Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 88
Filter
1.
J. appl. oral sci ; 30: e20210648, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1365014

ABSTRACT

Abstract Inflammation-related immune responses and bone metabolism lead to extensive tooth loss in periodontitis. Objective: This study aims to investigate the effect of peroxisome proliferator-activated receptor (PPAR) alpha agonist anti-inflammatory treatment in vitro and in ligature-induced experimental periodontitis in vivo . Methodology: Splenocytes were isolated from C57BL/6J mice and cultured for 48 hours under the following conditions: control, P. gingivalis lipopolysaccharide (LPS) (1 µg/ml); experimental, LPS (1 µg/ml) + PPARα agonist (fenofibrate) at 1, 10, 50, 100 µM. MRNA and secreted protein levels of TNF-α expression were detected by RT-qPCR and ELISA, respectively. Silk ligatures (7-0) were tied around maxillary second molars of C57BL/6J mice for two weeks. Optimized doses of fenofibrate (50 µM) and vehicle control were injected into the contralateral side of the palatal gingiva on days three, six, and nine. At day 14, bone resorption, osteoclastogenesis, and gingival mRNA expression levels of TNF-α, IL-1β, IL-6, and RANKL/OPG were measured by micro-computed tomography, Tartrate-resistant acid phosphatase (TRAP) staining, and Real-time quantitative PCR, respectively. Results: TNF-α expression in cultured spleen cells were significantly increased in the presence of LPS, when compared with the control group, and significantly reduced by fenofibrate treatment in a dose-dependent manner from 1-100 µM (p<0.05). Gingival mRNA levels of TNF-α, IL-1β, IL-6, and the ratio of RANKL/OPG, were significantly decreased after injection of fenofibrate, when compared to the control side (p<0.05). Periodontal bone loss and TRAP positive cell formation were significantly decreased on the side with an injection of fenofibrate, as compared to the control side (p<0.05). Conclusions: An anti-inflammatory treatment, PPARα agonist, inhibited inflammation and periodontal bone loss in ligature-induced experimental periodontitis.

2.
Article in English | WPRIM | ID: wpr-881081

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.

3.
Chinese Pharmaceutical Journal ; (24): 1372-1375, 2020.
Article in Chinese | WPRIM | ID: wpr-857614

ABSTRACT

OBJECTIVE: To explore clinical characteristics of rhabdomyolysis caused by fenofibrate in patients with hypothyroidism. METHODS: A clinical case was analyzed and summarized the literature of adverse reactions of rhabdomyolysis caused by fenofibrate in patients with hypothyroidism reported in China and abroad. RESULTS: A 25-year-old female with hyperlipidemia combined with hypothyroidism developed rhabdomyolysis at 12th day after taking fenofibrate. Before the occurrence of rhabdomyolysis, highlevelof TSH was detected. After occurrence of adverse reactions, the patient stopped taking fenofibrate, rehydrated and alkalized urine. Then the patient recovered and discharged. In the literature review, 11 cases of rhabdomyolysis with fenofibrate in hypothyroidism were included. The age range was 25-68. The sex ratio was 1∶2. On thyroid function, there were 3 cases unknown, 6 cases with hypothyroidism and 2 cases with FT4 at the lowest normal limit. On doses of fenofibrate, there were 9 cases under the instructions, and 3 cases beyond the recommendations in labeling. Most adverse drug reactions (ADRs) occurred at the third to 60th day after taking fenofibrate. Ten patients recovered and 2 patients improved. CONCLUSION: Hypothyroidism would be a risk factor for rhabdomyolysis caused by fenofibrate. Thyroid function should be monitored in patients taking fenofibrate with hypothyroidism.

