Ciprofibrate treatment in patients with atherogenic lipoprotein phenotype: effects on HDL quality, LDL susceptibility to oxidation and DNA damage

• Published in: European journal of clinical pharmacology Vol. 54; no. 9-10; pp. 697 - 699
• Main Authors: RASLOVA, K, DOBIASOVA, M, NAGYOVA, A, FABRY, R, RAUCHOVA, H, DUSINSKA, M
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.11.1998; Berlin Springer Nature B.V
• Subjects: Arteriosclerosis - genetics; Biological and medical sciences; Cholesterol; Ciprofibrate; Clofibric Acid - analogs & derivatives; Clofibric Acid - therapeutic use; Comet assay; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA Damage; Female; Fibric Acids; General and cellular metabolism. Vitamins; Genotype & phenotype; Humans; Hypolipidemic Agents - therapeutic use; Kinetics; Lipid metabolism; Lipoproteins; Lipoproteins (high density); Lipoproteins (low density); Lipoproteins - genetics; Lipoproteins, HDL - blood; Lipoproteins, HDL - genetics; Lipoproteins, LDL - blood; Lipoproteins, LDL - genetics; Lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Male; Medical sciences; Middle Aged; Oxidation; Oxidation-Reduction; Pharmacology. Drug treatments; Phenotype; Triglycerides; Human; Fibrate derivatives; Cardiovascular disease; Metabolic diseases; Lipids; Coronary heart disease; Vascular disease; Lipoprotein LDL; Chemotherapy; Ciprofibrate; Treatment; DNA; Atherosclerosis; Oxidation; Dyslipemia; Lipoprotein HDL; Antilipemic agent
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s002280050537

This study was conducted to examine a complex effect of ciprofibrate therapy in patients with atherogenic lipoprotein phenotype. Effects of ciprofibrate were studied on HDL subpopulations, HDL ability to esterify cholesterol (FER(HDL)), susceptibility of LDL to oxidation as well as on in vivo oxidative DNA damage in peripheral lymphocytes, measured as strand breaks (SBs) by the comet assay. Ciprofibrate treatment significantly decreased total cholesterol, and triglycerides, and increased HDL-cholesterol. The FER(HDL) showed a significant reduction (29.5+/-7.4 to 23+/-7.5% x h(-1), P=0.0001). The relative concentrations of HDL subclasses did not differ between baseline and after treatment. Ciprofibrate induced a significant increase in LDL oxidation lag time (93+/-7 to 102=11 min, P=0.02) and a decrease in DNA strand breaks (34.0+/-16.2 to 17.8+/-7.5, P=0.02). A significant correlation between maximal rate of diene production and strand breaks was found (r=0.55, P=0.01). These findings may be explained by an improvement of LDL resistance to oxidation, resulting in a decrease in oxidatively modified LDL's cytotoxic effect. Ciprofibrate treatment favourably affected the quality of plasma HDL, probably by the improvement of triglyceride rich lipoprotein metabolism and/or LDL subpopulation profile, increased LDL resistance to oxidation, and decreased the level of DNA damage in peripheral lymphocytes.