Effect of Anti - inflammatory Drugs on the Degradation of Hyaluronate and Collagen by Reactive Oxygen Species

Lee, Eun Woo; Lee, Sun Ho; Yim, Hyun; Lee, Kwang Soo; Chung, Myung Hee

Abstract

Leukocytes, when subjected to phagocytic, immunologic or chemical stimuli, are known to exhibit a sequence of morphological and biochemical events which lead to the production of Hâ‚‚, Oâ‚‚, Oâ‚‚â», and even OH as well as the secretion of various lysosomal lytic enzymes into the extracellular environments. It was been proposed that some antiinflammatory drugs may exert their therapeutic effects by inhibiting the production of reactive oxygen species or by abrogating the effects of reactive oxygen species ontissue components. In the present study, effects of various quenchers and antiinflammatory drugs were observed on the changes of viscosity of hyaluronate and collagen gelation by oxygen radicals generated by xanthine and xanthine oxidase. Quenching effects of antiinflammatory drugs on reactive oxygen species were also observed with gas chromatography. 1. Decrease of viscosity of hyaluronate and inhibition of collagen gelation by xanthine and xanthine oxidase were inhibited by various quenchers. 2. Several oxygen radical quenchers and antiinflammatory drugs did not affect viscosity of hyaluronate and collagen gelation. 3. Reactive ouygen species generated by xanthine and xanthine oxidase affected both viscosity of hyaluronate and collagen gelation with similar pattem. Therefore, in this study quenching effects of antiinflammatory drugs on reactive oxygen species have been examined by observing viscosity changes of hyaluronate. Sodium salicylate, acetylsalicylic acid, indomethacin and hydrocortisone affected viscosity changes of hyalumnate by xanthine and xanthine oxidase. The pattem of inhibition of hyaluronate degradation by these drugs were comparable to the inhibition produced by OH scavengers and singlet oxygen quencher. 4. To danonstrate the generation of OH ethylene was determined from methional incubated with xanthine and xanthine oxidase according to gas chromatography method. Xanthine and xanthine oxidase produced ethylene fmm methional and the production was inhibited by antiinflammatory drugs. The result obtained in this study suggest that action of antiinflammatory drugs may, to some event, be attributed to their ability to intercept reactive oxygen species in addition to inhibition of synthesis of prostaglandin.