Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model

Nevzat GÖZEL1, Maşallah ÇAKIRER1, Ahmet KARATAŞ2, Mehmet TUZCU3, Fethi Ahmet ÖZDEMİR4, Adile Ferda DAĞLI5, Kazım ŞAHİN6, Süleyman Serdar KOCA2

1Department of Internal Medicine, Medical Faculty of Fırat University, Elazığ, Turkey
2Department of Rheumatology, Medical Faculty of Fırat University, Elazığ, Turkey
3Department of Medical Biology, Medical Faculty of Fırat University, Elazığ, Turkey
4Department of Molecular Biology and Genetics, Bingöl University, Bingöl, Turkey
5Department of Pathology, Medical Faculty of Fırat University, Elazığ, Turkey
6Department of Animal Nutrition, Medical Faculty of Fırat University, Elazığ, Turkey

Keywords: Collagen-induced arthritis; rheumatoid arthritis; sorafenib

Abstract

Objectives: This study aims to examine the effects of sorafenib on a collagen-induced arthritis model.
Materials and methods: The study included 50 randomly selected female Wistar-albino rats (8-10-week-old, weighing between 200 g to 250 g). The rats were divided into five equal groups as control, arthritis, etanercept, sorafenib high-dose, and sorafenib low-dose groups, respectively. Arthritis was induced by injecting mixed intradermal chicken type II collagen and incomplete Freund's adjuvant. Twenty-four hours after the advent of arthritis; rats in group 3 were injected subcutaneous etanercept (6 mg/kg/week), while those in groups 4 and 5 were given sorafenib (10 or 30 mg/ kg/day) orally until they were sacrificed on the 34th day. The rat claws and trunk bloods were carefully examined to note perisynovial inflammation and cartilage/bone injury through histopathology. Tissue vascular endothelial growth factor (VEGF) and VEGF receptor levels were carefully checked using western blot analysis.
Results: Analysis of the experimental data showed that collagen-induced arthritis decreased in treatments groups after 12-13 days and 34th day in contrast with the arthritis group. Histopathological examination revealed broad perisynovial inflammation and cartilage/bone break down in the arthritis group. Compared to the control group, tissue VEGF and VEGF receptor levels increased in the arthritis group. Sorafenib and etanercept decreased tissue VEGF and VEGF receptor levels, perisynovial inflammation, damage of cartilage/bone.
Conclusion: Our findings indicate that sorafenib treatment ameliorates collagen-induced arthritis with anti-VEGF effectiveness.

Citation: Gözel N, Çakırer M, Karataş A, Tuzcu M, Özdemir FA, Dağlı AF, et al. Sorafenib Reveals Anti-Arthritic Potentials in Collagen Induced Experimental Arthritis Model. Arch Rheumatol 2018;33(3):309-315

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This study was supported by Firat University Scientific Research Projects Coordination Unit (FUBAP).