Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

AbstractIntroductionHypercholesterolemia is a major risk factor for the development of atherosclerosis and endothelial dysfunction. Chelating agents may play a modulatory role in atherosclerosis by removal of calcium from atherosclerotic plaques.AimThe present study aimed to explore the effects of calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) on diet-induced hypercholesterolemia in rats using simvastatin as a reference standard.MethodsHypercholesterolemia was induced by feeding rats with cholesterol-rich diet for six weeks. Rats were divided into five groups (n=8): normal control, hypercholesterolemic control, simvastatin (20mg/kg; p.o.), CaNa2EDTA (100mg/kg; i.p.) and DMSA (100mg/kg; i.p.). Treatments continued daily for the six weeks of diet feeding.ResultsDiet-induced hypercholesterolemia resulted in alterations in the lipid profile markers and a state of oxidative stress coupled by compensatory increase in serum nitric oxide (NO) level and decreased aortic endothelial nitric oxide synthase (eNOS) activity parallel to increased inducible nitric oxide synthase (iNOS) activity, aortic calcium content and aortic wall thickness. Treatment with simvastatin, CaNa2EDTA and DMSA improved lipid profile and oxidative stress markers. In addition, they attenuated hypercholesterolemia-induced changes in serum NO level, aortic eNOS and iNOS activities, calcium content and aortic wall thickness.ConclusionPretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties

Biochemical and Genetical Evaluation of Pomegranate Impact on Diabetes Mellitus Induced by Alloxan in Female Rats

Abstract: Various food industries explored the possibility of developing a nutritional supplement rich in natural antioxidants from pomegranates. This study has focused on the ability of pomegranate peel and juice to study the antioxidant status. Thirty two rats were allocated in 4 groups as follows: GroupI; control group without any treatment; GroupII: diabetic animals injected with alloxan; Group III: diabetic peel group animals injected with alloxan and then feed on peel pomegranate; GroupIV: diabetic juice group animals injected with alloxan and then gavage with pomegranate juice. After 4 weeks of treatment biochemical analysis were measured such as glucose, insulin, alpha-amylase, lipid profile (cholesterol, triglyceride HDL, LDL and total lipids), total protein, homocysteine, total antioxidant capacity and liver enzymes (AST&ALT). In addition, pancreas and liver tissues were separated for genetic analysis in which pancreatic tissues were used for RAPD-PCR analysis and liver tissues for DNA fragmentation assay. Results showed significant increase in glucose and alpha amylase levels in diabetic group, while insulin decreased. Peel and juice of pomegranate ameliorates this effect and decreased glucose, alpha amylase while insulin level increased. Cholesterol, triglycerides, LDL and total lipids increased while HDL decreased in diabetic group. Peel and juice of pomegranate prevented these changes. The more pronounced effect appeared in group III treated with peel pomegranate. Total protein was not affected by alloxan or pomegranate. Homocysteine was significantly increased while total antioxidant capacity decreased in diabetic group. After treatment by pomegranate peel and juice, these parameters become near to the control values. AST and ALT were significantly increased in diabetic group. But after treatment with peel and juice, AST and ALT levels decreased and become near to the control level especially ALT value. Furthermore, rate of DNA fragmentation and DNA band polymorphism increased significantly in diabetic group. While after treatment by peel and juice rate of DNA band polymorphism and DNA fragmentation were decreased significantly. Pomegranate peel and juice showed significant reduction in LDL oxidative susceptibility and an increase in total antioxidant status. Pomegranate is able to reduce the progression in atherosclerosis. The antioxidant content in foods decreased the oxidative stress related diseases

SULPHATED POLYSACCHARIDES (SPS) FROM THE GREEN ALGA ULVA FASCIATA EXTRACT MODULATES LIVER AND KIDNEY FUNCTION IN HIGH FAT DIET-INDUCED HYPERCHOLESTEROLEMIC RATS

Objective: Hypercholesterolemia (HC) was frequently associated with oxidative stress, and release of inflammatory cytokines is to determine the hypolipidemic effects of sulphated polysaccharides from seaweed Ulva fasciata algal extracts through measuring the activities of some parameters related to liver and kidney functions in the serum of hypercholesterolemic rats as compared to normal one.Methods: Different groups of rats were administered a high cholesterol diet. Liver and kidney functions, inflammatory cytokines (TNF-α, CRP, MPO and IL-10), oxidative stress (GSH, MDA and NO), in addition to cell adhesion molecules (ICAM-1 and VCAM-1) were assessed before and after treatment with the algal polysaccharides. In addition, histological examination of liver and kidney were performed to confirm the biochemical findings.Results: The obtained results showed that oxidative stress and inflammatory markers associated with hypercholesterolemia were significantly increased in HC-rats. The histopathological examination of liver and kidney demonstrated severe degeneration with diffuse vacuolar degeneration, necrosis and the presence of fatty droplets. In addition; nephron-histological examination revealed, mild glomerular injury with mild vascular and inflammatory changes. Treatment with the algal sulphated polysaccharides effectively improved these disorders and diminished the formation of fatty liver, as well as renal dysfunction more than the reference drug; fluvastatin. Conclusion: It could be concluded that the consumption of UFP (Ulva fasciata polysaccharides), may be associated with attenuation of inflammatory markers, amelioration of fatty liver and improvement of renal dysfunction, that in turn lead to counteract hypercholesterolemia and its related disorders; such as obesity, and heart disease.Keywords: Non-alcoholic fatty liver disease, Seaweed, Ulva fasciata, Hypercholesterolemia, Hypolipidemic activity, Sulphated polysaccharides (SPs

