Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/10442
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Type: Journal article
Title: Nitric oxide effect on colonocyte metabolism: co-action of sulfides and peroxide
Author: Roediger, W.
Babidge, W.
Citation: Molecular and Cellular Biochemistry: an international journal for chemical biology in health and disease, 2000; 206(1-2):159-167
Publisher: Kluwer Academic Publ
Issue Date: 2000
ISSN: 0300-8177
1573-4919
Abstract: Luminal levels of nitric oxide/nitrite are high in colitis. Whether nitric oxide is injurious or protective to human colonocytes is unknown and the role of nitric oxide in the genesis of colitis unclear. The aims were to establish whether nitric oxide was injurious to oxidation of substrates (n-butyrate and D-glucose) in isolated human and rat colonocytes both alone and in the presence of hydrogen sulfide and hydrogen peroxide, agents implicated in cell damage of colitis. Nitric oxide generation from S-nitrosoglutathione was measured by nitrite appearance. Colonocytes were isolated and incubated with [1-14C] butyrate or [6-14C] glucose and 2.6 microM nitric oxide, 1.5 mM sodium hydrogen sulfide or 2.5 mM hydrogen peroxide. Acyl-CoA esters were measured by high performance liquid chromatography, 14CO2 radiochemically and lactate/ketones by enzymic methods. Results indicate that nitric oxide very significantly (p < .001) reduced acyl-CoA formation but did not impair 14CO2 generation. Peroxide and sulfide with nitric oxide resulted in significant reduction (p < 0.01) of substrate oxidation to CO2. Sulfide significantly stimulated release of nitric oxide from S-nitrosoglutathione. The principal conclusion is that nitric oxide diminishes CoA metabolism in colonocytes. CoA depletion has been observed in chronic human colitis for which a biochemical explanation has been lacking. For acute injurious action in human colonocytes nitric oxide requires co-action of peroxide and sulfide to impair oxidation of substrates in cells. From current observations treatment of colitis should aim to reduce simultaneously nitric oxide, peroxide and sulfide generation in the colon.
Keywords: Colon
Epithelial Cells
Animals
Humans
Rats
Rats, Sprague-Dawley
Hydrogen Sulfide
Hydrogen Peroxide
Nitric Oxide
Butyrates
Nitroso Compounds
S-Nitrosoglutathione
Acetyl Coenzyme A
Glucose
Glutathione
Drug Combinations
Free Radical Scavengers
Chromatography, High Pressure Liquid
Oxidation-Reduction
DOI: 10.1023/a:1007034417320
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Surgery publications

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