PMID- 10073673
OWN - NLM
STAT- MEDLINE
DCOM- 19990325
LR  - 20141120
IS  - 0033-7587 (Print)
IS  - 0033-7587 (Linking)
VI  - 151
IP  - 3
DP  - 1999 Mar
TI  - Antioxidant effect of probucol on RO2*/O2(*-)-induced peroxidation of human 
      low-density lipoproteins.
PG  - 343-53
AB  - This study was designed to evaluate the antioxidant effect of probucol on 
      peroxidation of low-density lipoproteins (LDLs) initiated by oxygenated free 
      radicals (O2*-) and ethanol-derived peroxyl radicals (RO2*) generated by gamma 
      radiolysis. Initial radiolytic yields related to the markers of lipid 
      peroxidation [i.e. decrease in endogenous alpha-tocopherol, formation of 
      thiobarbituric acid-reactive substances (TBARS) and conjugated dienes] were 
      determined as a function of LDL concentration (1.5 and 3 g l(-1), expressed as 
      total LDL) and in the absence or the presence of probucol at different 
      concentrations (2.3 x 10(-6), 3.5 x 10(-6), 9 x 10(-6) and 20.5 x 10(-6) mol 
      l(-1)). Our results showed that probucol was able to decrease not only the yields 
      of TBARS and conjugated dienes but also the levels of these peroxidation products 
      obtained at high doses (2500 Gy) compared to LDLs without probucol. Under our 
      conditions, probucol displayed an optimal antioxidant effect for an initial 
      concentration in LDLs equivalent to 15 probucol molecules per LDL particle, which 
      corresponded to a pharmacologically relevant concentration of probucol. Moreover, 
      our data showed that probucol was unable to react with RO2* and thus did not 
      protect LDL vitamin E from free radical attack. In addition, the scavenging 
      capacity of probucol on O2*- appeared to be very poor, and probucol more likely 
      reacted with LDL intermediate radical products. Finally, a very significant 
      steady-state level of probucol remained in LDLs at high doses (up to 2500 Gy), 
      equivalent to at least 40% of the initial concentration of probucol. This 
      addressed the question of a mechanism for regeneration of probucol in LDLs. Our 
      results as a whole suggested that the antioxidant effect of probucol in vivo 
      could not be explained by its scavenging capacity with regard to RO2*/O2*- free 
      radicals.
FAU - Bonnefont-Rousselot, D
AU  - Bonnefont-Rousselot D
AD  - Laboratoire de Biochimie, Hopital de la Salpetriere, Paris, France.
FAU - Segaud, C
AU  - Segaud C
FAU - Jore, D
AU  - Jore D
FAU - Delattre, J
AU  - Delattre J
FAU - Gardes-Albert, M
AU  - Gardes-Albert M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Radiat Res
JT  - Radiation research
JID - 0401245
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Solutions)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 059QF0KO0R (Water)
RN  - 11062-77-4 (Superoxides)
RN  - 1406-18-4 (Vitamin E)
RN  - 3K9958V90M (Ethanol)
RN  - P3CTH044XJ (Probucol)
SB  - IM
MH  - Anticholesteremic Agents/pharmacology
MH  - Antioxidants/*pharmacology
MH  - Ethanol/pharmacology
MH  - Free Radical Scavengers/pharmacology
MH  - Free Radicals/metabolism/radiation effects
MH  - Gamma Rays
MH  - Humans
MH  - In Vitro Techniques
MH  - Kinetics
MH  - Lipid Peroxidation/*drug effects/*radiation effects
MH  - Lipoproteins, LDL/*metabolism/*radiation effects
MH  - Probucol/*pharmacology
MH  - Radiochemistry
MH  - Solutions
MH  - Superoxides/metabolism/radiation effects
MH  - Thiobarbituric Acid Reactive Substances/metabolism
MH  - Vitamin E/metabolism/radiation effects
MH  - Water
EDAT- 1999/03/12 00:00
MHDA- 1999/03/12 00:01
CRDT- 1999/03/12 00:00
PHST- 1999/03/12 00:00 [pubmed]
PHST- 1999/03/12 00:01 [medline]
PHST- 1999/03/12 00:00 [entrez]
PST - ppublish
SO  - Radiat Res. 1999 Mar;151(3):343-53.