**6. Conclusion**

amino acids such as arginine, lysine, threonine, and proline [107]. Moreover, carbonylation of proteins that are part of the contractile apparatus could be crucial in RC muscle dysfunction. Fedorova et al. [108] showed that carbonylation of actin could very much affect actomyosin ATPase activity, thus promoting subsequent muscle atrophy. Taken together, action of pro-inflammatory cytokines, mitochondrial dysfunction, and enhanced activity NADPH oxidase and xanthine oxidase

tion of these factors consequently leads to imbalance in protein synthesis and

Decreased physical activity results in downregulation of antioxidants. Combina-

Rheumatoid cachexia still remains a poorly investigated disease, and many scientists are trying to understand the exact mechanism by which the disease takes place. Several animal models of RA are used in the study of this condition. The best studied animal model to date has been CIA, which, by its characteristics, offers the most accurate comparison with humans, as the onset of this affection is relatively slow and the immune mechanisms driving the onset of cachexia are closest to

Recently, Albarse et al. [110] have been investigating the development of cachexia in CIA in DBA1/J mice. In their study, they have observed significant increase in free exploratory locomotion as well as grip strength and endurance exercise performance. Additionally, they registered reduction of muscle weight in several muscles, which could indicate that mechanisms, which led to the onset of

Another model of rheumatoid arthritis and adjuvant arthritis was also used to investigate muscle wasting in male and female Lewis rats in the study of Roubenoff et al. [111]. It was shown that adjuvant-induced rats also manifested severe muscle loss when compared to control as well as pair-fed groups. This makes adjuvant arthritis suitable model for study of cachexia in chronic inflammatory diseases. Even though there have been multiple authors dedicated to unraveling the true cause of rheumatoid-induced cachexia, much more study is needed in order to

*Mechanism of the effect of oxidative stress on the onset of cachexia in rheumatoid arthritis. NOX, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; XO, xanthine oxidase; ROS, reactive oxygen species; RNS,*

arthritis, could subsequently promote muscle atrophy and weakness.

contribute to the overproduction of ROS/RNS.

*Animal Models in Medicine and Biology*

**5.1 Animal models in rheumatoid cachexia**

rheumatoid cachexia in people [109].

**Figure 4.**

**208**

*reactive nitrogen species.*

degradation resulting in muscle wasting (**Figure 4**).

The animal model adjuvant arthritis gives a broad spectrum of possibilities to study different pathological mechanism of rheumatoid arthritis. One important pathological pathway is the connection between inflammation and oxidative stress, which is studied on both systemic and local levels. From our original results as well as from results reported by other authors, it is evident that treatment with compounds possessing redox balance modulating properties might be of great relevance for new strategies for therapy of rheumatoid arthritis. For this purpose, adjuvant arthritis seems to be an ideal animal model. Moreover, this animal model has also a good potential in the research of inflammatory cachexia and its pharmacological intervention.

## **Acknowledgements**

Our experimental studies were supported by grants: APVV-15-0308, APVV SK-PT-18-0022, and VEGA 2/0115/19. We thank Martin Chrastina, MSc, for technical assistance.
