Original ContributionAntioxidant and Prooxidant Properties of Captopril and Enalapril
Introduction
The angiotensin-converting enzyme (ACE) inhibitors, captopril (CAP) and enalapril (ENA) (Fig. 1) are widely used in the treatment of hypertension and of congestive heart failure.1, 2 In addition, they retard the progression of chronic renal failure and of diabetic nephropathy.[3] CAP was also reported to have antiinflammatory activity.[4] The beneficial actions of ACE inhibitors have been partly ascribed to antioxidant properties of these compounds, especially of CAP.5, 6, 7, 8 There is a controversy concerning the comparison of antioxidant effects of thiol-group-containing and nonthiol ACE inhibitors. CAP and ENA were found approximally equally active in prevention of LDL oxidation[9] and augmentation of activities of superoxide dismutase and glutathione peroxidase in the liver of experimental animals[10] as well as of erythrocyte Na+,K+-ATPase and Ca2+-ATPase activities in patients with hypertension.[11] On the other hand, only CAP in contrast to non-SH group ACE inhibitors was found to be capable of providing protection against arrhythmias caused by ischemia/reperfusion[12] and protection of cultured endothelial cells against free radical injury.[13] However, there are also reports on the prooxidant action of CAP.14, 15 These controversies prompted us to reexamine the antioxidant properties of CAP in various biochemical systems and to compare CAP with ENA in this respect.
Section snippets
Materials and Methods
All reagents were from Sigma Chemical Co. (Deisenhofen, Germany). Water was purified in a Milli-QPlus system (Millipore) and had a resistivity of 18.2 Megaohm·cm.
Blood was obtained from a local blood bank. Erythrocytes were depleted of leukocyte contamination on cellulose columns and washed with phosphate-buffered saline (145 mM NaCl in 10 mM sodium phosphate buffer, pH 7.4) unless stated otherwise. Erythrocyte membranes were isolated by a modified method of Dodge et al.[16] based on hypotonic
Results
Hemolysis caused by AAPH was slowed down by 100 μM and 200 μM CAP (Fig. 2) but not by ENA (not shown). After 120-min incubation at 37°C, OD of AAPH-treated cell suspensions reached 17% of the initial value while in the presence of 100 μM or 200 μM CAP it was still not different from 100%. After 240 min 100 μM CAP offered no protection but OD of samples containing 200 μM CAP was equal to 81% of the initial value. Hemoglobin oxidation caused by AAPH monitored both by absorbance decrease at 576 nm
Discussion
In none of the experiments performed ENA show any significant antioxidant action. These results are in line with other findings on the significance of the thiol group in the antioxidant action of ACE inhibitors12, 13 and with the recent study showing the ability of CAP but not ENA to scavenge 2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) free radicals.[23] In some systems in which CAP was protective, ENA promoted the oxidant damage (Fig. 5, Fig. 7, and Fig. 8). A plausible
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