Search

Abstract: The effect of ciprofibrate therapy on plasma lipids and lipoproteins, HDL and LDL subfraction profile, fractional esterification rate of HDL cholesterol (FERHDL) and the resistance of LDL and serum lipids to oxidation was studied in 24 males with type 2 diabetes and atherogenic lipoprotein phenotype (ALP). We also examined the effect of ciprofibrate therapy on oxidative DNA damage in peripheral lymphocytes. No differences in glucose, HbA1C and BMI levels were found after three months of ciprofibrate therapy. Ciprofibrate significantly decreased total cholesterol and triglyceride levels by 5.5% and 50% (p = 0.05; 0.001, respectively) and increased HDL-cholesterol levels by 8.5% (p = 0.05). FERHDL and LDL subfraction profile were also favorably affected, However, no effect on HDL subclasses was found. There were no statistically significant differences in lipid resistance to oxidation measured in serum and in LDL (lag time and Vmax) before and after therapy. No significant effect of ciprofibrate was found on oxidative DNA damage. The evaluation of the relationship between oxidative damage purines with lag time in LDL and maximal rate of serum lipid oxidation showed significant correlations after therapy (r = −0.58; 0.47, p = 0.01; 0.05, respectively), but only trends before starting ciprofibrate treatment. Type 2 diabetes mellitus represents a complex metabolic disorder expressed in glucose and lipoprotein disturbances and increased oxidative stress. Ciprofibrate therapy favorably affected major features of lipid abnormalities of diabetic patients, but the level of oxidative stress assessed by in vitro and in vivo methods was not changed. The evaluation of expected logical correlations between the parameters of lipoprotein metabolism, lipid resistance in serum and LDL, and oxidative DNA damage showed that those correlations were more relevant and significant after ciprofibrate treatment and were not related with glucose homeostasis.

Abstract: Objective: We examined the relationship between plasma levels of fenofibric acid, the active metabolite of fenofibrate, and differences in concentrations of plasma lipids, in subjects with primary type IIA or IIB hyperlipoproteinemia (HLP). Subjects and methods: Twenty-nine patients (13 with type IIA and 16 with type IIB HLP) were treated with a single daily 200-mg dose of micronized fenofibrate for 3␣months, after which the plasma levels of fenofibric acid were determined by HPLC after an overnight fast. Results: In the type IIA HLP phenotype, statistically significant correlations were found between fenofibric acid levels and changes in total cholesterol, LDL-C and apo-B at all three control visits, with the highest correlation coefficients at V3 visit (total cholesterol , LDL-C , apo-B ). In type IIB HLP, statistical significance was confirmed only when performing an analysis of pooled values for total cholesterol and LDL-C (, , respectively). The high correlation between plasma fenofibric acid levels and its effect on betalipoprotein changes might reflect the effect of fenofibrate on the catabolism of plasma LDL by the LDL receptor, since that type of relationship is typical of drugs which directly influence the target compartment without an effect on intermediary steps of metabolism. An explanation for the different levels of correlations in type IIA and IIB patients might be found in their different metabolic defects. The fact that fenofibrate's impact on VLDLs is such an important part of its effect on lipoprotein metabolism supports the concept that the effect of circulating fenofibric acid is less pronounced on the LDL receptor in type IIB HLP.

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 (FERHDL), 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 FERHDL 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.