**4. Conclusion**

New treatment strategies based on blockade of cytokine pathways in late stages of RA are progressing. In spite of their benefits, long-time utilization of these blocking agents has indicated side effects. The antioxidant defense system includes endogenous (enzymatic and nonenzymatic) and exogenous (dietary) antioxidants that interact in establishing redox homeostasis in the body. Therapeutic benefits from antioxidant treatment are primarily bound to reduction of systemic OS.

CoQ10 treatment significantly improved concentrations of the investigated endogenous antioxidants (CoQ9-total, CoQ10-total, and gamma tocopherol in plasma). CoQ10 for its bioenergetic, antioxidant, and anti-inflammatory properties might be therapeutically useful for a long-term supplementary administration to patients with inflammatory diseases such as RA.

In our study, we have shown the ability of per orally administered HA to improve the antioxidant defense (SOD, GPx, and total antioxidant capacity of plasma). This therapeutic effect of HA could be a result of direct (intestinal absorption) and indirect (intestinal cell immunomodulatory) anti-inflammatory activities. Recent results have shown that dietary high-molecular-weight HA can be distributed to connective tissues. Dietary HA could be beneficial for joints, knee pain, relief of synovial effusion, or inflammation and improvement of muscular knee strength. HA also binds to toll-like receptor-4 (TLR4) in the luminal surface of the large intestine resulting in the downregulation of systemic proinflammatory cytokines.

However, further research is needed with endogenous antioxidants, mainly human studies, in order to establish an antioxidative treatment approach in inflammatory-based diseases such as RA.

## **Acknowledgements**

The experiments were supported by APVV-15-0308, VEGA 2/0044/15, and VEGA 2/0115/19. In the experiment realization, Danica Mihalova, Jana Urgosova, Frantisek Drafi, Martina Horvathova, Kristina Farkasova, Anna Gvozdjakova, Olga Vancova, and Olga Ulicna were involved. Hyaluronan samples were purchased by cofounder and current CEO Vladimir Velebny (Contipro, Czech Republic). Thanks to Miloslav Zloh for the technical assistance in manuscript preparation.

**165**

**Author details**

Karol Svik1

provided the original work is properly cited.

Katarina Bauerova1,2,\*, Jarmila Kucharska3

, Vladimir Jakus3

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

and Jana Muchova3

Medicine, Slovak Academy of Sciences, Bratislava, Slovakia

2 Faculty of Pharmacy, Comenius University, Bratislava, Slovakia

3 Faculty of Medicine, Comenius University, Bratislava, Slovakia

\*Address all correspondence to: katarina.bauerova@savba.sk

1 Institute of Experimental Pharmacology and Toxicology, Centre of Experimental

, Silvester Ponist1

, Lukas Slovak1

,

*The Role of Endogenous Antioxidants in the Treatment of Experimental Arthritis*

*DOI: http://dx.doi.org/10.5772/intechopen.85568*
