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

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and β diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and β diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.
Humans ; Isobutyrates ; Gastrointestinal Microbiome ; Quality of Life ; Stomach Neoplasms/therapy* ; Immunotherapy ; Treatment Outcome

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

This study was aimed to investigate the mechanism of leukemia cell apoptosis induced by histone deacetylase inhibitor (HDACI). Flow cytometry was used to detect the apoptosis of leukemia cell lines NB4, U937 and Jurkat, and the changes of mRNA and protein expressions of TRAIL, DR4 and DR5 were detected by Western blot and RT-PCR respectively. The results showed that both TRAIL and DR5 protein and mRNA expressions in NB4, U937 and Jurkat cells increased after treated with sodium butyrate (SB) and in time-dependent manner. However, DR4 mRNA in leukemia cells was not significantly changed after treated with SB. It is concluded that the apoptosis mechanism of leukemic cell lines NB4, U937 and Jurkat induced by SB is closely related to the protein and mRNA expressions up-regulating TRAIL and DR5, but the DR4 may not participate in the apoptosis induced by SB.
Apoptosis ; drug effects ; Cell Line, Tumor ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Isobutyrates ; pharmacology ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; metabolism

In order to investigate the enzyme production mechanism of yak rumen-derived anaerobic fungus Orpinomyces sp. YF3 under the induction of different carbon sources, anaerobic culture tubes were used for in vitro fermentation. 8 g/L of glucose (Glu), filter paper (Flp) and avicel (Avi) were respectively added to 10 mL of basic culture medium as the sole carbon source. The activity of fiber-degrading enzyme and the concentration of volatile fatty acid in the fermentation liquid were detected, and the enzyme producing mechanism of Orpinomyces sp. YF3 was explored by transcriptomics. It was found that, in glucose-induced fermentation solution, the activities of carboxymethyl cellulase, microcrystalline cellulase, filter paper enzyme, xylanase and the proportion of acetate were significantly increased (P < 0.05), the proportion of propionate, butyrate, isobutyrate were significantly decreased (P < 0.05). The results of transcriptome analysis showed that there were 5 949 differentially expressed genes (DEGs) between the Glu group and the Flp group, 10 970 DEGs between the Glu group and the Avi group, and 6 057 DEGs between the Flp group and the Avi group. It was found that the DEGs associated with fiber degrading enzymes were significantly up-regulated in the Glu group. Gene ontology (GO) function enrichment analysis identified that DEGs were mainly associated with the xylan catabolic process, hemicellulose metabolic process, β-glucan metabolic process, cellulase activity, endo-1,4-β-xylanase activity, cell wall polysaccharide metabolic process, carbohydrate catabolic process, glucan catabolic process and carbohydrate metabolic process. Moreover, the differentially expressed pathways associated with fiber degrading enzymes enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were mainly starch and sucrose metabolic pathways and other glycan degradation pathways. In conclusion, Orpinomyces sp. YF3 with glucose as carbon source substrate significantly increased the activity of cellulose degrading enzyme and the proportion of acetate, decreased the proportion of propionate, butyrate and isobutyrate. Furthermore, the degradation ability and energy utilization efficiency of fungus in the presence of glucose were improved by means of regulating the expression of cellulose degrading enzyme gene and participating in starch and sucrose metabolism pathway, and other glycan degradation pathways, which provides a theoretical basis for the application of Orpinomyces sp. YF3 in practical production and facilitates the application of Orpinomyces sp. YF3 in the future.
Animals ; Cattle ; Neocallimastigales/metabolism* ; Anaerobiosis ; Rumen/microbiology* ; Propionates/metabolism* ; Isobutyrates/metabolism* ; Cellulose/metabolism* ; Fungi ; Starch/metabolism* ; Glucose/metabolism* ; Acetates ; Sucrose/metabolism* ; Cellulases ; Cellulase

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

No abstract available.
Dyslipidemias ; Fibric Acids ; Niacin

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

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