Aspirin promotes low density lipoprotein susceptibility to oxidative modification in healthy volunteers.
BACKGROUND
Low density lipoprotein oxidation is a major pathogenic pathway in atherosclerosis. Previous studies suggested that aspirin, a commonly prescribed drug in patients with atherosclerosis, when given in a dose of 300 mg/day may decrease LDL susceptibility to oxidative modification. However, the effect of the more common lower dose aspirin on LDL oxidation is not known.


OBJECTIVE
To examine the effect of aspirin administration (low dosage) on the susceptibility of LDL to oxidative modification in healthy volunteers.


METHODS
Aspirin 75 mg was administered daily for 2 weeks to 10 healthy volunteers selected from the medical staff and students at the faculty of medicine. The main outcome measure was ex vivo oxidation of LDL by ultraviolet C irradiation or by peroxyl free radicals generated by AAPH (2,2'-azobis 2-amidinopropane hydrochloride). The extent of LDL oxidation was determined by measuring the formed amounts of thiobarbituric acid-reactive substances, lipid peroxides and conjugated dienes.


RESULTS
Following exposure to UVc irradiation there was a significant (P 0.01) increase (10.8%) in TBARS concentrations and a significant (P < 0.05) increase (5.4%) in PD concentrations in LDL withdrawn after aspirin treatment as compared to LDL withdrawn before aspirin treatment. Following incubation with AAPH there was a significant (P < 0.05) increase (15%) in PD concentrations and a significant (P < 0.05) reduction (10%) of the LDL oxidation lag time in LDL withdrawn after aspirin intake as compared to LDL withdrawn before aspirin treatment.


CONCLUSIONS
Aspirin treatment given to healthy volunteers at a dose of 75 mg/day increased the susceptibility of their plasma LDL to oxidative modification ex vivo. Our study provides, for the first time, in vivo evidence of pro-oxidative properties of aspirin already suggested by previous in vitro trials.
Waterman
Matti
M
Department of Internal Medicine A, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. m_waterman@rambam.health.gov.il
Fuhrman
Bianca
B
Keidar
Shlomo
S
Hayek
Tony
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D010084:Oxidation-Reduction; D014466:Ultraviolet Rays
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008077:Lipoproteins, LDL; D001241:Aspirin