Antiinflammatory effects of free radical scavengers and antioxidants: further support for proinflammatory roles of endogenous hydrogen peroxide and lipid peroxides.

Scavengers of reactive oxygen species were tested by local administration during granulomatous inflammation in the rat, induced by the subdermal implantation of carrageenin-soaked sponges. Drugs were administered either in a single dose immediately after sponge implantation, or in daily doses on days 3-6 of inflammation. The effects of the injected drugs were assessed using the day 7 granuloma. When given at the moment of sponge implantation, catalase showed antiinflammatory effects, whereas superoxide dismutase did not. However, the addition of superoxide dismutase to catalase, prior to injection, markedly potentiated the inhibition of granuloma formation by catalase alone. Negative results obtained with scavengers of hydroxyl radicals and singlet molecular oxygen suggest that protection of superoxide dismutase by catalase from inactivation by hydrogen peroxide, is a likely explanation for the observed potentiation. When administered at the moment of the induction of inflammation, alpha-tocopherol and propyl gallate, both antioxidants, also inhibited granuloma formation. All drugs tested were either ineffective or even enhanced granuloma weight following administration into a preformed granuloma. An inhibitor of both pathways of arachidonate metabolism, phenidone, inhibited granuloma formation irrespective of the moment of administration. The results presented in this paper suggest proinflammatory roles for hydrogen peroxide and lipid peroxides and a possible involvement of hydroxyl radicals and singlet oxygen in the breakdown of collagen.