4.
Journal of Clinical Hepatology ; (12): 829-834, 2020.
Article in Chinese | WPRIM | ID: wpr-819189

ABSTRACT

ObjectiveTo investigate the effect of fenofibrate on the diversity of intestinal flora in mice with nonalcoholic fatty liver disease (NAFLD). MethodsA total of 30 mice were randomly divided into normal group, high-fat group, and fenofibrate treatment group, with 10 mice in each group. The mice in the high-fat group and the fenofibrate treatment group were given high-fat diet intervention for 14 weeks, and those in the normal group were given normal diet for 14 weeks. After 10 weeks of dietary intervention, the mice in the fenofibrate treatment group were given fenofibrate by gavage and high-fat diet for another 4 weeks, and the change in body weight was monitored during the whole process. Fecal samples were collected after 14 weeks, and high-throughput sequencing 16S rRNA was used to investigate the diversity and difference of intestinal flora. Liver tissue samples were collected, and HE staining and oil red O staining were performed to observe the degree of steatosis. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsAfter 10 weeks of intervention, the fenofibrate treatment group had a significantly lower body weight than the high-fat group (P<0.05). The results of HE staining and oil red O staining showed that the fenofibrate treatment group had a significantly lower degree of fat deposition than the high-fat group. There was a significant difference in intestinal flora between the fenofibrate treatment group and the high-fat group, while there was no significant difference in intestinal flora between the fenofibrate treatment group and the normal group. The fenofibrate treatment group had significant increases in the abundance of Bacteroidetes, Verrucomicrobia, Faecalibaculum, Muribaculaceae_norank, and Akkermansia and significant reductions in the abundance of Firmicutes, Actinobacteria, Clostridium, Turicibacter, and Bifidobacterium. ConclusionThe increases in the abundance of Bacteroidetes and Verrucomicrobia and the reductions in the abundance of Firmicutes and Actinobacteria suggest that fenofibrate may have positive significance in the treatment of NAFLD.

5.
Article | IMSEAR | ID: sea-189135

ABSTRACT

Background: Abnormalities in plasma lipoproteins and deranged lipid metabolism rank as most firmly established and best understood risk factor for atherosclerosis Lipid regulating drugs, may be prescribed if, dietary therapy and lifestyle modification fails to adequately normalize blood lipid levels. The European / Atherosclerosis Society and National Cholesterol Education Programme (NCEP) consider fibric acid derivatives (Fibrates) and Hydroxy Methylglutaryl CoA reductase inhibitors (HMG CoA reductase inhibitors) to be effective therapy for combined dyslipidernia . The aim of present study was to compare the efficacy of Atorvastatin and Fenofibrate on various aspects of lipid profile viz. total cholesterol, serum LDL-C, serum VLDL, serum HDL-C and serum triglycerides in Indian patients having dyslipidemia. Methods: This study was conducted on 100 patients with abnormal lipid profile attending the OPD/Wards of Department of Medicine, Guru Nanak Dev Hospital, attached to Government Medical College, Amritsar. Results: The patients were randomly divided into 2 groups of 50 each, group A and B. Group A were put on Atorvastatin 10-20 mg daily and Group B were put on micronized Fenofibrate 200mg daily. Conclusion: The study concluded that none of these drugs were independently able to achieve NCEP ATP III goals. Atorvastatin has main effect or total serum cholesterol and LDL-C whereas Fenofibrate has main effect on serum triglycerides, VLDL-C and HDL-C .Combination of these may be tried to achieve the desired goal.

6.
J. bras. nefrol ; 41(3): 393-399, July-Sept. 2019. graf
Article in English | LILACS | ID: biblio-1040251

ABSTRACT

Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.


Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.


Subject(s)
Humans , Male , Female , Child, Preschool , Adult , Middle Aged , Kidney Diseases/pathology , Kidney Diseases/therapy , Apolipoproteins E/genetics , Sex Factors , Kidney Transplantation , Treatment Outcome , Kidney Diseases/complications , Kidney Diseases/genetics , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/etiology , Mutation , Hypolipidemic Agents/therapeutic use
7.
Article | IMSEAR | ID: sea-200699

