role of oxygen-free radicals on the motility of rat ileum effects of xanthine plus xanthine oxidase

the major objective of the present study was to characterize the effects of oxidants generated b xanthine (x) plus xanthine oxidase (xo) on isolated rat ileum motility. the effects of three concentrations of x/xo on the basal tone of the rat ileum preparation were studied for 20 minutes. developed tensions were measured in mg/mg tissues and then expressed as percentage of baseline tension. also the effects of 2x concentration of x/xo in the presence and absence of superoxide dismutase, catalase, mannital, histidine, and deferoxamine were evaluate. the results were expressed as mean ± se. xanthine puls xanthine exidase produced relaxation of ileum. superoxide dismutase (a superoxide anion metabolizer) and catalase (a hydrogen peroxide scavenger) did not protect ileum from effects of x/xo suggesting that neither superoxide anion nor hydrogen peroxide involse in x/xo- induced relaxation of ileum. the results of this study suggest that hydrogen peroxide formed extracelluarly by x/xo may enter the cells and interact with intracellular iron of form a highly reactive oxidant. hydroxyl radical. the finding that two powerful hydroxyl radical scavengers, dimethylthiourea (dmtu) and mannitol offered protection against x/xo-induced relaxation of ileum suggest formation of hydroxyl radical withing the cells. pretreatment with deferoxamin, a potents iron chelator, reduced the relaxation of ileum, indicating that hydroxyl radical plays an important role in mediating the x/xo –induced relaxation of ileum. in addition.the ability of exogenously administered histidine to reduce relaxation suggests that singlet oxyen is another oxygen derivative which is responsible for relaxation of ileum-induced by x/xo.