Hydrogen peroxide-mediated cytotoxicity to cultured colonic epithelial cells.
Reactive oxygen metabolites (ROM) contribute to colonic cellular injury, in certain pathophysiological conditions. We investigated the role of iron and individual metabolites in their cytotoxicity to cultured colonic epithelial cells from adult white rabbits. Reactive oxygen metabolites, enzymatically generated by hypoxanthine/xanthine oxidase, have a direct cytotoxic effect on cultured colonic epithelial cells. This cellular injury was inhibited by catalase but not SOD. Damage was not aggravated by ferrous iron or EDTA-chelated iron. Such damage was prevented by chelating intracellular iron, but not extracellular iron. These results suggest that H2O2 is more toxic to colonic epithelial cells than 02.- and OH. in the extracellular space. H2O2 enter the intracellular space and is converted to the more reactive and harmful OH. leading to cellular injury in the presence of intracellular iron.
Hata
Y
Y
Department of Gastroenterology, Department of Veterans Affairs Medical Center, Long Beach, California 90822, USA.
Kawabe
T
T
Hiraishi
H
H
Ota
S
S
Terano
A
A
Ivey
K J
KJ
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology*; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D005296:Ferrous Compounds; D005609:Free Radicals; D016877:Oxidants; D017382:Reactive Oxygen Species; D004492:Edetic Acid; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D003676:Deferoxamine