TY - JOUR
T1 - Microsomal metabolism of hydroxyl radical scavenging agents
T2 - Relationship to the microsomal oxidation of alcohols
AU - Cohen, Gerald
AU - Cederbaum, Arthur I.
N1 - Funding Information:
1 Supported by the following grants from the United States Public Health Service: NS-05184 (Clinical Center for the Study of Parkinson’s and Allied Diseases), AA-03508 (Alcohol Research Center), 5K02-AA-0003 (Career Development Award to A. I. C.), and AA-03312. 2 Abbreviations used: Me,SO, dimethylsulfoxide; KTBA, Z-keto-4-thiomethylbutyric acid; ‘OH, hydroxyl radical.
PY - 1980/2
Y1 - 1980/2
N2 - Previous studies provided indirect evidence that hydroxyl radicals are involved in the oxidation of primary aliphatic alcohols by rat liver microsomes. In the current study, three ·OH scavengers were used as chemical probes to evaluate ·OH production by microsomes. The scavengers and their products were 3-thiomethylpropanal (methional) and 2-keto-4-thiomethylbutyric acid, which yield ethylene gas, and dimethylsulfoxide, which yields methane gas. We observed that microsomes actively generate the appropriate hydrocarbon gas from each scavenger when electron transport is initiated with NADPH. Hydrocarbon gas production is augmented by 0.5 mm azide, an agent which inhibits catalase and, thereby, permits H2O2 to accumulate. However, no metabolism of scavengers occurs when H2O2 is added in the absence of microsomes. These results are consistent with a presumed role for H2O2 as a precursor of hydroxyl radicals. In addition, no metabolism of scavengers occurs when azide and H2O2 are added either to boiled microsomes or to intact microsomes in the absence of electron transport (NADPH-generating system omitted). Therefore, both H2O2 and simultaneous electron transport are required. Ethanol inhibits the metabolism of the scavengers. Similarly, the scavengers inhibit the oxidation of ethanol to acetaldehyde; inhibition in the presence of azide is competitive. These latter results indicate a competition between the scavengers and ethanol for metabolically generated ·OH in microsomes. The specificity of this interaction is evident from the observation that the scavengers do not affect the activities of microsomal aminopyrine demethylase or aniline hydroxylase. Two model ·OH-generating systems (Fenton's reagent and iron-EDTA-ascorbate) were also studied and they produced acetaldehyde from ethanol and hydrocarbon gases from the scavengers. These results, as a whole, tend to verify a role for ·OH in the microsomal oxidation of alcohols.
AB - Previous studies provided indirect evidence that hydroxyl radicals are involved in the oxidation of primary aliphatic alcohols by rat liver microsomes. In the current study, three ·OH scavengers were used as chemical probes to evaluate ·OH production by microsomes. The scavengers and their products were 3-thiomethylpropanal (methional) and 2-keto-4-thiomethylbutyric acid, which yield ethylene gas, and dimethylsulfoxide, which yields methane gas. We observed that microsomes actively generate the appropriate hydrocarbon gas from each scavenger when electron transport is initiated with NADPH. Hydrocarbon gas production is augmented by 0.5 mm azide, an agent which inhibits catalase and, thereby, permits H2O2 to accumulate. However, no metabolism of scavengers occurs when H2O2 is added in the absence of microsomes. These results are consistent with a presumed role for H2O2 as a precursor of hydroxyl radicals. In addition, no metabolism of scavengers occurs when azide and H2O2 are added either to boiled microsomes or to intact microsomes in the absence of electron transport (NADPH-generating system omitted). Therefore, both H2O2 and simultaneous electron transport are required. Ethanol inhibits the metabolism of the scavengers. Similarly, the scavengers inhibit the oxidation of ethanol to acetaldehyde; inhibition in the presence of azide is competitive. These latter results indicate a competition between the scavengers and ethanol for metabolically generated ·OH in microsomes. The specificity of this interaction is evident from the observation that the scavengers do not affect the activities of microsomal aminopyrine demethylase or aniline hydroxylase. Two model ·OH-generating systems (Fenton's reagent and iron-EDTA-ascorbate) were also studied and they produced acetaldehyde from ethanol and hydrocarbon gases from the scavengers. These results, as a whole, tend to verify a role for ·OH in the microsomal oxidation of alcohols.
UR - http://www.scopus.com/inward/record.url?scp=0018841669&partnerID=8YFLogxK
U2 - 10.1016/0003-9861(80)90300-8
DO - 10.1016/0003-9861(80)90300-8
M3 - Article
C2 - 7362238
AN - SCOPUS:0018841669
SN - 0003-9861
VL - 199
SP - 438
EP - 447
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -