Fenofibrate is one of PPAR-alpha (peroxisome proliferator activated receptor alpha) agonists. Fenofibrate decreases effectively triglyceride and increases high density lipoprotein cholesterol level through the effect on lipoprotein lipase, hepatic production and degradation of lipoproteins. Fenofibrate was recommended as the drug for hypertriglyceridemia treatment in European guideline released in 2011. But American heart association guideline in 2013 did not recommend non-statin therapy including fibrate for the prevention of atherosclerotic cardiovascular disease. But fenofibrate is still considered as the important drug for the management of atherogenic dyslipidemia especially in patients with metabolic syndrome and diabetes to reduce the residual risk after statin therapy from the evidence of many studies. Fibrates including bezafibrate, gemfibrozil, and fenofibrate increased serum creatinine level in several studies. But the mechanism of change in renal function is not clear till now. And the reversibility of renal function with drug discontinuation is dependent on the kinds of fibrate. Fenofibrate increased serum creatinine level, decreased albuminuria and renal function was reversible with the drug discontinuation in large clinical trials. In these days renal function change with fenofibrate therapy in Korean patients with hypertriglyceridemia was investigated. Fenofibrate treatment for 2 months increased serum creatinine level significantly and old age was associated with the change of renal function in multivariate analysis. Short-term therapy significantly increased serum creatinine level even within normal range, and this change may be important in some groups especially old age.
Albuminuria ; American Heart Association ; Bezafibrate ; Cardiovascular Diseases ; Cholesterol, HDL ; Creatinine ; Dyslipidemias ; Fenofibrate* ; Fibric Acids ; Gemfibrozil ; Glomerular Filtration Rate ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypertriglyceridemia ; Lipoprotein Lipase ; Lipoproteins ; Multivariate Analysis ; Reference Values ; Triglycerides

No abstract available.
Dyslipidemias ; Fibric Acids ; Niacin

The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 micrometer) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.
Astrocytes ; Bezafibrate ; Cell Proliferation ; Cytokines ; Fenofibrate ; Fibric Acids ; Interleukin-6 ; PPAR alpha ; RNA, Messenger ; Tumor Necrosis Factor-alpha

OBJECTIVE: To determine the histopathological effect of statins, fibrates and its combination in rat nerves
METHODOLOGY: This is a pilot experimental study. Four male albino rats were used in this study. Each rat was given therapeutic doses of simvastatin alone, gemfibrozil alone, gemfibrozil and simvastatin combination and placebo. On day 21, the sciatic nerve was harvested for histopathologic examination
RESULTS: Although not marked, the combination of simvastatin and gemfibrozil produced more axonal degeneration than did simvastatin alone or gemfibrozil alone. Axonal degeneration was documented on teased nerve fibers and epon cross sections
CONCLUSION: The use of lipid lowering agents may induce peripheral neuropathy Recommendation: This pilot study serves as rationale to proceed with an experiment not only to document neuropathy but also correlate the possible association of the pathomechanism of myotoxicity and neurotoxicity of lipid lowering agents.

Animal ; Rats ; Simvastatin ; Gemfibrozil ; Hydroxymethylglutaryl-coa Reductase Inhibitors ; Fibric Acids ; Hypolipidemic Agents ; Sciatic Nerve ; Peripheral Nervous System Diseases ; Epon ; Epoxy Resins ; Nerve Fibers

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.
Cardiovascular Diseases ; Diabetes Complications ; Fibric Acids ; Homeostasis ; Inflammation ; PPAR alpha*

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-alpha (PPAR-alpha) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-alpha, summarize data from clinical studies on the effect of PPAR-alpha agonist in diabetes, and will discuss the possible therapeutic role of PPAR-alpha activation.
Cardiovascular Diseases ; Diabetes Complications ; Fibric Acids ; Homeostasis ; Inflammation ; PPAR alpha*

