Increased microsomal oxidation of hydroxyl radical scavenging agents and ethanol after chronic consumption of ethanol

https://doi.org/10.1016/0003-9861(83)90606-9Get rights and content

Abstract

The oxidation of ethanol by rat liver microsomes is increased after chronic ethanol consumption. Previous experiments indicated that hydroxyl radicals play a role in the mechanism whereby microsomes oxidize ethanol. Experiments were therefore carried out to evaluate the role of these radicals in ethanol oxidation by microsomes from ethanol-fed rats, and to determine whether the increase in ethanol oxidation by these induced microsomes correlates with an increase in the generation of hydroxyl radicals. Rat liver microsomes from ethanol-fed rats catalyzed the oxidation of two typical hydroxyl radical scavenging agents, dimethylsulfoxide and 2-keto-4-thiomethylbutyric acid, at rates which were two- to threefold greater than rates found with control microsomes. This increased rate of oxidation of hydroxyl radical scavengers was similar to the increased rate of microsomal oxidation of ethanol. Azide, which inhibits contaminating catalase in microsomes, increased the oxidation of dimethyl sulfoxide and 2-keto-4-thiomethylbutyric acid by both microsomal preparations. This suggests that H2O2 may serve as the microsomal precursor of the hydroxyl radical. Cross competition for oxidation between ethanol and the hydroxyl radical scavenging agents was observed. Moreover, the oxidation of ethanol, dimethyl sulfoxide, or 2-keto-4-thiomethylbutyric acid was inhibited by other compounds which interact with hydroxyl radicals, e.g., benzoate, and the free-radical, spin-trapping agent, 5,5-dimethyl-1-pyrroline-N-oxide. These results suggest that the increase in the rate of ethanol oxidation found with microsomes from ethanol-fed rats may be due, at least in part, to an increase in the rate of production of hydroxyl radicals by these induced microsomes. Increased production of oxyradicals may possibly result in oxidative damage to the liver cell as a result of ethanol consumption.

References (45)

  • C.S. Lieber et al.

    Biochem. Biophys. Res. Commun

    (1970)
  • A.I. Cederbaum et al.

    Biochem. Pharmacol

    (1981)
  • A.I. Cederbaum et al.

    Biochem. Biophys. Res. Commun

    (1980)
  • R. Teschke et al.

    Arch. Biochem. Biophys

    (1974)
  • R. Teschke et al.

    J. Biol. Chem

    (1975)
  • D.R. Koop et al.

    J. Biol. Chem

    (1982)
  • K. Ohnishi et al.

    J. Biol. Chem

    (1977)
  • G.T. Miwa et al.

    Arch. Biochem. Biophys

    (1978)
  • G. Cohen et al.

    Arch. Biochem. Biophys

    (1980)
  • A.I. Cederbaum et al.

    Arch. Biochem. Biophys

    (1980)
  • K. Ohnishi et al.

    Arch. Biochem. Biophys

    (1978)
  • J.M. McCord et al.

    FEBS Lett

    (1978)
  • B. Halliwell

    FEBS Lett

    (1978)
  • C.S. Lieber et al.

    J. Biol. Chem

    (1970)
  • C.S. Lieber et al.

    Amer. J. Clin. Nutr

    (1970)
  • O.H. Lowry et al.

    J. Biol. Chem

    (1951)
  • S.M. Klein et al.

    FEBS Lett

    (1980)
  • C. Beauchamp et al.

    J. Biol. Chem

    (1970)
  • G. Cohen et al.

    J. Biol. Chem

    (1974)
  • C.S. Lai et al.

    Arch. Biochem. Biophys

    (1978)
  • C.A. Lai et al.

    Arch. Biochem. Biophys

    (1979)
  • A.I. Cederbaum et al.

    Biochem. Biophys. Res. Commun

    (1979)
  • Cited by (94)

    • Ferritin-dependent radical generation in rat liver homogenates

      2009, Toxicology
      Citation Excerpt :

      Rat livers were excised and homogenized for 30 s in a blender with 40 mM potassium phosphate buffer (pH 7.4). Liver microsomes were isolated as previously described (Klein et al., 1983) by differential centrifugations, utilizing a buffer containing 0.25 M sucrose–0.01 M Tris, pH 7.4. The microsomes were washed with 125 mM KCl, suspended in 125 mM KCl, and stored at −70 °C.

    • CYP2E1 and oxidative liver injury by alcohol

      2008, Free Radical Biology and Medicine
    • The Relationship between Alcohol-induced Apoptosis and Oxidative Stress in the Liver

      2005, Comprehensive Handbook of Alcohol Related Pathology
    View all citing articles on Scopus

    This work was supported by USPHS Grants AA 03312, AA 03508 (Alcohol Research Center), and Research Career Development Award 2K02-AA 00003 (A.I.C.) from the National Institute on Alcohol Abuse and Alcoholism.

    View full text