ABSTRACT

Fibrates are a class ofmedication that mainly lowers theblood triglyceride levels. Theyreduce the LDL andincrease the levels of HDL C, in the blood.Clofibrate,the first member to bediscovered in 1962, and introduced in USA in 1967, is withdrawnin 2002, due to unexplained hepatomegaly,hepato-toxicity and possible risk of hepatic cancer. Other fibrates are introduced in the late 1970s and early1980s, such as gemfibrozil in the United States and bezafibrate and ciprofibrate in Europe. Their lipid lowering effects are found to decrease CVS risk , progression of atherosclerosis and metabolic syndrome, macrovascular and microvascular diabetic complications like stroke, myocardial infarction, peripheral vascular diseaseand diabeticretinopathy .Various clinical trials like VA-HIT trial (Veterans Affairs High-Density LipoproteinCholesterol Intervention Trial) , FIELD trail. (the Fenofibrate Intervention and Event Lowering in Diabetes) Helsinki Heart Study,ACCORD -Lipid trial (The lipid component of the Action to Control Cardiovascular Risk in Diabetes trial ) and BIP (Bezafibrate Infarction Prevention Study) trial andangiography trials, like LOCAT(LopidCoronary Angiography Trial) and BECLAIT(Bezafibrate Coronary Atherosclerosis Intervention Trial)demonstrated thebeneficial effects of gemfibrozil and fenofibrate.Their mechanism of action remained obscure for three decades,ie till 1990s, when theirmode of actionwas found. The Mechanism of action of fibrates include limitation of substrate availability for triglyceride synthesis in the liver, promotion of the action of lipoprotein lipase, (LPL)modulation of low density lipoprotein receptor/ligand interaction and stimulation of reverse cholesterol transport The biochemical and molecular mechanisms involvingthevariousenzymes like LCAT (Lecithin-cholesterol acyl transferase)andCYP7A1 etc. (cholesterol 7-alpha-monooxygenase or cytochromeP450 7A1 (CYP7A1)) , transporters like ABC , CETP (ATP-binding cassette transporter, Cholesterol ester binding protein) and NTCP,OATP (Na+-dependent taurocholate transporter/ organic anion transporters) . These are the.) andnuclear factors like LXR, PPAR alfa etc. (liver orphan receptorα , and peroxisome proliferative nuclear factor) , in relation to the mechanismsof action of fibrates are discussed . Areas of current interests in literature are briefed.

8.
Article | IMSEAR | ID: sea-200197

ABSTRACT

Background: Trials of atorvastatin combined either with fenofibrate or with omega-3 fatty acids (O3FA) have shown promising results in atherogenic dyslipidemia but there are very few studies where both these TGs lowering agents have been compared with each other. This study was conducted to compare efficacy and safety of these two agents on lipid profile of patients of atherogenic dyslipidaemia on background statin therapy and also to monitor effects of these interventions on serum uric acid (SUA) levels.Methods: About 90 patients of dyslipidemia were randomised to 3 groups and received O3FA (2000 mg), fenofibrate (80 mg) or dietary restrictions, each with atorvastatin (20 mg) in background for a period of 90 days. Total cholesterol (TC), HDL-C,TGs, LDL-C, SGOT and SGPT levels were done at baseline, 6 weeks and 12 weeks. Other parameters (SUA and BMI) were done at baseline and 12 weeks.Results: Both group 1 (O3FA) and group 2 (fenofibrate) showed highly significant fall in TG levels (p <0.001) in comparison to group 3 (dietary restrictions) whereas comparative TG reduction between groups 1 and group 2 was not significant. Group 2 also showed significant fall in LDL-C levels (p <0.01) in comparison to group 3. LDL-C reduction, TG reduction and SUA reduction was more in group 2 compared to group 1 followed by group 3. No significant difference was observed in the incidence of adverse effects in three study groups.Conclusions: Combination of fenofibrate and atorvastatin was more effective than that of omega-3 fatty acid and atorvastatin, in lowering serum TG and LDL-C levels. There was a significant reduction in SUA levels in all three groups, but combination of fenofibrate and atorvastatin again showed better outcomes. With respect to the safety, all the 3 groups were comparable. O3FA, however, may be a good alternative to fibrates in patients not tolerating latter.

9.
Neuroscience Bulletin ; (6): 15-24, 2019.
Article in English | WPRIM | ID: wpr-775480

ABSTRACT

Fenofibrate, an agonist for peroxisome proliferator-activated receptor alpha (PPAR-α), lowers blood pressure, but whether this action is mediated via baroreflex afferents has not been elucidated. In this study, the distribution of PPAR-α and PPAR-γ was assessed in the nodose ganglion (NG) and the nucleus of the solitary tract (NTS). Hypertension induced by drinking high fructose (HFD) was reduced, along with complete restoration of impaired baroreceptor sensitivity, by chronic treatment with fenofibrate. The molecular data also showed that both PPAR-α and PPAR-γ were dramatically up-regulated in the NG and NTS of the HFD group. Expression of the downstream signaling molecule of PPAR-α, the mitochondrial uncoupling protein 2 (UCP2), was up-regulated in the baroreflex afferent pathway under similar experimental conditions, along with amelioration of reduced superoxide dismutase activity and increased superoxide in HFD rats. These results suggest that chronic treatment with fenofibrate plays a crucial role in the neural control of blood pressure by improving baroreflex afferent function due at least partially to PPAR-mediated up-regulation of UCP2 expression and reduction of oxidative stress.


