scholarly journals Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits

2019 ◽  
Vol 97 (7) ◽  
pp. 611-622 ◽  
Author(s):  
Mohammed M. Heikal ◽  
Ahmed A. Shaaban ◽  
Wagdi F. Elkashef ◽  
Tarek M. Ibrahim

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol (“bad” cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.

Author(s):  
Zhen-hong Xia ◽  
Wen-bo Chen ◽  
Li Shi ◽  
Xue Jiang ◽  
Ke Li ◽  
...  

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.


Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 271 ◽  
Author(s):  
Zhen-Hong Xia ◽  
Wen-Bo Chen ◽  
Li Shi ◽  
Xue Jiang ◽  
Ke Li ◽  
...  

Curcumin is the main secondary metabolite of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect of curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170–190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF + STZ group), and a high-fat diet combined with curcumin and STZ group (HF + Cur + STZ group). Compared with the HF + STZ group, the HF + Cur + STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST), and aspartate transaminase (ALT) levels, as well as liver coefficients. In the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.


2006 ◽  
Vol 291 (5) ◽  
pp. H2107-H2115 ◽  
Author(s):  
Nóra Erdei ◽  
Attila Tóth ◽  
Enikő T. Pásztor ◽  
Zoltán Papp ◽  
István Édes ◽  
...  

Obesity frequently leads to the development of hypertension. We hypothesized that high-fat diet (HFD)-induced obesity impairs the endothelium-dependent dilation of arterioles. Male Wistar rats were fed with normal (control) or HFD (60% of saturated fat, for 10 wk). In rats with HFD, body weight, mean arterial blood pressure, and serum insulin, cholesterol, and glucose were elevated. In isolated gracilis muscle arterioles (diameter: ∼160 μm) of HFD, rat dilations to ACh (at 1 μM, maximum: 83 ± 3%) and histamine (at 10 μM, maximum: 16 ± 4%) were significantly ( P < 0.05) decreased compared with those of control responses (maximum: 90 ± 2 and 46 ± 4%, respectively). Dilations to the NO donor sodium nitroprusside were similar in the two groups. Inhibition of NO synthesis by Nω-nitro-l-arginine methyl ester reduced ACh- and histamine-induced dilations in control arterioles but had no effect on microvessels of HFD rats. The superoxide dismutase mimetic Tiron or xanthine oxidase inhibitor allopurinol enhanced ACh (maximum: 90 ± 2 and 93 ± 2%, respectively)- and histamine (maximum: 30 ± 7 and 37 ± 8%, respectively)-induced dilations in HFD arterioles, whereas the NAD(P)H oxidase inhibitor apocynin had no significant effect. Correspondingly, in carotid arteries of HFD rats, an enhanced superoxide production was shown by lucigenin-enhanced chemiluminescence, in association with an increased xanthine oxidase, but not NAD(P)H oxidase activity. In addition, a marked xanthine oxidase immunostaining was detected in the endothelial layer of the gracilis arterioles of HFD, but not in control rats. These findings suggest that, in obese rats, NO mediation of endothelium-dependent dilation of skeletal muscle arterioles is reduced because of an enhanced xanthine oxidase-derived superoxide production. These alterations demonstrate substantial dysregulation of arteriolar tone by the endothelium in HFD-induced obesity, which may contribute to disturbed tissue blood flow and development of increased peripheral resistance.


2023 ◽  
Vol 83 ◽  
Author(s):  
A. M. Mousa ◽  
M. E. Taha ◽  
SH. M. ELdeighdye ◽  
A. M. Kamal

Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Qishu Zhou ◽  
Chunyu Liang ◽  
Yafei Li ◽  
Yi Yan

Objective  To investigate the effect of one-time high-intensity intermittent exercise in white fat autophagy in obese rats and provide a theoretical basis of the molecular mechanism of exercise fat loss. Methods  Eighteen male 3-weeks-old rats were selected and divided into control group fed with normal diet (C), high-fat diet group fed with high fat diet (H). After 16 weeks, there were twelve obesity rats that divided into diet group (HS) and exercise group (HE). The other six control group rats of 19 weeks age were used as the standard (CS group). OE group did the high intensity intermittent exercise once. The CS group and the CS group were kept quietly. Three groups were taken subcutaneous white adipose tissue(S) and epididymal white adipose tissue (E) immediately after exercise. Mensurate the expression of LC3 gene in the tissue using the fluorescent quantitative PCR. Results 1. The expression of LC3 mRNA from white fat tissue was different to the tissues, which the expression of epididymal white adipose tissue of each group was higher than that in subcutaneous white adipose tissue (P <0.01). 2. Compared with CS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.01) and the expression of the subcutaneous white adipose tissue increased from HS group (P <0.05). 3. Compared with OS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.05) and the expression of subcutaneous white adipose tissue decreased from OS group. Conclusions The expression of LC3mRNA in epididymal white fat adipose tissue of rats was significantly higher than that of subcutaneous white fat. The changes of LC3mRNA expression of adipose tissue caused by high-fat diet have tissue differences. One-time high-intensity intermittent exercise can reduce the expression of LC3mRNA in fat tissue of obese rats. Its regulatory mechanism needs to be further studied.


