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

Abstract

Objectives: This study was conducted to examine a complex effect of ciprofibrate therapy in patients with atherogenic lipoprotein phenotype.

Methods: 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.

Results: 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% · 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.

Conclusion: 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.