Simvastatin Therapy Reduces Prooxidant‐Antioxidant Balance: Results of a Placebo‐Controlled Cross‐Over Trial

Abstract

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant-antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.

Barberry Administration and Pro-Oxidant–Antioxidant Balance in Patients With Metabolic Syndrome

“…Alamdari et al indicated that PAB may be a potential cardiovascular risk predictor (7). A number of trials have also demonstrated that PAB values may serve as an indicator of oxidative stress (20-23). …”

Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats

“…Statins represent drugs of first choice for treatment of hypercholesterolemia since they inhibit 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in mevalonate and cholesterol biosynthesis [1]. Hypercholesterolemia leads to a pronounced increase in reactive oxygen species (ROS) like free oxygen radicals, oxygen ions, and hydrogen peroxides (H 2 O 2 ) [1].…”

“…Hypercholesterolemia leads to a pronounced increase in reactive oxygen species (ROS) like free oxygen radicals, oxygen ions, and hydrogen peroxides (H 2 O 2 ) [1]. Large amounts of H 2 O 2 stimulate the peroxidation of LDL-cholesterol, which causes a significant amount of malondialdehyde (MDA) formation.…”

“…Experiments in vitro and in vivo have shown that statins contribute to the protection of organism against oxidative stress Pharmacological Reports 67 (2015) 907-913 through their anti-inflammatory and anti-thrombotic actions, and through the scavenging of superoxide anions and hydroxyl radicals [1,[4][5][6]. All these effects are well-known cholesterol-independent or ''pleiotropic'' effects of statins.…”

Simvastatin and Serum Adiponectin Concentrations in Patients With Established Cardiovascular Disease

“…Recent studies have shown that statins has have other properties in addition to lowering the cholesterol level (4), including anti-inflammatory effects (5). We recently reported a significant reduction in mean serum prooxidant-antioxidant balance (PAB) concentrations, a marker of oxidant stress after treatment with simvastatin (6). The pleiotropic effects of statins have been reported previously, but the relative importance of these effects in reducing the CVD risk has been contentious (7).…”