Angiotensin Converting Enzyme Inhibitors as Oxygen Free Radical Scavengers

Abstract

The authors have compared the ability of two non-SH-containing angiotensin converting enzyme (ACE) inhibitors (enalaprilat and lisinopril) with an -SH containing ACE inhibitor (captopril) to scavenge the hydroxyl radical (.OH). All three compounds were able to scavenge .OH radicals generated in free solution at approximately diffusion-controlled rates (10(10) M-1 s-1) as established by the deoxyribose assay in the presence of EDTA. The compounds also inhibited deoxyribose degradation in reaction mixtures which did not contain EDTA but not so effectively. This later findings also suggests that they have some degree of metal-binding capability. Chemiluminescence assays of oxidation of hypoxanthine by xanthine oxidase in the presence of luminol, confirm that the three ACE inhibitors are oxygen free radical scavengers. Our results indicate that the presence of a sulphydryl group in the chemical structure of ACE inhibitors is not relevant for their oxygen free radical scavenging ability.

Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus.

“…For example, angiotensin II has been found to increase the activity of vascular NADH oxidase in the rat and, probably related to this, the vascular production of superoxide anions, while selective blockade of angiotensin type I receptors reduced superoxide production (39). These studies extend previous observations of antioxidant effects of ACE inhibitor drugs (40)(41)(42)(43) and suggest that suppression of superoxide production is likely to be particularly relevant in the diabetic state (31)(32)(33). Additionally, decreased production of angiotensin II could act through protein kinase C and consequent increase in NO synthase activity, leading to increased NO synthesis (34).…”

Captopril suppresses inflammation in endotoxin-induced uveitis in rats

“…ACE inhibitors including captopril have proven to be beneficial in experimental autoimmune encephalomyelitis (Constantinescu et al, 1995), myocarditis (Godsel et al, 2003), adriamycin-induced myocardial and hematological toxicities (O. Al-Shabanah et al, 1998), Freund`s adjuvant arthritis (Agha and Mansour, 2000) and experimental rats` colitis (Jahovic et al, 2005). The ability of captopril to act as a reactive oxygene species (ROS) scavenger (Mira et al, 1993) was found to be of major importance in its protection against ischemia-reperfusion-induced arrhythmias (Birincioglu et al, 1997) and liver injury in rats (Gulluoglu et al, 1996). An anti-tumor, antifibrotic and cytoprotective effects of captopril have also been demonstrated (Williams et al, 2005;Regan et al, 1996;Murley et al, 2004).…”

The role of the central renin-angiotensin system in Parkinson’s disease

“…According to some authors, only ACE inhibitors with a sulphhydryl group are capable of scavenging ROS, 52,53 whereas others suggest that the free radical scavenging properties are independent of the sulphhydryl group. [54][55][56][57] Although ACE inhibitors such as captopril are potent free radical scavengers in vitro, a scavenger action in vivo is unlikely. In the DATATOP (Deprenyl and Tocopherol Antioxidant Therapy of Parkinson's disease) study, two antioxidants, i.e.…”