Atorvastatin and fenofibrate combination induces the predominance of the large HDL subclasses and increased apo AI fractional catabolic rates in New Zealand white rabbits with exogenous hypercholesterolemia

Abstract

The anti-atherogenic properties of high-density lipoproteins (HDLs) may be related to their structure and metabolism. The HDL physicochemical characteristics that determine their plasma clearance during treatment with statins and fibrates are not well understood. In this study, we analyzed HDL-apo AI fractional catabolic rates (FCRs), size distributions, and the lipid composition of the HDL subclasses in New Zealand white rabbits with exogenous dyslipidemia that received low doses of atorvastatin and fenofibrate. Hypercholesterolemia decreased only partially with the combination of both drugs. HDL size distribution shifted toward larger particles among the groups of rabbits that received atorvastatin, fenofibrate, or their combination, compared with both the control group and the dyslipidemic group. The HDL subclasses were significantly rich in cholesterol in each of the groups compared with controls. The structural changes noted in the HDL subclasses were not associated with impaired plasma paraoxonase-1 (PON1) activity. The groups receiving monotherapy and the drug combination group were all associated with a higher apo AI FCR value compared with both the dyslipidemic rabbits and the control group. In conclusion, the combination of atorvastatin and fenofibrate induced a more favorable HDL subclass profile than did the individual use of these drugs. Similarly, the apo AI FCR values were augmented in every group receiving drug treatment (either monotherapy or combination therapy) in the setting of hypercholesterolemia. The anti-atherogenic properties of HDLs, excluding their capacity to bind PON1, may be enhanced by the structural and metabolic modifications induced by the combination of atorvastatin and fenofibrate.

Fenofibrate Therapy Restores Antioxidant Protection and Improves Myocardial Insulin Resistance in a Rat Model of Metabolic Syndrome and Myocardial Ischemia: The Role of Angiotensin II

“…Administration of fenofibrate significantly reduced triglycerides and non-HDL-C levels in MetS animals. These results agree with previous studies that demonstrated the anti-dyslipidemic effect of fenofibrate by changing low density lipoprotein (LDL) particle morphology and reducing triglycerides in humans and animal models [ 21 , 22 , 23 ].…”

Ameliorative effect of statin therapy on oxidative damage in heart tissue of hypercholesterolemic rabbits

“…SOD activity has been reported to be unaffected and higher in previous studies with atherogenesis [38][39][40][41][42][43]. Decreased SOD activity in erythrocytes, after 8 weeks of atorvastatin treatment, indicates the antioxidant effect of the drug [27,[45][46][47][48]. Codoñer-Franch et al [44] found that SOD activity was reduced in hypercholesterolemic children compared to the control group.…”

“…Increased SOD activity represents an important physiological adaptation counteracting the increase in oxidative stress. Decreased SOD activity in erythrocytes, after 8 weeks of atorvastatin treatment, indicates the antioxidant effect of the drug [27,[45][46][47][48]. Statins have been widely used in clinical practice owing to its both potent lipid-modifying effects and other cardio-protective effects including increasing/decreasing SOD generation.…”

<p>Fenofibrate potentiates chemosensitivity to human breast cancer cells by modulating apoptosis via AKT/NF-&kappa;B pathway</p>

“…As an important therapy of hyperlipidemia and hypercholesterolemia, fenofibrate is recently studied in anti-tumor effects in multiple cancer types 10,13,21–23. Its anti-tumor functions such as suppression of cancer cell growth,12 restraining cancer cell metastasis24 and inhibiting carcinogenesis,25 inducing cell-cycle arrest and apoptosis by suppression of Bcl-2, and AKT phosphorylation in prostate cancer26 were discovered during recent years.…”