Oxygen free radicals and modulation of ileum smooth muscle tone
The results of this study indicate that exogenously-generated oxy-radicals produce relaxation, contraction or contraction/relaxation of rat ileum depending upon the generating system. Xanthine (X) plus xanthine oxidase (XO) produced relaxation of ileum. The relaxation was attenuated by the hydroxyl radical scavengers mannitol and dimethylthiourea (DMTU); and the singlet oxygen scavenger, histidine, supporting the idea that the hydroxyl radical (.OH) and singlet oxygen are involved in X/XO-induced relaxation of ileum. Deferoxamine, an iron chelator, reduced the relaxation of the ileum, indicating that .OH mediates the X/XO-induced relaxation of ileum. Xanthine/xanthine oxidase-induced relaxation is partly mediated through cyclooxygenase metabolites, and partly through nitric oxide and ATP-sensitive potassium channels. Hydrogen peroxide (H2O2) produced a biphasic response (an initial contraction followed by relaxation), which appeared to be due to the generation of .OH. The contraction/relaxation induced by H2O2 is mediated through cyclooxygenase metabolites. The hydrogen peroxide-evoked biphasic response in rat ileum is not mediated through nitric oxide, acetylcholine or histamine. Dihydroxy fumaric acid (DHF) plus ferric chloride (FeCl 3) and adenosine diphosphate (ADP) produced concentration-dependent contraction of ileum. Mannitol, DMTU, and histidine partially inhibited the DHF/FeCl3-ADP-induced contraction, supporting the idea that hydroxyl radicals and singlet oxygen are involved in DHF/FeCl3-ADP-induced contraction of ileum. DHF/FeCl3-ADP-induced contraction is mediated partly through arachidonic acid metabolites and histamine. These results suggest that oxygen radicals play a role in the motility of ileum.
Doctor of Philosophy (Ph.D.)