Inhibitors of HMG-CoA reductase are new safe and effective cholesterol-lowering agents. Elevation of alanine-amino transferase (ALT) and aspartate-amino transferase (AST) has been described in a few cases and a myopathy with elevation of creatinine kinase (CK) has been reported rarely. The inhibition of HMG-CoA reductase affects also the biosynthesis of ubiquinone (CoQ10). We studied two groups of five healthy volunteers treated with 20 mg/day of pravastatin (Squibb, Italy) or simvastatin (MSD) for a month. Then we treated 30 hypercholesterolemic patients in a double-blind controlled study with pravastatin, simvastatin (20 mg/day), or placebo for 3 months. At the beginning, and 3 months thereafter we measured plasma total cholesterol, CoQ10, ALT, AST, CK, and other parameters (urea, creatinine, uric acid, total bilirubin, gamma GT, total protein). Significant changes in the healthy volunteer group were detected for total cholesterol and CoQ10 levels, which underwent about a 40% reduction after the treatment. The same extent of reduction, compared with placebo was measured in hypercholesterolemic patients treated with pravastatin or simvastatin. Our data show that the treatment with HMG-CoA reductase inhibitors lowers both total cholesterol and CoQ10 plasma levels in normal volunteers and in hypercholesterolemic patients. CoQ10 is essential for the production of energy and also has antioxidative properties. A diminution of CoQ10 availability may be the cause of membrane alteration with consequent cellular damage.
OBJECTIVE -Diabetes increases the risk of coronary heart disease (CHD) to a greater extent in women than in men. We investigated whether type 1 diabetic patients with short duration of disease and without complications have an altered oxidative status and whether there are differences between men and women.RESEARCH DESIGN AND METHODS -We investigated oxidative status in 29 control subjects and 37 patients with uncomplicated type 1 diabetes with duration of 6 Ϯ 3 years.RESULTS -Compared with control subjects, type 1 diabetic patients had lower total plasma antioxidant capacity (TRAP) (720.3 Ϯ 111.2 vs. 972.5 Ϯ 97.7 mol/l in men, P Ͻ 0.001; 579.8 Ϯ 95.4 vs. 930.1 Ϯ 84.2 in women, P Ͻ 0.001), higher lipid hydroperoxide (ROOH) levels (6.4 Ϯ 2.2 vs. 2.0 Ϯ 0.7 mol/l in men, P Ͻ 0.001; 8.1 Ϯ 1.9 vs. 2.2 Ϯ 0.6 in women, P Ͻ 0.001), higher total conjugated diene (CD) levels (0.037 Ϯ 0.003 vs. 0.033 Ϯ 0.002 A.U. in men, P Ͻ 0.001), lower 246-nm CD levels (0.0032.Ϯ 0.0010 vs. 0.0070 Ϯ 0.0012 A.U. in men, P Ͻ 0.001; 0.0022 Ϯ 0.0011 vs. 0.0072 Ϯ 0.0014 A.U. in women, P Ͻ 0.001), and higher 232-nm CD levels (0.0348 Ϯ 0.0041 vs. 0.0257 Ϯ 0.0022 A.U. in men, P Ͻ 0.001; 0.0346 Ϯ 0.0031 vs. 0.0246 Ϯ 0.0074 A.U. in women, P Ͻ 0.001). Compared with diabetic men, diabetic women had lower TRAP (P Ͻ 0.01), higher ROOH levels (P Ͻ 0.01), and lower 246-nm CD levels (P Ͻ 0.05). Plasma concentration of uric acid was significantly lower in patients with type 1 diabetes than in control subjects (3.3 Ϯ 0.3 vs. 4.3 Ϯ 0.2 mg/dl; P ϭ 0.009) with a significant difference between women and men with type 1 diabetes (2.6 Ϯ 0.3 vs. 3.9 Ϯ 0.3, respectively; P ϭ 0.009).CONCLUSIONS -Our findings suggest that reduced antioxidant activity and increased oxidative stress occur early after the diagnosis of type 1 diabetes, especially in women, and this might explain, at least in part, the increased susceptibility of diabetic women to cardiovascular complications.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations –citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.