Chronic intragastric alcohol exposure causes hypoxia and oxidative stress in the rat pancreas.
The effect of chronic enteral ethanol on pancreatic hypoxia was investigated using the hypoxia marker, pimonidazole. Male Wistar rats were fed an ethanol-containing diet for 3 weeks using an enteral model shown to cause pancreatic damage; pimonidazole (120 mg/kg i.v.) was injected 1h before sacrifice. Pimonidazole and 4-hydroxynonenal (an index of lipid peroxidation) adducts were detected immunochemically. Breathing air with low oxygen content (8% O(2)) for 1h increased pimonidazole adduct accumulation approximately 2-fold in pancreata of nai;ve rats, confirming that this technique will detect increases in hypoxia in pancreata. Pancreata of rats fed ethanol began to show signs of damage after 3 weeks. Ethanol feeding also significantly increased pimonidazole adducts in pancreas approximately 2-fold (1 or 3 weeks of ethanol produced similar values). Concomitant with increasing hypoxia in the pancreas, alcohol also caused a significant increase in 4-hydroxynonenal adducts, indicative of increased oxidative stress. These results indicate that chronic ethanol causes hypoxia at the cellular level in the pancreas in vivo; further, the data support the hypothesis that hypoxia is involved in mechanisms of chronic alcoholic pancreatitis.
McKim
Stephen E
SE
Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
Uesugi
Takehiko
T
Raleigh
James A
JA
McClain
Craig J
CJ
Arteel
Gavin E
GE
D000447:Aldehydes / Q000276:immunology / Q000378:metabolism; D000681:Amylases / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects*; D004032:Diet; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D008049:Lipase / Q000097:blood; D008297:Male; D008954:Models, Biological; D009593:Nitroimidazoles / Q000276:immunology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000447:Aldehydes; D009593:Nitroimidazoles; D000431:Ethanol; C033815:pimonidazole; D008049:Lipase; D000681:Amylases; C027576:4-hydroxy-2-nonenal