Subject(s)
Afferent Pathways , Animals , Antihypertensive Agents , Pharmacology , Baroreflex , Blood Pressure , Fenofibrate , Pharmacology , Male , Oxidative Stress , PPAR gamma , Metabolism , Rats, Sprague-Dawley , Signal Transduction , Transcriptional Activation , Uncoupling Protein 2 , Metabolism , Up-Regulation
10.
Chinese Pharmaceutical Journal ; (24): 790-795, 2019.
Article in Chinese | WPRIM | ID: wpr-858001

ABSTRACT

OBJECTIVE: To study the effect of water-soluble materials on the inclusion complex of fenofibrate and hydroxypropyl-β-cyclodextrin. METHODS: The inclusion complex of fenofibrate/hydroxypropyl-β-cyclodextrin and the ternary system containing water-soluble materials were obtained by ball milling. The inclusion complex was characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (XRD), Fourier-transformed infrared spectrophotometry (FTIR), 1H-NMR spectroscopy, as well as in vitro dissolution and stability test. RESULTS: The stability tests and in vitro dissolution results showed that the addition of water-soluble materials could improve the stability constant and inclusion efficiency of the inclusion complex. Moreover, the addition of hydroxypropyl methylcellulose(HPMC) could result in a more stable complex and the in vitro dissolution rate of complex was also increased. CONCLUSION: The addition of appropriate water-soluble materials could enhance the inclusion efficiency of hydroxypropyl-β-cyclodextrin with drugs and form a more stable system.

11.
Article in Chinese | WPRIM | ID: wpr-796594

ABSTRACT

Diabetes is a worldwide prevalent disease and diabetic retinopathy (DR) is one of the common complications, which is vision threatening and even leading to blindness.The current management of DR includes laser retina photocoagulation, vitrectomy, and frequent intravitreal anti-vascular endothelial growth factor (VEGF) agents.However, these measures do not target the root cause and their efficacy is limited.Fenofibrate is a blood lipid lowering therapeutics and its metabolite, fenofibric acid, is responsible for the pharmacology effect.Two large clinical trials (FIELD and ACCORD-Eye) have demonstrated oral fenofibrate retarded progression of DR and the needs for laser retinopexy.The animal and cell researches have revealed that fenofibric acid attenuated overexpression of basement membrane and VEGF, protected the tight junctions of endothelial cells and vascular permeability, as well as inhibited cells migration and neovascularization via suppression of inflammatory cytokines.These pharmacological effects might be materialized through several pathways, such as PPAR-α, MAPK and nuclear factor-κB (NF-кB). Blood-ocular barrier is a significant limiting factor for therapeutics reaching retina after systemic administration.Local ocular application of fenofibric acid may achieve better efficacy through improving therapeutic concentration in the eye.This drug may be delivered either by eye drop formulation or a sustained delivery device under conjunctiva or sub-Tenon.

12.
Article in Chinese | WPRIM | ID: wpr-790169

ABSTRACT

Diabetes is a worldwide prevalent disease and diabetic retinopathy ( DR) is one of the common complications,which is vision threatening and even leading to blindness. The current management of DR includes laser retina photocoagulation,vitrectomy,and frequent intravitreal anti-vascular endothelial growth factor ( VEGF) agents. However,these measures do not target the root cause and their efficacy is limited. Fenofibrate is a blood lipid lowering therapeutics and its metabolite, fenofibric acid, is responsible for the pharmacology effect. Two large clinical trials ( FIELD and ACCORD-Eye) have demonstrated oral fenofibrate retarded progression of DR and the needs for laser retinopexy. The animal and cell researches have revealed that fenofibric acid attenuated overexpression of basement membrane and VEGF,protected the tight junctions of endothelial cells and vascular permeability,as well as inhibited cells migration and neovascularization via suppression of inflammatory cytokines. These pharmacological effects might be materialized through several pathways, such as PPAR-α, MAPK and nuclear factor-κB ( NF-кB ) . Blood-ocular barrier is a significant limiting factor for therapeutics reaching retina after systemic administration. Local ocular application of fenofibric acid may achieve better efficacy through improving therapeutic concentration in the eye. This drug may be delivered either by eye drop formulation or a sustained delivery device under conjunctiva or sub-Tenon.

