Treatment of Collagen-Induced Arthritis of Rats with Water-Soluble Fullerene (C60)

Abstract

Several lines of evidence suggest a role for oxidative stress in the pathogenesis of rheumatoid arthritis (RA) Repetitive cycles of hypoxia and reoxygenation within arthritic joints can generate reactive oxygen species (ROS) ROS can function as a second messenger to activate nuclear factor kappa-B which orchestrates the expression of a spectrum of genes involved in the inflammatory responses In this study we investigated the potential therapeutic effect of a free-radical scavenger water-soluble fullerene (C60) on collagen-induced arthritis (CIA) of rats an experimental animal model of human RA Male Sprague-Dawley rats were immunized by two intradermal injections one week apart with bovine type II collagen emulsified in Freund’s adjuvant The water-soluble C60 or phosphate buffered saline (PBS) was administered by intraarticular injection into ankle joints of rats on day 7 after the first immunization The response to treatments was determined by measuring the articular index and radiographic and histological scores Levels of interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF) in homogenate extracts of ankle joints were analyzed Microvessel numbers in the arthritic joints were also measured after immunohistochemical staining Significant reduction in articular index was observed in C60-treated rats as compared with their control counterparts C60 injection significantly ameliorated radiological and histological scores in ankle joints as well There were significantly reduced concentrations of IL-1β but not VEGF in homogenate extracts of ankle joints Marked decreased microvessel numbers were observed in the ankle joints of C60-treated rats as compared with PBS-injected animals In conclusion this study demonstrates that intraarticular administration of C60 ameliorates CIA of rats through anti-inflammatory and anti-angiogenic mechanisms

Date of Award	2014 Sept 2
Original language	English
Supervisor	Chrong-Reen Wang (Supervisor) & Ai-Li Shiau (Supervisor)