Role of hydrogen peroxide in the cytotoxicity of the xanthine/xanthine oxidase system

Abstract

1. The survival of mammalian epithelial cells exposed in vitro to the xanthine/xanthine oxidase system in phosphate-buffered saline (PBS) or serum-containing medium (SCMEM) was investigated. 2. The cytotoxic effect observed depended on the composition of the medium in which the enzymic reaction was carried out; a surviving fraction of 5 x 10(-5) was found for cells exposed in PBS and 5.2 x 10(-1) for those in SCMEM. 3. The cytotoxic product(s) formed by the xanthine/xanthine oxidase system was relatively stable in PBS; survival of cells incubated after completion of the enzymic reaction was always less than that found for cells exposed during the reaction in the same system. 4. Superoxide dismutase or mannitol present during the enzymic reaction did not inhibit the cytotoxic effect. 5. NaN3 (a single-oxygen quencher and a catalase inhibitor) added to the system in SCMEM caused a reduction in survival to the level observed for cells exposed to the enzymic reaction in PBS. 6. Catalase completely protected cells, but no protection was observed when both catalase and NaN3 were present in the reaction mixture. 7. A similar cytotoxic effect was produced when cells were treated with H2O2 alone. 8. The rate of H2O2 decomposition in medium was accelerated by the presence of serum, but this was completely inhibited by NaN3. 9. It is concluded that H2O2 is the major cytotoxic product formed by the xanthine/xanthine oxidase system.

Uric acid as a modulator of glucose and lipid metabolism

“…During oxygen-dependent reactions, this enzyme generates ROS, such as superoxide anion and hydrogen peroxide [65,69]. Thus, the reduction of uric acid using allopurinol or febuxostat also decreases ROS generation, making it difficult to interpret these findings.…”

Antioxidant and redox status after maximal aerobic exercise at high altitude in acclimatized lowlanders and native highlanders

“…It indicates that dismutation of superoxide radicals by SOD is not a sole source of H 2 O 2 in HAN. One of the predominant sources of H 2 O 2 is xanthine/xanthine oxidase system (Fatokun et al 2007;Link and Riley 1998). An almost 50% increase in UA level in HAN after exercise further supports the hypothesis that in case of HAN the generation of H 2 O 2 is predominantly through xanthine/xanthine oxidase system which acts as a substrate for GPX.…”

Cellular mechanism of U78517F in the protection of porcine coronary artery endothelial cells from oxygen radical‐induced damage

“…H202 acts directly on cells with consequent damage of cells (Sacks et al, 1978;Weiss et al, 1981;Harlan et al, 1984). Link & Riley (1988) suggested in mammalian epithelial cells that H202, a stable product in the system investigated, is responsible for the death of cells after the exposure to X/XO system. As H202 can readily pass through cell membranes, it interacts with intracellular iron to form highly reactive oxidants such as the hydroxyl radical (Grisham & Granger, 1988).…”