13.
China Pharmacy ; (12): 2931-2936, 2019.
Article in Chinese | WPRIM | ID: wpr-817471

ABSTRACT

OBJECTIVE: To study the effects of bezafibrate (BEZ) and fenofibrate (FEN) on the proliferation of lung adenocarcinoma PC-9 cells and the expression of c-myc. METHODS: The effects of BEZ and FEN (12.5, 25, 50, 100, 200       μmol/L) on the survival rate of PC-9 cells were detected by CCK8 method. PC-9 cells were divided into administration group and control group. Administration group was given low, medium and high concentration (25, 50, 100 μmol/L) of BEZ and FEN; control group was treated with dimethyl sulfoxide for 48 h. Cell cycle distribution and apoptosis were detected by flow cytometry. qRT-PCR was used to detect mRNA relative expression of c-myc in cells. The protein relative expression of c-myc in cells were detected by Western blot assay. RESULTS: The survival rates of PC-9 cells were (80.76±3.2)%, (74.35±5.06)%, (62.8±1.23)%, (59.03±1.55)%, (39.8±1.01)% under the action of above concentration of BEZ; and the survival rates of PC-9 cells were (74.46±1.30)%, (61.91±4.77)%, (48.95±2.8)%, (37.05±1.55)%, (32.49±1.36)% under the action of FEN. Compared with control group, G1 phase cell ratio increased significantly in medium and high concentration groups of BEZ and FEN; the apoptotic rate of PC-9 cells was increased significantly in low, medium and high concentration groups of BEZ and FEN; mRNA and protein relative expression of c-myc were decreased significantly, with statistical significance (P<0.05). CONCLUSIONS: BEZ and FEN can inhibit the proliferation of PC-9 cells, and down-regulate c-myc expression.

14.
Article | IMSEAR | ID: sea-199906

ABSTRACT

Background: The objective of the study was to investigate the effect of fenofibrate on acute and subacute models of inflammation in adult male Wistar rats.Methods: After obtaining clearance from Institutional Animal Ethics Committee, six adult male Wistar rats were allocated to each of the three groups i.e. control, aspirin and fenofibrate. Acute inflammation was studied using carrageenan induced rat paw oedema and the volume displacement due to paw oedema was measured using the plethysmograph. Subacute inflammation was studied using foreign body insertion (cotton pellet and grass pith) models. Dry granuloma weight and histopathological examination of the granuloma were the outcome measures for measuring subacute inflammation. The percentage inhibition of inflammation with aspirin and fenofibrate was calculated in both acute and subacute models. The experiments were conducted according to the guidelines of the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA). The mean volume displacement obtained with a plethysmograph, the mean dry weight of granuloma and the percentage inhibition with aspirin and fenofibrate were analyzed by one way analysis of variance (ANOVA) using Graph pad prism software.Results: Aspirin and fenofibrate significantly reduced both acute and subacute inflammation (p<0.001). Dunnet’s test showed a significant difference in the study groups when compared to the control. The reduction of inflammation with fenofibrate was comparable to aspirin.Conclusions: Oral fenofibrate showed significant anti-inflammatory activity, which was comparable to aspirin, in both acute as well as sub-acute models of inflammation. This anti-inflammatory effect may benefit atherosclerosis in patients receiving fenofibrate for hyperlipidemia.

15.
Indian J Ophthalmol ; 2018 Jan; 66(1): 98-105
Article | IMSEAR | ID: sea-196545

ABSTRACT

Purpose: The purpose of this study is to study the benefit of addition of oral fenofibrate to the current regimen of diabetic macular edema (DME) management and quantify its effect on macular thickness and visual function in DME. Methods: Fifty-three eyes of 50 patients were randomized into treatment (Group A) (oral fenofibrate 160 mg/day) and control groups (Group B). Both groups underwent treatment of DME as per the standard treatment protocol of our hospital including intravitreal injections (anti-vascular endothelial growth factor/steroid) and grid laser. Patients were followed up every 2 months to note the visual acuity and central macular thickness (CMT) for 6 months. Results: Our groups were matched with respect to age (P = 0.802), mean diabetic age (P = 0.878), serum HbA1C levels (P = 0.523), and serum triglyceride levels (P = 0.793). The mean reduction in CMT was 136 ? in Group A and 83 ? in Group B at the end of 6 months. This difference was statistically significant (P = 0.031). Visual acuity improvement was 0.15 in Group A and 0.11 in Group B at the end of 6 months (P = 0.186). On subgroup analysis in Group A, we found that there was no difference in reduction of CMT between hypertensives and normotensives (P = 0.916), in patients with normal triglyceride levels and increased triglyceride levels (P = 0.975). Conclusion: Addition of fenofibrate to the standard protocol of DME management seems to facilitate reduction of CMT and probably have an added benefit on the visual functions.

