8 research outputs found
Impact of Oxidative Stress on Inflammation in Rheumatoid and Adjuvant Arthritis: Damage to Lipids, Proteins, and Enzymatic Antioxidant Defense in Plasma and Different Tissues
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)
Inflammation in the Pathogenesis of Rheumatoid Arthritis and in Experimental Arthritis: Evaluation of Combinations of Carnosic Acid and Extract of <em>Rhodiola rosea</em> L. with Methotrexate
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
Pharmacological influence on processes of adjuvant arthritis: effect of the combination of an antioxidant active substance with methotrexate
Reduction of oxidative stress in adjuvant arthritis. Comparison of efficacy of two pyridoindoles: stobadine dipalmitate and SMe1.2HCl
The aim of this study was to evaluate the therapeutic potential of oxidative stress (OS) reduction by using pyridoindole (PI) antioxidants in adjuvant arthritis (AA). The substances tested were stobadine dipalmitate (STB) and SMe1. AA was used as animal model. The experiments included healthy animals, control arthritic animals and arthritic animals with administration of PI in the oral daily dose of 15 mg/kg b.m during 28 experimental days. The rats were sacrificed on day 28. Clinical and biochemical parameters were determined. The effect of PI administration was evaluated on the basis of the following parameters: (a) arthritis (volume of hind paws - HPW, change of animal body mass - CBM), (b) OS (chemiluminescence of whole blood - CWB, levels of thiobarbituric acid reacting substance - TBARS and of HNE- and MDA-protein adducts in plasma and activity of γ-glutamyltransferase (GGT) in hind paw joint homogenates). The PI studied significantly increased the CBM of animals and corrected the HPW. STB also significantly decreased the activity of GGT in joint homogenates. SMe1 was more effective in decreasing plasmatic TBARS levels, but STB was more effective in reducing plasmatic HNE- and MDA-protein adducts. The assay for HNE- and MDA-adducts in plasma as a function of time was applied for the first time in AA. STB markedly decreased spontaneous and PMA-stimulated CWB and reduced neutrophil count. In summary, STB was more effective than SMe1 in reducing OS in AA. Our results showed that the reduction of OS in arthritis also corrected the clinical manifestations of the disease
Combined methotrexate and coenzyme Q10 therapy in adjuvant-induced arthritis evaluated using parameters of inflammation and oxidative stress
Rheumatoid arthritis is a common severe joint disease that affects all age groups, it is thus of great importance to develop new strategies for its treatment. The aim of the present study was to examine the combined effect of coenzyme Q10 (CoQ10) and methotrexate (MTX) on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritis (AA) was induced by a single intradermal injection of heat-inactivated Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included healthy animals, arthritic animals not treated, arthritic animals treated with CoQ10, with methotrexate, and with a combination of CoQ10 and methotrexate. The two latter groups received a daily oral dose of 20 mg/kg b.w. of CoQ10, either alone or with methotrexate in an oral dose of 0.3 mg/kg b.w. twice a week. We found that CoQ10 potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect of methotrexate on the level of oxidation of proteins (suppression of protein carbonyl level in plasma) as well as lipoperoxidation (suppression of levels of HNE-adducts and MDA-adducts to plasma proteins). The same effect was observed for plasmatic levels of CoQ9 and IL-1α, and partially also for γ-glutamyltransferase activity assessed in joints and spleen. Moreover, the combination therapy improved the functionality of peripheral blood neutrophils in AA, with a balancing effect on the immunosuppression caused by MTX monotherapy. In summary, combined administration of CoQ10 and methotrexate suppressed arthritic progression in rats more effectively than did MTX alone. This finding may help improve treatment of rheumatoid arthritis
Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance
Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress. Unexpectedly, it was found that sarcoplasmic reticulum Ca2 +-ATPase (SERCA) activity was elevated in muscles of rats with AA compared to controls, suggesting possible conformational changes in the enzyme. There was no alteration in the nucleotide binding site but rather in the transmembrane domain according to the tryptophan polar/non-polar fluorescence ratio. Higher relative expression of SERCA, higher content of nitrotyrosine but no increase in phospholipid oxidation in AA SR was found. In vitro treatments of SR with HOCl showed that in AA animals SERCA activity was more susceptible to oxidative stress, but SR phospholipids were more resistant and SERCA could also be activated by phosphatidic acid. It was concluded that increased SERCA activity in AA was due to increased levels of SERCA protein and structural changes to the protein, probably induced by direct and specific oxidation involving reactive nitrogen species