrane oxidation, irreversible damage to proteins and DNA, cartilage damage, and induction of bone resorption. ROS/RNS can also modulate a variety of signaling events that control gene expression and affect cellular processes that participate in chronic inflammation. Our research team has been studying the course of OS during the development of rat AIA for more than a decade. We have analyzed the course of OS using markers of lipid peroxidation (malondialdehyde, 4-hydroxy-2-nonenal, and F-2 isoprostanes), protein carbonyls, antioxidant enzymes (heme oxygenase and gamma-glutamyl transferase), and levels of endogenous antioxidants (coenzyme Q10 and Q9, gamma-tocopherol) in plasma and different tissues (joint, liver, lung, skeletal muscle, and spleen).
Part of the book: Animal Models in Medicine and Biology
The host immune response generates the pro-inflammatory immune response as a protective measure against invading pathogens, allergens, and/or trauma. However, dysregulated and chronic inflammation may result in secondary damage to tissues and immune pathology to the host. Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease which primarily involves synovial inflammation, joint pain, immobility, and stiffness. Increased infiltration of inflammatory immune cells and fibroblast-like synoviocytes into joints, form pannus and small blood vessels that lead to synovium and cartilage destruction. In this chapter we will focus on the role of inflammatory cytokines (IL-1β, IL-6 and IL-17), chemokine monocyte chemotactic protein-1 and matrix metalloproteinase-9 in the pathogenesis of experimental arthritis in animals and in human RA. Further, we will be discussing about methotrexate’s (cornerstone of anti-rheumatic therapy) immune suppressing activity, anti-inflammatory properties of carnosic acid and extract of Rhodiola rosea L., and their innovative combination treatments with methotrexate in rat adjuvant arthritis.
Part of the book: Inflammation in the 21st Century