title: Chronic intragastric alcohol exposure causes hypoxia and oxidative stress in the rat pancreas.
abstract: 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.
authors.affiliation: Laboratory of Hepatobiology and Toxicology, Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: McKim
authors.forename: Takehiko
authors.initials: T
authors.lastname: Uesugi
authors.forename: James A
authors.initials: JA
authors.lastname: Raleigh
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Arteel
mesh_terms: 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
chemical_list: D000447:Aldehydes; D009593:Nitroimidazoles; D000431:Ethanol; C033815:pimonidazole; D008049:Lipase; D000681:Amylases; C027576:4-hydroxy-2-nonenal