16.
Laboratory Animal Research ; : 126-131, 2018.
Article in English | WPRIM | ID: wpr-717158

ABSTRACT

Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.


Subject(s)
Animals , Apolipoprotein C-III , Apoptosis , Diabetes Mellitus , Fenofibrate , Humans , Models, Animal , Peroxisome Proliferator-Activated Receptors , Polyphenols , Rats , Rats, Inbred BB , Wine
17.
International Eye Science ; (12): 2155-2159, 2018.
Article in Bislama | WPRIM | ID: wpr-688299

ABSTRACT

@#AIM: To explore the application effect of fenofibrate combined with 23G minimally invasive vitrectomy in patients with diabetic retinopathy(DR). <p>METHODS: Totally 102 DR patients(102 patients)treated in our hospital from October 2015 to November 2017 were selected and divided into observation group and control group according to random number table, 51 cases in each group. The 23G minimally invasive vitrectomy was performed in all patients. From the 1<sup>st</sup> day after operation, the two groups were treated with related treatment, and the control group was given conventional hypoglycemic, antihypertensive and improved microcirculation treatment. On the basis of the above, the observation group was treated with fenofibrate treatment. Both groups were treated for 3mo. The operation and postoperative basic conditions(operative time, intraoperative blood loss, complication rate, length of stay), the level of blood lipid \〖total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C)\〗, and the serum levels of related factors \〖lipoprotein associated phospholipase A2(Lp-PLA2), vascular endothelial growth factor(VEGF)\〗 before and after 3mo of operation of two groups were compared. Following up for 6mo after operation, the recurrence rate of two groups of retinopathy was statistically compared. <p>RESULTS: There was no significant difference in operative time, intraoperative blood loss, incidence of complications and length of stay between the two groups(<i>P</i>>0.05). There was no significant difference in the levels of TC, TG, LDL-C and HDL-C between the two groups before operation(<i>P</i>>0.05). After 3mo, the levels of TC, TG and LDL-C in the observation group were lower than those in the control group, and the level of HDL-C was higher than that in the control group, and the difference was statistically significant(<i>P</i><0.05). There was no significant difference in serum levels of Lp-PLA2 and VEGF between the two groups before operation(<i>P</i>>0.05). The serum levels of Lp-PLA2 and VEGF in the observation group were lower than those in the control group 3mo after operation, and the difference was statistically significant(<i>P</i><0.05). There was insignificant difference in visual function and quality of life, sensory adjustment, psychological and social scores and total scores between the two groups before surgery(<i>P</i>>0.05). At 3mo after operation, the scores of visual function and life quality in the observation group were lower than those in the control group, and the difference was statistically significant(<i>P</i><0.05). After follow-up for 6mo, no recurrence occurred in the observation group. The recurrence rate in the control group was 5.9%(3/51), and there was no significant difference between the two groups(<i>P</i>>0.05).<p>CONCLUSION: The combination of fenofibrate and 23G minimally invasive vitrectomy for the treatment of DR can effectively correct the disorder of lipid metabolism, reduce the level of serum Lp-PLA2 and VEGF, so it is beneficial to improve the visual function and quality of life of the patients, but there is no effective data support for reducing the postoperative recurrence rate.

