PMID- 8077847
OWN - NLM
STAT- MEDLINE
DCOM- 19941003
LR  - 20210217
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 35
IP  - 6
DP  - 1994 Jun
TI  - A critical assessment of the effects of aminoguanidine and ascorbate on the 
      oxidative modification of LDL: evidence for interference with some assays of 
      lipoprotein oxidation by aminoguanidine.
PG  - 1085-92
AB  - Several lines of evidence support a role for oxidized low density lipoprotein 
      (LDL) in the genesis of the atherosclerotic lesion. Hence, the effect of 
      compounds with antioxidant properties on LDL oxidation assumes great 
      significance. Ascorbate, a potent water-soluble chain-breaking antioxidant, has 
      been shown to inhibit LDL oxidation. Aminoguanidine (AMG) is a pharmacological 
      inhibitor of advanced non-enzymatic glycosylation. Recently it has been suggested 
      that aminoguanidine might have an inhibitory effect on LDL oxidation, but total 
      lipid peroxidation assayed by conjugated diene formation was not inhibited. Thus, 
      in this study, we compared the effect of aminoguanidine with ascorbate to obtain 
      a better appreciation of the effect of AMG on Cu(2+)-catalyzed LDL oxidation. 
      Oxidative modification of LDL was monitored by assaying intermediates and end 
      products of lipid peroxidation, conjugated dienes (CD), lipid peroxides (LPO), 
      and relative electrophoretic mobility (REM). Apolipoprotein B-100 modification 
      (increased fluorescence, fragmentation on SDS-PAGE, and 125I-labeled LDL 
      degradation by human macrophages) was also measured. Ascorbate (100 microM) 
      inhibited LDL oxidation by > 95%, as evidenced by all of the selected indices. 
      Aminoguanidine (20 mM) substantially decreased thiobarbituric acid-reactive 
      substances (TBARS) activity and lipid peroxide formation, but only partially 
      prevented the increase of REM (-55%), apoB fluorescence (-39%), and degradation 
      by macrophages (-54%). Unlike ascorbate, AMG failed to preserve alpha-tocopherol 
      in LDL, prevent apoB-100 fragmentation, or inhibit conjugated diene formation 
      during LDL oxidation. Furthermore, incubation of AMG with already oxidized LDL 
      resulted in a significant decrease in TBARS activity and LPO, and 26.9% decrease 
      in the REM of LDL.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Scaccini, C
AU  - Scaccini C
AD  - Center for Human Nutrition, University of Texas, Southwestern Medical Center at 
      Dallas 75235.
FAU - Chiesa, G
AU  - Chiesa G
FAU - Jialal, I
AU  - Jialal I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Apolipoprotein B-100)
RN  - 0 (Apolipoproteins B)
RN  - 0 (Guanidines)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 789U1901C5 (Copper)
RN  - PQ6CK8PD0R (Ascorbic Acid)
RN  - SCQ4EZQ113 (pimagedine)
SB  - IM
MH  - Apolipoprotein B-100
MH  - Apolipoproteins B/metabolism
MH  - Ascorbic Acid/*pharmacology
MH  - Copper/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Guanidines/administration & dosage/*pharmacology
MH  - Humans
MH  - Kinetics
MH  - Lipid Peroxidation/*drug effects
MH  - Lipoproteins, LDL/*metabolism
MH  - Macrophages/metabolism
MH  - Oxidation-Reduction
MH  - Thiobarbituric Acid Reactive Substances/metabolism
EDAT- 1994/06/01 00:00
MHDA- 1994/06/01 00:01
CRDT- 1994/06/01 00:00
PHST- 1994/06/01 00:00 [pubmed]
PHST- 1994/06/01 00:01 [medline]
PHST- 1994/06/01 00:00 [entrez]
AID - S0022-2275(20)40104-X [pii]
PST - ppublish
SO  - J Lipid Res. 1994 Jun;35(6):1085-92.