TY - JOUR
T1 - A correlation between hydroxyl radical generation and ethanol oxidation by liver, lung and kidney microsomes
AU - Winston, Gary W.
AU - Cederbaum, Arthur I.
N1 - Funding Information:
* These studies were supported by USPHS Grants AA03312 and AA04413 and by Research Career Devel-oument Award 5KO2-AA-00003 from the National Institute on 1 Alcohol Abuse and Alcoholism. t Send correspondence to: Dr. A. I. Cederbaum, Department of Biochemistry, Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029 U.S.A. $ Abbreviations used: KTBA, 2-keto-rt-thiomethyl-butyric acid; MezSO, dimethylsulfoxide; ‘OH, hydroxyl radical or a species with the oxidizing power of the hydroxyl radical.
PY - 1982/6/1
Y1 - 1982/6/1
N2 - A comparison of the abilities of microsomes from liver, kidney and lung to oxidize ethanol and to generate hydroxyl radicals was conducted to determine if these two variables correlated with one another. The oxidation of 2-keto-4-thiomethylbutyric acid (KTBA) to ethylene, and the production of formaldehyde from dimethylsulfoxide (Mc2SO), served as chemical probes for the detection of the production of hydroxyl radicals by the microsomes. Liver microsomes oxidized ethanol at rates several-fold greater than those found with lung and kidney microsomes. This greater rate of ethanol oxidation by liver microsomes correlated with a greater rate of oxidation of the hydroxyl radical scavengers by the liver microsomes (liver > lung ≈ kidney). In all tissues, the addition of azide, an inhibitor of catalase, augmented the rate of oxidation of Me2SO and KTBA. The addition of iron-EDTA (a OH-potentiating agent) increased the rates of oxidation of ethanol by the microsomes from the three tissues. This increase again correlated with an increase in the oxidation of Me2SO and KTBA. The greater rate of oxidation of ethanol and the hydroxyl radical scavengers by liver microsomes may reflect the relative specific content of cytochrome P-450 (6- to 12-fold greater) and specific activity of NADPH-cytochrome c reductase (4-fold greater) in liver as compared to lung and kidney microsomes. Relative turnover numbers (units per nmole cytochrome P-450) demonstrated equivalent activities for liver and kidney, whereas lung had a higher turnover number for ethanol oxidation and hydroxyl radical generation. These data support the hypothesis that the oxidation of ethanol by microsomes may be mediated by the relative capacity of the microsomes to generate hydroxyl radicals during microsomal electron transport, which in turn may be related to the relative content and/or activities of the components of the electron transport chain.
AB - A comparison of the abilities of microsomes from liver, kidney and lung to oxidize ethanol and to generate hydroxyl radicals was conducted to determine if these two variables correlated with one another. The oxidation of 2-keto-4-thiomethylbutyric acid (KTBA) to ethylene, and the production of formaldehyde from dimethylsulfoxide (Mc2SO), served as chemical probes for the detection of the production of hydroxyl radicals by the microsomes. Liver microsomes oxidized ethanol at rates several-fold greater than those found with lung and kidney microsomes. This greater rate of ethanol oxidation by liver microsomes correlated with a greater rate of oxidation of the hydroxyl radical scavengers by the liver microsomes (liver > lung ≈ kidney). In all tissues, the addition of azide, an inhibitor of catalase, augmented the rate of oxidation of Me2SO and KTBA. The addition of iron-EDTA (a OH-potentiating agent) increased the rates of oxidation of ethanol by the microsomes from the three tissues. This increase again correlated with an increase in the oxidation of Me2SO and KTBA. The greater rate of oxidation of ethanol and the hydroxyl radical scavengers by liver microsomes may reflect the relative specific content of cytochrome P-450 (6- to 12-fold greater) and specific activity of NADPH-cytochrome c reductase (4-fold greater) in liver as compared to lung and kidney microsomes. Relative turnover numbers (units per nmole cytochrome P-450) demonstrated equivalent activities for liver and kidney, whereas lung had a higher turnover number for ethanol oxidation and hydroxyl radical generation. These data support the hypothesis that the oxidation of ethanol by microsomes may be mediated by the relative capacity of the microsomes to generate hydroxyl radicals during microsomal electron transport, which in turn may be related to the relative content and/or activities of the components of the electron transport chain.
UR - http://www.scopus.com/inward/record.url?scp=0019952431&partnerID=8YFLogxK
U2 - 10.1016/0006-2952(82)90417-8
DO - 10.1016/0006-2952(82)90417-8
M3 - Article
C2 - 6288048
AN - SCOPUS:0019952431
SN - 0006-2952
VL - 31
SP - 2031
EP - 2037
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 11
ER -