An experimental model for hydrogen peroxide-induced tissue damage. Effects of a single inflammatory mediator on...

Hydrogen peroxide is receiving increasing attention as a mediator of tissue damage during inflammation. To evaluate its destructive potential in vivo, we devised a model in which hydrogen peroxide is, initially, the sole mediator of tissue damage. Glucose oxidase, which was made cationic to obtain good retention in tissue, was injected intraarticularly in mouse knee joints. This enzyme produces hydrogen peroxide, using endogenous glucose as a substrate. The local production of hydrogen peroxide induced drastic vascular damage, as measured by 99mTc uptake and leakage of 125I-albumin. The chondrocyte proteoglycan synthesis was severely inhibited, as measured by 35SO4 incorporation. Histologic examination showed impressive inflammatory and degenerative changes, including periarticular infiltration, chondrocyte death, subchondral erosions, and muscle necrosis. Intraarticular administration of catalase could inhibit these vascular effects and cartilage damage. Systemic administration of ebselen, a synthetic glutathione peroxidase-like compound, provided partial protection. Indomethacin and piroxicam were not effective in the acute phase. We think this model is useful both for testing drugs that are purported to act as scavengers of hydrogen peroxide and for studying chronic destructive processes.