title: Hyaluronan peroxidation is required for normal synovial function: an hypothesis.
abstract: Despite widespread use of antioxidants, reactive oxygen species have important functions in normal tissues. Herein, we present an example of a physiological role for free radicals, and in particular, reactive oxygen species, that are suppressed by anti-oxidants. Free radicals catalyze the degradation of hyaluronan in synovial fluid, a tissue in which hyaluronidase activity is barely detectable. Articular cartilage requires a low oxygen environment. The process of hyaluronan peroxidation consumes significant amounts of molecular oxygen, thus keeping the tension of oxygen in the joint at a low but physiologically critical level. One concern is the change in physical activity between day and night, with periods of joint hyperemia and ischemia, respectively. Increased oxygen and the resulting oxidative stress would lead to chondrocyte dysfunction and cartilage damage. A mechanism for keeping oxygen levels low is required. We postulate that a mechanism indeed exists for the removal of excess oxygen. High-molar-mass hyaluronan turnover in synovial fluid utilizes peroxidative degradation, during which oxygen is massively consumed. The peroxidation itself may be initiated by hydrogen peroxide, which is produced by chondrocyte mitochondria, that can diffuse into the synovial fluid. The resulting decrease in available oxygen down-regulates hyaluronan peroxidation. This in turn prevents excessive oxygen consumption. It appears that free radicals and reactive oxygen species may be components of normal physiology, particularly in the synovial fluid of joints and articular cartilage. It is suggested therefore that indiscriminate use of anti-oxidants, vigorously promoted currently by health professionals and the health industry, be approached with caution.
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska Cesta 9, SK-84104 Bratislava, Slovakia.
authors.forename: I
authors.initials: I
authors.lastname: Juranek
authors.affiliation: Department of Basic Biomedical Sciences, Touro College of Osteopathic Medicine, 230 West-125th St., New York, NY 10027, USA. Electronic address: robert.stern@ucsf.edu.
authors.forename: R
authors.initials: R
authors.lastname: Stern
authors.affiliation: Institute of Experimental Pharmacology and Toxicology, Slovak Academy of Sciences, Dubravska Cesta 9, SK-84104 Bratislava, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Soltes
mesh_terms: D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007596:Joints / Q000502:physiology*; D008954:Models, Biological; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D006820:Hyaluronic Acid; D006861:Hydrogen Peroxide