**4.2 Oxidative stress in adjuvant arthritis**

In the development of AIA, not only immunological and inflammatory pathological changes are involved, but also the redox homeostasis is shifted toward increased production of ROS and RNS. Overproduction of ROS and RNS damages lipids, proteins, and DNA (also exhausts the natural enzymatic and nonenzymatic antioxidant defense), which is possible to detect with different markers of oxidation in biological structures. In human RA OS-mediated damage to lipids, proteins, and DNA and changes in enzymatic and nonenzymatic antioxidant defense are extensively studied. AIA in animals resembles the OS caused damage in human rheumatic diseases; therefore, it is a very useful tool to study process of OS during autoimmune diseases. Since there has been no standard therapy to reduce OS damage in diseases established yet, AIA could be a promising candidate for developing this type of therapy.

elevated levels of F2-isoprostanes observed in such diseases. Quantification of F2 isoprostanes as pathophysiological markers is suitable for the investigation of lipid peroxidation in human diseases and provides an interesting biomarker of antioxidant efficacy in diseases where OS might be involved [59]. There are only few evidences about F2-isoprostanes in animal models of RA. In one of our previous experiments, we have measured an elevated level of F2-isoprostanes in plasma of AIA rats, which were significantly increased compared to control healthy animals [60]. In a CIA model, authors investigated the ability of grape seed proanthocyanidin extract (GSPE) to reduce the development of mice arthritis. They have found that CIA significantly increased the level of 8-isoprostane in plasma. Plasma levels of 8-isoprostane and serum level of collagen type II-specific IgG2a in GSPEtreated mice were significantly decreased than those in the control mice [61]. Authors demonstrated that F2-isoprostanes are increased also in the urine of CIA mice [62]. F2-isoprostanes as an important marker of lipid peroxidation should be more extensively studied in AIA animal models, to obtain a better picture about the

*Markers of oxidative stress (malondialdehyde (MDA) and 4-hydroxynonenal (HNE) in the brain of arthritic*

**Oxidative stress in brain MDA (μg/g tissue) HNE (ng/g tissue)** CO 5.38 0.73 3.26 0.17 AIA 10.12 1.01\*\*\* 4.78 0.5\*\* *Values are expressed as average standard error of mean, statistical significance (ANOVA-Tukey-Kramer post*

*Impact of Oxidative Stress on Inflammation in Rheumatoid and Adjuvant Arthritis: Damage…*

Protein carbonyls (aldehydes and ketones) are produced directly by oxidation or via reactions with other molecules generated by the oxidation process. Autoimmune attack, resulting from abrogation of self-tolerance, is involved in many human diseases. Autoimmune disease may be either organ specific (type 1 diabetes, thyroiditis, myasthenia gravis, and primary biliary cirrhosis) or systemic (RA, progressive systemic sclerosis, and systemic lupus erythematosus). Nearly all these diseases have autoantibodies. Autoantibodies are typically present several years prior to diagnosis of SLE and serve as markers for future disease. Inflammation, infection, drugs, ROS, and environmental factors induce formation of neo-antigens [63]. The protein thiol groups were 59% diminished by AIA. The protein carbonyls content, an indicative of protein damage, was increased by arthritis (41%). Protein damage in both liver and brain was estimated as the tissue content of protein carbonyl groups. Corroborating previous results, arthritis increased protein damage in both tissues, 55% in the liver and 51% in the brain [64]. Authors Hemshekhar et al. [65] also showed a significant decrease in total protein thiol content with reference to saline-fed rats up to 51 and 36.05%, respectively, in liver and spleen homogenates of arthritic rats [65]. In a study about protective effects of green tea extract in AIA rats, authors detected a significant OS-caused damage to proteins and lipids in the liver, brain, and plasma [66]. The antioxidant defense, reduced in arthritis, is improved by the green tea treatment, as shown in the restoration of the GSH and protein thiol levels and by the tendency for normalizing the activities of the antioxidant enzymes. In arthritis rats, we found a significant increase of protein carbonyls in plasma [66–69] (**Table 1**). This finding emphasizes the role of OS in

similarity with human RA.

*hoc test): \*\*p < 0.01, \*\*\*p < 0.01 vs. CO.*

*DOI: http://dx.doi.org/10.5772/intechopen.89480*

*animals measured on day 28).*

**Table 2.**

*4.2.2 Oxidation of proteins*

**203**
