Comparison of the free radical-scavenging ability of captopril and ascorbic acid in an in-vitro model of lipid oxidation. Implications for reperfusion injury and ACE inhibitor therapy.
The free radical-scavenging activity of captopril and ascorbic acid was determined by assessing their ability to inhibit the peroxidation of linoleic acid in sodium dodecyl sulphate (SDS) micelles at 37 degrees C. The extent of peroxidation was monitored polarographically using an oxygen electrode to determine oxygen consumption rates. Ascorbic acid was observed to inhibit the peroxidation in a concentration-dependent fashion with an IC50 value of 17 microM. In contrast, the addition of captopril at concentrations up to 500 microM did not result in any detectable inhibition. Unlike ascorbic acid, no synergistic effect, as evidenced by the duration of inhibition, was observed with captopril/alpha-tocopherol mixtures. Measurements of the partitioning of captopril between SDS micelles and the aqueous phase show that 37% of the bulk captopril concentration is localized within the micellar phase; this indicates that phase separation of captopril from the lipid peroxyl radicals is not the cause of the observed lack of inhibitory activity.
Kaufman
M J
MJ
Merck Research Laboratories, West Point, PA 19486.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry*; D004058:Diffusion; D016166:Free Radical Scavengers; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000737:chemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008823:Micelles; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010743:Phospholipids / Q000737:chemistry; D015427:Reperfusion Injury / Q000503:physiopathology*; D012967:Sodium Dodecyl Sulfate
D000806:Angiotensin-Converting Enzyme Inhibitors; D016166:Free Radical Scavengers; D008041:Linoleic Acids; D008823:Micelles; D010743:Phospholipids; D012967:Sodium Dodecyl Sulfate; D002216:Captopril; D019787:Linoleic Acid; D001205:Ascorbic Acid