Author(s):  
Pascal Richette

The general goals of gout therapy are to manage acute flares and to prevent recurrences and prevent or reverse the complications of urate deposition by lowering urate levels. The choice of drug should be made on the basis of the patient’s co-morbidities, other medications, and side effect profile. Treatment of flares can be achieved with non-steroidal anti-inflammatory drugs, colchicine, or corticosteroids (systemic or intra-articular). Interleukin-1 blockers could become an alternative in patients contraindicated for traditional anti-inflammatory agents. Lowering of urate levels below monosodium urate (MSU) saturation point with both a non-pharmacological and pharmacological approach allows to dissolve MSU crystals and to cure gout. Serum urate (SUA) levels should be maintained below 6 mg/dL (360 μ‎mol/L) or below 5 mg/dL (300 μ‎mol/L) in patients with severe gout to facilitate faster dissolution of crystals. Urate-lowering therapy (ULT) should be initiated close to the first diagnosis of gout. Allopurinol and febuxostat are the most widely used xanthine oxidase inhibitors to lower SUA levels. If the SUA target cannot be reached by these agents, uricosurics are indicated, either alone or in combination with a xanthine oxidase inhibitor. In patients with severe tophaceous gout in whom the SUA target cannot be reached with any other available drug, pegloticase is indicated. Since ULT initiation may trigger acute attacks of gout, prophylaxis with an anti-inflammatory agent is recommended, mostly with low-dose colchicine. Of note, patient education, appropriate lifestyle advice, and treatment of comorbidities are also important parts of the management of patients with gout.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
O. B. Ibitoye ◽  
U. M. Ghali ◽  
J. B. Adekunle ◽  
J. N. Uwazie ◽  
T. O. Ajiboye

Dioscoreophyllum cumminsii (Stapf) Diels leaves are widely used in the treatment of diabetes, obesity, and cardiovascular related complications in Nigeria. This study investigates the anti-inflammatory and antiobesity effect of aqueous extract of Dioscoreophyllum cumminsii leaves in high-fat diet- (HFD-) induced obese rats. HFD-fed rats were given 100, 200, and 400 mgkg−1 body weight of aqueous extract of Dioscoreophyllum cumminsii leaves for 4 weeks starting from 9th week of HFD treatment. D. cumminsii leaves aqueous extract reversed HFD-mediated decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase. Moreover, HFD-mediated elevation in the levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl, and DNA fragmentation in rats liver was lowered. HFD-mediated alterations in serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were significantly reversed by the extract. The treatment of HFD-fed rats reduced the levels of insulin, leptin, protein carbonyl, fragmented DNA, and tumour necrosis factor-α and interleukin- (IL-) 6 and IL- 8 and increased the adiponectin level. This study showed that aqueous extract of Dioscoreophyllum cumminsii leaves has potential antiobesity and anti-inflammatory effects through modulation of obesity-induced inflammation, oxidative stress, and obesity-related disorder in HFD-induced obese rats.


2008 ◽  
Vol 176 (2-3) ◽  
pp. 137-142 ◽  
Author(s):  
Xiaoyu Liu ◽  
Ruohua Chen ◽  
Yanjun Shang ◽  
Binghua Jiao ◽  
Caiguo Huang

1968 ◽  
Vol 42 (4) ◽  
pp. 489-494 ◽  
Author(s):  
E. BLÁZQUEZ ◽  
C. LOPEZ QUIJADA

SUMMARY The influence of the diet on the levels of insulin was studied in rats on a high-fat diet. Plasma and glucose insulin concentrations of a control group and of rats on a high-fat diet were compared, and so was the insulin concentration in the pancreas of the two groups. The mean plasma insulin concentration in the control group was 40 μ-u./ml. and that of insulin extracted from the pancreas was 2·5 μg./100 mg. tissue; plasma glucose was 156 mg./100 ml. The animals fed on a high-fat diet showed diabetic features. The mean plasma insulin level was 9 μ-u./ml., and plasma glucose increased to 210 mg./100 ml. The insulin concentration in the pancreas was not significantly different from that in the controls. In vitro the epididymal fat and the diaphragm of the high-fat-diet group were less sensitive to insulin than the same tissues in the control group.


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