The role of cationized catalase and cationized glucose oxidase in mucosal oxidative damage induced in the rat jejunum.
The successful prevention of hydrogen peroxide-induced damage to the rat jejunal mucosa by cationized catalase is described in this study. Biological damage was induced in a closed circulating intestinal loop of the rat by hydrogen peroxide and by hydroxyl radicals induced in situ via the metal-mediated Haber-Wiess reaction. The mucosal activity of lactate dehydrogenase and the amount of potassium ions were used to quantitatively characterize the tissue damage. Catalase was cationized by reacting it with N,N'-dimethyl-1,3-propanediamine to give a soluble product or with polyhistidine to give an insoluble product. The activity of the modified enzymes was assessed, and their ability to protect the rat jejunal mucosa against oxidative stress was studied. It was found that in all cases the cationized enzymes were superior to the native catalase in their shield capability. A significant protection against Fe(II)/H2O2 and ascorbic acid/copper ion-mediated damage was obtained when the cationized enzymes were used. In the presence of glucose, native glucose oxidase failed to cause damage in the rat jejunal mucosa; however, the cationized enzyme caused profound tissue injury. These findings indicate the potential therapeutic merit of cationized enzymes for the treatment of pathological processes in the intestine, whenever oxidative stress is involved.
Kohen
R
R
School of Pharmacy, Hebrew University of Jerusalem, Israel.
Kakunda
A
A
Rubinstein
A
A
D000818:Animals; D002374:Catalase / Q000627:therapeutic use*; D002412:Cations; D005609:Free Radicals; D005949:Glucose Oxidase / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D007413:Intestinal Mucosa / Q000201:enzymology; D007579:Jejunal Diseases / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D011188:Potassium / Q000378:metabolism; D051381:Rats
D002412:Cations; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005949:Glucose Oxidase; D002374:Catalase; D011188:Potassium