A. Sakai et al., Large-dose ascorbic acid administration suppresses the development of arthritis in adjuvant-injected rats, ARCH ORTHOP, 119(3-4), 1999, pp. 121-126
We performed animal experiments to test the hypothesis that active oxygen s
pecies (AOS) play a major role in adjuvant-induced arthritis in rats and to
determine whether large-dose ascorbic acid administration would suppress t
he development of arthritis, reducing the level of damaging AOS in the same
animal model. Arthritis was induced in male Lewis rats by adjuvant injecti
on 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 w
eeks (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 act
ivity of superoxide dismutase (SOD). The SOD activity in the red blood cell
s (RBC) was also measured. The arthritic control rats showed significant in
creases in paw volume and arthritis score from day 11. These changes were d
ose-dependently reduced by ascorbic acid administration. The infiltration o
f inflammatory cells into the synovial tissues was markedly decreased by as
corbic acid. The increases in SOD activities produced by the adjuvant injec
tion were significantly reduced in both the synovium and the RBC at ascorbi
c acid doses of 1.0 and 2.0 g/kg BW. In conclusion, large-dose ascorbic aci
d administration reduced the increases in hind paw inflammatory edema, arth
ritis in the extremities, and infiltration of the inflammatory cells into t
he synovial tissue in the adjuvant-induced arthritis rats. Since these anti
-arthritic effects were associated with a decrease in SOD activities in bot
h the synovium and RBC, the decrease in SOD activity could be one of the me
chanisms underlying the suppressive effects of large-dose ascorbic acid on
the development of arthritis in this animal model, inhibiting the damaging
AOS.