Effect of oxygen‐derived free radicals on hyaluronic acid

To investigate possible mechanisms of hyaluronic acid depolymerization, superoxide anion and other secondary oxygen-derived free radicals were generated in vitro and allowed to act upon a hyaluronate substrate. Superoxide, generated either enzymatically with xanthine oxidase or by stimulation of polymorphonuclear leukocytes, reduced the viscosity of hyaluronate solutions dramatically while the chromatographic profiles of the glycosaminoglycan shifted toward lower molecular weights. Superoxide-treated hyaluronate also became susceptible to further degradation by beta-N-acetylglucosaminidase A. Experiments with scavengers of various toxic oxygen-derived free radicals clearly implicated these reactants as mediators of hyaluronate depolymerization. Generation of superoxide by leukocytes in vivo may account for the loss of synovial fluid viscosity that accompanies inflammatory joint disease.