An Electroactive Oligo-EDOT Platform for Neural Tissue Engineering

The unique electrochemical properties of the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties in processing and lack of biodegradability have hindered progress in this field. Here, the functionality of PEDOT:PSS for neural tissue engineering is improved by incorporating 3,4-ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end-capping strategy, into block co-polymers. By exploiting end-functionalized oligoEDOT constructs as macroinitiators for the polymerization of poly(caprolactone), a block co-polymer is produced that is electroactive, processable, and bio-compatible. By combining these properties, electroactive fibrous mats are produced for neuronal culture via solution electrospinning and melt electrospinning writing. Importantly, it is also shown that neurite length and branching of neural stem cells can be enhanced on the materials under electrical stimulation, demonstrating the promise of these scaffolds for neural tissue engineering

Development and validation of a repharsed phase- HPLC method for simultaneous determination of rosiglitazone and glimepiride in combined dosage forms and human plasma

<p>Abstract</p> <p>Background</p> <p>Rosiglitazone (ROZ) and glimepiride (GLM) are antidiabetic agents used in the treatment of type 2 diabetes mellitus. A survey of the literature reveals that only one spectrophotometric method has been reported for the simultaneous determination of ROS and GLM in pharmaceutical preparations. However the reported method suffers from the low sensitivity, for this reason, our target was to develop a simple sensitive HPLC method for the simultaneous determination of ROZ and GLM in their combined dosage forms and plasma.</p> <p>Results</p> <p>A simple reversed phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the simultaneous determination of Rosiglitazone (ROS) and Glimepiride (GLM) in combined dosage forms and human plasma. The separation was achieved using a 150 mm × 4.6 mm i.d., 5 μm particle size Symmetry^®C18 column. Mobile phase containing a mixture of acetonitrile and 0.02 M phosphate buffer of pH 5 (60: 40, V/V) was pumped at a flow rate of 1 mL/min. UV detection was performed at 235 nm using nicardipine as an internal standard. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The developed and validated method was successfully used for quantitative analysis of Avandaryl™ tablets. The chromatographic analysis time was approximately 7 min per sample with complete resolution of ROS (t_R= 3.7 min.), GLM (t_R= 4.66 min.), and nicardipine (t_R, 6.37 min). Validation studieswas performed according to ICH Guidelines revealed that the proposed method is specific, rapid, reliable and reproducible. The calibration plots were linear over the concentration ranges 0.10-25 μg/mL and 0.125-12.5 μg/mL with LOD of 0.04 μg/mL for both compounds and limits of quantification 0.13 and 0.11 μg/mL for ROS and GLM respectively.</p> <p>Conclusion</p> <p>The suggested method was successfully applied for the simultaneous analysis of the studied drugs in their co-formulated tablets and human plasma. The mean percentage recoveries in Avandaryl™ tablets were 100.88 ± 1.14 and 100.31 ± 1.93 for ROS and GLM respectively. Statistical comparison of the results with those of the reference method revealed good agreement and proved that there were no significant difference in the accuracy and precision between the two methods respectively. The interference likely to be introduced from some co-administered drugs such as glibenclamide, gliclazide, metformine, pioglitazone and nateglinide was investigated.</p

Biological performance of a promising Kefiran-biopolymer with potential in regenerative medicine applications: a comparative study with hyaluronic acid

Kefiran from kefir grains, an exopolysaccharide (EPS) produced by lactic acid bacteria (LAB), has received an increasing interest because of its safe status. This natural biopolymer is a water-soluble glucogalactan with probed health-promoting properties. However, its biological performance has yet to be completely recognized and properly exploited. This research was carried out to evaluate the in vitro antioxidant and the in vitro anti-inflammatory properties of Kefiran biopolymer. Regarding antioxidant activity, the results demonstrated that the Kefiran extract possessed the strongest reducing power and superoxide radical scavenging, over hyaluronic acid (HA, gold standard viscosupplementation treatment). This exopolysaccharide showed a distinct antioxidant performance in the majority of in vitro working mechanisms of antioxidant activity comparing to HA. Moreover, Kefiran presented an interesting capacity to scavenge nitric oxide radical comparing to the gold standard that did not present any potency. Finally, the cytotoxic effects of Kefiran extracts on hASCs were also performed and demonstrated no cytotoxic response, ability to improve cellular function of hASCs. This study demonstrated that Kefiran represented a great scavenger for reactive oxygen and nitrogen species and showed also that it could be an excellent candidate to promote tissue repair and regeneration.Hajer Radhouani, Cristiana Gonçalves and F. Raquel Maia were supported by grants with reference SFRH/BPD/100957/2014, SFRH/BPD/94277/2013 and SFRH/BPD/117492/2016, respectively of Fundação para a Ciência e a Tecnologia (FCT) from Portugal. JM Oliveira also would like to thank FCT for the fund provided under the program Investigador FCT 2015 (IF/01285/2015).info:eu-repo/semantics/publishedVersio