18.
Article in Chinese | WPRIM | ID: wpr-710019

ABSTRACT

Objective To investigate the effect of fenofibrate on glucolipid metabolism and insulin sensitivity in lipoprotein lipase heterozygous knockout ( LPL+/-) mice, and to explore its mechanism. Methods LPL+/- mice and wild type ( WT) C57 mice were selected and divided into 3 groups ( n=6 each group):LPL+/-( FB) group, LPL+/-(W)group,andWTgroup.MiceinLPL+/-(FB)groupweregavagedwithfenofibrate(50mg·kg-1·d-1)for8 weeks. Mice in LPL+/-( W) and WT groups were orally fed with the same volume water as that in LPL+/-( FB) group for 8 weeks. Body weight was observed. Plasma triglyceride ( TG ) and free fatty acid ( FFA ) were measured. Intraperitoneal glucose tolerance test in 3 groups of mice were performed. The glucose area under the curve ( AUCG) and homeostasis model assessment for insulin resistance index ( HOMA-IR) were calculated. Insulin-stimulated Ser473 Akt phosphorylation in liver and skeletal muscle was measured by Western blot. Reactive oxygen species ( ROS) levels in liver and skeletal muscle were determined by dihydroethidium staining method and superoxide dismutase ( SOD) and catalase ( CAT) mRNA expression levels were detected by real-time PCR. Results Compared with LPL+/-( W) mice, body weight of LPL+/-( FB) mice was lowered, plasma TG and FFA levels were decreased by about 46.0%and 76.5%respectively, and fasting insulin level and HOMA-IR were decreased while there were no significant differences in fasting glucose level and AUCG between two groups. Insulin-stimulated Ser473 Akt phosphorylation levels in liver and skeletal muscle of LPL+/-mice were enhanced by fenofibrate. ROS level in skeletal muscle of LPL+/-( FB) mice was lower than that in LPL+/-( W) mice while there was no significant difference in ROS of liver between two groups. Fenofibrate significantly increased SOD and CAT mRNA expressions in skeletal muscle of LPL+/-mice, but not in liver. Conclusion Fenofibrate reduces body weight, ameliorates lipid metabolism, and improves insulin sensitivity in LPL+/- mice, with reduced oxidative stress.

19.
Article in English | WPRIM | ID: wpr-209180

ABSTRACT

OBJECTIVE: Previous studies have shown that fenofibrate therapy increases serum creatinine level and that there is a return of serum creatinine to baseline level after the discontinuation of the drug. We evaluated the effect of long-term fenofibrate therapy on creatinine levels and its reversibility in patients with hypertension and hypertriglyceridemia. METHODS: This retrospective study enrolled 54 hypertensive and hypertriglyceridemic patients taking fenofibrate for 3–6 years (Fenofibrate group) and 30 control patients with similar age, sex, follow-up duration, and creatinine levels (Control group). In 23 patients taking fenofibrate with low triglyceride level and/or with high creatinine levels, fenofibrate was discontinued, and creatinine levels were measured after 2 months. RESULTS: Creatinine levels increased in both the fenofibrate group (from 0.91±0.18 mg/dL to 1.09±0.23 mg/dL, p < 0.001) and the control group (from 0.94±0.16 mg/dL to 0.98±0.16 mg/dL, p=0.04) compared to baseline. However, the elevation was more pronounced in the fenofibrate group than in the control group (21.1±15.4% vs. 4.5±11.3%, p < 0.001). The discontinuation of fenofibrate lowered creatinine levels (from 1.39±0.32 mg/dL to 1.15±0.24 mg/dL, p < 0.001) which were still higher than pre-treatment levels (p=0.013). CONCLUSION: Long-term fenofibrate therapy significantly increased creatinine levels in hypertensive and hypertriglyceridemic patients. The effect of fenofibrate on creatinine level was partially reversible. This finding suggests that follow-up creatinine level is necessary with fenofibrate therapy.


Subject(s)
Creatinine , Fenofibrate , Follow-Up Studies , Humans , Hypertension , Hypertriglyceridemia , Retrospective Studies , Triglycerides
20.
Article in Chinese | WPRIM | ID: wpr-614320

ABSTRACT

Objective To study the curative efficacy of different doses of atorvastatin combined with fenofibrate in treatment of mixed type hyperlipidemia and its effects on blood lipid and prognosis.Methods 120 patients of mixed type hyperlipidemia who received therapy were selected as research subjects.According to random number table,the patients were divided into A group (n=60) and B group (n=60).The two groups were treated with atorvastatin and fenofibrate,the dose of atorvastatin in A group was 10mg,which in B group was 20mg,fenofibrate dose was 200mg.After 4 weeks of treatment,the therapeutic effect was compared.Results After treatment,the blood lipids of the two groups were improved(P0.05).The incidence rate of adverse reactions in A group was lower than that in B group[96.67%(58/60) vs.76.67%(46/60)](x2=6.171,P<0.05).Conclusion Low dose (10 mg) of atorvastatin combined with fenofibrate for mixed type hyperlipidemia has good lipid regulating effect,and adverse reaction is low,has little effect on the liver function of patients,which can effectively improve the prognosis,it is worthy of application and promotion.

SELECTION OF CITATIONS
SEARCH DETAIL