Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients.
The susceptibility of low-density lipoprotein (LDL) to oxidation was studied in hypertriglyceridemic men (5 with type III and 5 with type IV) at baseline on a low-saturated-fat, low-cholesterol diet, after 6 weeks of dietary supplementation with fish oil (Promega, 12 g/d), and after 6 weeks of fish oil combined with probucol (500 mg BID). The relative content of n-3 polyunsaturated fatty acids in plasma and LDL was increased during the two treatment periods, and a low alpha-tocopherol to n-3 polyunsaturated fatty acids ratio was observed. Plasma thiobarbituric acid-reactive substances (TBARS) levels were unchanged after 6 weeks of fish oil, but the ratio of lipid peroxides to the reduced triglyceride (TG) levels (MDA:TG) was significantly higher (P < .01). Addition of probucol lowered both absolute levels of TBARS (P < .01) and the MDA to TG ratio (P < .001). The susceptibility of LDL to Cu(2+)-catalyzed oxidation was evaluated over a 5-hour time course by determining TBARS formation, free amino group levels, and changes in LDL electrophoretic mobility. TBARS levels that were higher in native LDL (1.019 < d < 1.050 g/mL) after 6 weeks of fish oil than at baseline (P < .01) were reduced 52.3 +/- 11.3% by the addition of probucol (P < .001). With fish oil alone, TBARS production after exposure of LDL to Cu2+ for 5 hours was increased 17.0 +/- 5.8% compared with corresponding baseline values (P < .001), whereas a 64.1 +/- 14.3% reduction from the previous period was observed with fish oil + probucol (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Lussier-Cacan
S
S
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Québec, Canada.
Dubreuil-Quidoz
S
S
Roederer
G
G
Leboeuf
N
N
Boulet
L
L
de Langavant
G C
GC
Davignon
J
J
Naruszewicz
M
M
D000328:Adult; D000975:Antioxidants; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003300:Copper / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy; D006953:Hyperlipoproteinemia Type IV / Q000097:blood* / Q000178:diet therapy / Q000188:drug therapy; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011341:Probucol / Q000008:administration & dosage / Q000627:therapeutic use*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood
D000975:Antioxidants; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D005395:Fish Oils; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D014810:Vitamin E; D003300:Copper; D011341:Probucol; C029892:cupric chloride