An experimental model for hydrogen peroxide induced tissue damage: effect on cartilage and other articular tissues

Hydrogen peroxide is a mediator of inflammation capable of damaging several cell types and biomolecules at relatively low concentrations in vitro. In order to evaluate the destructive potential of hydrogen peroxide in vivo, we devised an arthritis model in which hydrogen peroxide is initially the sole mediator of inflammation. Cationic glucose oxidase was injected intra-articularly into mouse knee joints. This enzyme produces hydrogen peroxide, using endogenous glucose as a substrate; thus a severe monoarthritis which lasts for several weeks can be induced. The contralateral joint is used as a control. Using histology and measurement of 99mTechnetium uptake we demonstrated severe oedema formation, damage to ligaments, muscles and cartilage, and infiltration of the tissue by inflammatory cells. These effects could be inhibited by the intraarticular administration of catalase. The effect of hydrogen peroxide on cartilage damage was shown to be reversible at low doses of glucose oxidase. This model shows what type of lesions can be induced by hydrogen peroxide generation in vivo. In addition we deem this model to be useful for studying chronic degenerative processes and for screening drugs that can scavenge hydrogen peroxide. The relevance of oxygen metabolites as inflammatory mediators is discussed.