Chondrocyte antioxidant defences: The roles of catalase and glutathione peroxidase in protection against H2O2 dependent inhibition of proteoglycan biosynthesis

The production of hydrogen peroxide by polymorphonuclear cells is suspected as being a cause of cellular damage during acute inflammation. In our study, the kinetics by which hydrogen peroxide suppressed proteoglycan synthesis in cartilage explant cultures suggested that the damage occurred at the level of core protein synthesis. Chondrocytes were also shown to contain both catalase and the glutathione peroxidase/reductase systems, which were both involved in the removal of 10^-4M H₂O₂. Interruption of either of these peroxide metabolizing systems markedly sensitized cartilage to a greater inhibition of synthesis by H₂O₂. Inhibition of catalase (with 3-amino 1,2,4 triazole or azide) was found to depress synthesis further, possibly because of exposure to higher steady state levels of H₂O₂. Inhibition of glutathione reductase (with 1,3-bis-(chloroethyl)-1-nitrosurea) did not expose tissue to higher steady state levels of H₂O₂, but this treatment decreased the intrachondrocyte level of reduced glutathione which may explain the increased damage obtained in the presence of H₂O₂. These results support the concept that effective H₂O₂ metabolizing systems are important in the maintenance of normal biosynthetic rates in cartilage during inflammation.