Large-dose ascorbic acid administration suppresses the development of arthritis in adjuvant-injected rats

Abstract

We performed animal experiments to test the hypothesis that active oxygen species (AOS) play a major role in adjuvant-induced arthritis in rats and to determine whether large-dose ascorbic acid administration would suppress the development of arthritis, reducing the level of damaging AOS in the same animal model. Arthritis was induced in male Lewis rats by adjuvant injection into the base of the tail. Ascorbic acid at doses of 0.5, 1.0, and 2.0 g/kg body weight (BW) was injected intraperitoneally twice each week for 3 weeks (9 rats per group). The BW, hind paw edema, and arthritis score of the extremities were monitored during the period. On day 21, synovial tissues obtained from the ankle joints were examined histologically and for the activity of superoxide dismutase (SOD). The SOD activity in the red blood cells (RBC) was also measured. The arthritic control rats showed significant increases in paw volume and arthritis score from day 11. These changes were dose-dependently reduced by ascorbic acid administration. The infiltration of inflammatory cells into the synovial tissues was markedly decreased by ascorbic acid. The increases in SOD activities produced by the adjuvant injection were significantly reduced in both the synovium and the RBC at ascorbic acid doses of 1.0 and 2.0 g/kg BW. In conclusion, large-dose ascorbic acid administration reduced the increases in hind paw inflammatory edema, arthritis in the extremities, and infiltration of the inflammatory cells into the synovial tissue in the adjuvant-induced arthritis rats. Since these anti-arthritic effects were associated with a decrease in SOD activities in both the synovium and RBC, the decrease in SOD activity could be one of the mechanisms underlying the suppressive effects of large-dose ascorbic acid on the development of arthritis in this animal model, inhibiting the damaging AOS.