*4.2.2 Oxidation of proteins*

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

inflammatory diseases such as AIA, not only in tissues directly affected by the disease (cartilage, bone, and skeletal muscle) (**Table 2**).

CoQ10 plays a central role in the electron transport chain and as a radicalscavenging antioxidant; therefore we studied its level in plasma during AA. In our experiments the arthritis process increased significantly the level of CoQ10 in comparison with healthy control rats. The arthritic processes also stimulated the synthesis of CoQ9 (dominant form of CoQ in rats) and its transport to plasma [79] (**Table 4**). In the skeletal muscle mitochondria, we have measured significant

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

Similarly in AIA, also in patients with RA, a depletion of endogenous antioxidants was measured. The plasma concentration of beta-carotene and vitamin E, hemoglobin, and hematocrit were significantly lower in patients with RA than in controls. These results provide evidence for a potential role of raised lipid peroxidation and lowered enzymic and nonenzymic antioxidants in RA because of its inflammatory character. These results suggested that OS plays a very important role

In order to protect tissues from oxidative injuries, the body possesses enzymatic

**Plasma CoQ9TOT (μmol/L) CoQ10TOT (μmol/L) αT (μmol/L) γT (μmol/L)** CO 0.328 0.023 0.031 0.004 19.9 1.13 0.643 0.051 AIA 0.468 0.044\*\* 0.027 0.003 21.6 0.72 0.834 0.060\* *Values are expressed as average standard error of mean, statistical significance (ANOVA-Tukey-Kramer post hoc*

*Concentrations of total coenzyme Q9 (CoQ9-TOT), total coenzyme Q10 (CoQ10-TOT), α-tocopherol (αT), and*

CO 43.1 3.01 1.90 0.160 23.0 1.23 0.98 0.042 AIA 32.7 2.49\* 1.63 0.187 18.7 0.829\* 1.39 0.155\* *Values are expressed as average standard error of mean, statistical significance (ANOVA-Tukey–Kramer post hoc*

*Concentrations of total coenzyme Q9 (CoQ9-TOT), total coenzyme Q10 (CoQ10-TOT), α-tocopherol (αT), and*

**CoQ10TOT (μmol/L)**

**αT (μmol/L)**

**γT (μmol/L)**

**CoQ9TOT (μmol/L)**

antioxidant enzymatic systems such as superoxide dismutases and catalase enzymes. It has been reported that AA decreases serum or synovial SOD and catalase activities together with other endogenous antioxidant systems [81]. Ramos-Romero et al. [82] showed a decrease in splenic catalase activity and, paradoxically, an increase in splenic total and mitochondrial SOD in AIA. The decreased catalase activity could be associated with the consumption of catalase in neutralizing the H2O2. On the other hand, increased splenic SOD activities could reflect the response of the body to increased ROS concentrations, and/or it could be due to the fact that arthritis was in its recovery phase 1 month after its induction. Moreover, SOD increase could also be explained by the increase in the oxidative stress found in arthritic rats and by the increased TNF-α secretion present in arthritis [82]. Both OS and TNF-α are shown to induce SOD synthesis [83]. It should be added that a similar increase in SOD activity was found in the plasma of RA patients [84] and in

changes in levels of α- and γ-tocopherol (**Table 5**).

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

in the pathogenesis of RA [80, 78].

*4.2.5 Changes in antioxidant enzymes*

*test): \*p < 0.05, \*\*p < 0.01 vs. CO.*

*γ-tocopherol (γT) in plasma.*

**Skeletal muscle mitochondria**

*test): \*p < 0.05 vs. CO.*

*γ-tocopherol (γT) in skeletal muscle mitochondria.*

**Table 4.**

**Table 5.**

**205**