BACKGROUND: High levels of C-reactive protein (CRP) are associated with an increased risk for cardiovascular diseases. Most reports on the effect of fibrate on CRP level have inadequate study designs and the results are inconsistent. This study was designed to evaluate the effect of fenofibrate on CRP levels in hypertriglyceridemic patients. METHODS: Patients with triglyceride (TG) level over 200 mg/dL were treated with 200 mg of fenofibrate (Fenofibrate group, n=30) or with general measures (Control group, n=30). Patients with CRP levels >10 mg/L were excluded. Patients with hypercholesterolemia were treated with HMG CoA reductase inhibitor (Statin group, n=30). Lipid and lipoprotein levels were measured before and 2 months after medication. RESULTS: Baseline characteristics were similar in Fenofibrate and Control groups. Baseline CRP levels were independently associated with the presence of diabetes mellitus. Fenofibrate therapy did not change CRP levels (1.67+/-1.60 vs 1.76+/-1.88 mg/L, p=0.79) as did Control group (p=0.46). When both Fenofibrate and Control groups were divided into three subgroups in terms of baseline CRP levels, CRP levels were increased in the lowest group (p=0.019), did not change in the middle and the highest groups (p=0.89 and p=0.47 respectively). In patients with baseline CRP level > or =3 mg/L, CRP levels were decreased (p=0.041). Changes of CRP levels were independently associated with baseline CRP levels. Statin therapy decreased CRP levels (p=0.046). CONCLUSIONS: Fenofibrate did not change CRP levels in hypertriglyceridemic patients. Cardioprotective effects of fibrates may not be associated with anti-inflammatory mechanisms in contrast to those of statins.
C-Reactive Protein* ; Cardiovascular Diseases ; Diabetes Mellitus ; Fenofibrate* ; Fibric Acids ; Humans ; Hydroxymethylglutaryl CoA Reductases ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Hypercholesterolemia ; Lipoproteins ; Triglycerides

BACKGROUND: Fibrates are widely used to treat hypertriglyceridemia, a risk factor for arteriosclerosis, but these compounds have been associated with renal dysfunction. This study aimed to investigate the effects of fibrates on renal function in relatively healthy adult subjects with no cardiovascular diseases. METHODS: This retrospective study included 558 outpatients who were prescribed 160 mg fenofibrate (fenofibrate group) or 10 mg atorvastatin (control group) between August 2007 and October 2015. The groups were randomly matched using propensity scores at a 1:1 ratio. Serum creatinine levels and estimated glomerular filtration rates before and after treatment were compared between the two groups. RESULTS: Patients in the fenofibrate group showed greater changes in serum creatinine levels than those in the control group (9.73%±9.83% versus −0.89%±7.37%, P<0.001). Furthermore, 55.1% of patients in the fenofibrate group, but only 6.1% of those in the control group, exhibited a serum creatinine level increase ≥0.1 mg/dL (P<0.001). The fenofibrate group showed significantly greater declines in the estimated glomerular filtration rate than the control group (−10.1%±9.48% versus 1.42%±9.42%, P<0.001). Moreover, 34.7% of the fenofibrate group, but only 4.1% of the control group, exhibited an estimated glomerular filtration rate decrease ≥10 mL/min·1.73 m² (P<0.001). CONCLUSION: Fenofibrate treatment resulted in increased serum creatinine levels and reduced estimated glomerular filtration rates in a primary care setting. Therefore, regular renal function monitoring should be considered essential during fibrate administration.
Adult ; Arteriosclerosis ; Atorvastatin Calcium ; Cardiovascular Diseases ; Creatinine ; Fenofibrate* ; Fibric Acids ; Glomerular Filtration Rate ; Humans ; Hypertriglyceridemia ; Outpatients ; Primary Health Care ; Propensity Score ; Retrospective Studies ; Risk Factors

Latest guidelines on lipid management recommend statins as the first-line therapy. Because limited evidence is available on cardiovascular outcomes with varying statin-nonstatin combinations, recommendation levels for these regimens have been weak. However, a recent trial has demonstrated the additive effect of the statin-ezetimibe combination. The statin-fibrate combination has shown an effect in certain subgroups and on diabetic microangiopathy. Recent trials using the statin-niacin combination have been largely negative, whereas the statin-omega-3 fatty acids combination demonstrated a positive effect only in one study. Identifying the benefits and limitations of each combination is important for the best possible management of patients.
Diabetic Angiopathies ; Drug Therapy* ; Ezetimibe ; Fatty Acids ; Fibric Acids ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Niacin

PURPOSE: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) alpha and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). MATERIALS AND METHODS: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. RESULTS: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 microM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARalpha and PPARgamma were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARalpha were not increased with FF. However, the mRNA of PPARgamma was increased with FF. CONCLUSION: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARalpha.
Catalase ; Cell Line ; Fenofibrate ; Fibric Acids ; Hand ; HeLa Cells ; Humans ; Hypolipidemic Agents ; Ligands ; Peroxisomes ; Polymerase Chain Reaction ; PPAR alpha ; PPAR gamma ; Radiation Tolerance ; Reactive Oxygen Species ; RNA, Messenger ; Superoxide Dismutase ; Superoxides ; Uterine Cervical Neoplasms