Chronic hypoxia and glutathione-dependent detoxication in rat small
intestine.
Legrand, Terry S., and Tak Yee Aw.
Department of Physiology and Biophysics, Louisiana State University
Medical Center, Shreveport, LA 71130
APStracts 2:0219G, 1995.
It has previously been found that chronic O2 deficiency decreases
activity of the enzymes of the glutathione (GSH) redox system in the
liver. To study the effects of O2 deficiency on intestinal
detoxication capacity, pair-fed (16 g food/day) Sprague-Dawley rats
were exposed to air (20.9% O2; n=4) or 10% O2 (n=4) for 10 days.
Animals were sacrificed and intestinal mucosal homogenate (20% w/v)
was obtained and assayed for activities of glucose 6-phosphate
dehydrogenase (G6PD), GSH peroxidase (GSHPx), GSSG reductase
(GSSGRd), and _-glutamyl cysteine synthetase (_-GCS). Hypoxia
decreases activities of GSHPx, GSSGRd, and _-GCS by about 50%, which
suggests compromised detoxication. A proximal to distal reduction in
enzymatic capacity indicates impairment of detoxication may be more
pronounced in the distal intestine. G6PD, a key enzyme in NADPH
production, remains unchanged. Urinary malondialdehyde was also
monitored. Hypoxic rats exhibited a 3-fold increase in thiobarbituric
acid reactive substance, consistent with a generalized oxidative
stress in these animals. Taken together, the results indicate that
chronic hypoxia promotes tissue oxidative stress and impairs the
ability of the enterocyte to metabolize ingested oxidants.
Received 10 July 1995; accepted in final form 17 October 1995.
APS Manuscript Number G285-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95