These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Ethanol-derived immunoreactive species formed by free radical mechanisms.
    Author: Moncada C, Torres V, Varghese G, Albano E, Israel Y.
    Journal: Mol Pharmacol; 1994 Oct; 46(4):786-91. PubMed ID: 7969061.
    Abstract:
    Recent studies have shown that the alpha-hydroxyethyl radical (CH3CHOH), a metabolite of ethanol, is produced in vitro and in vivo. We report studies that establish the immunogenicity of alpha-hydroxyethyl radical-derived protein adducts. Rat liver microsomes incubated in the presence of [14C]ethanol and NADPH (under aerobic conditions) incorporate 14C into acid-stable adducts. Incorporation was markedly inhibited by the free-radical scavenger alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone. Rabbits immunized with rat liver microsomes that had been preincubated with ethanol and NADPH generated antibodies that recognized polylysine-acetaldehyde adducts and adducts formed by incubation of proteins with an alpha-hydroxyethyl radical-generating system (ethanol plus H2O2 plus Fe2+). Rabbits immunized with microsomes that had been preincubated with ethanol and NADPH plus alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone generated antibodies that recognized polylysine-acetaldehyde adducts. However, their reactivity against alpha-hydroxyethyl-derived protein epitopes was greatly reduced or was virtually abolished. Data indicate that microsomes metabolizing ethanol generate two types of adducts, acetaldehyde-derived adducts and alpha-hydroxyethyl radical-derived adducts, both of which are immunogenic. Immunization of rabbits with alpha-hydroxyethyl-bovine serum albumin adducts led to the production of antibodies that recognized alpha-hydroxyethyl-rabbit serum albumin adducts but did not recognize the native protein. Chronic alcohol feeding of rats led to the production of antibodies that recognized alpha-hydroxyethyl-rat serum albumin adducts but did not recognize rat serum albumin. The study (i) indicates that alpha-hydroxyethyl radical-derived protein adducts are immunogenic, (ii) supports earlier work that proposed that alpha-hydroxyethyl radicals generated in different systems bind covalently to proteins, and (iii) demonstrates the formation of antibodies to alpha-hydroxyethyl-derived protein adducts after chronic alcohol ingestion in vivo. The findings may have implications in the identification of chronic alcohol abuse and the pathogenesis of alcohol-induced organ damage.
    [Abstract] [Full Text] [Related] [New Search]