Comparative study on antioxidant effects and vascular matrix metalloproteinase-2 downregulation by dihydropyridines in renovascular hypertension

The vascular remodeling associated with hypertension involves oxidative stress and enhanced matrix metalloproteinases (MMPs) expression/activity, especially MMP-2. While previous work showed that lercanidipine, a third-generation dihydropyridine calcium channel blocker (CCB), attenuated the oxidative stress and increased MMP-2 expression/activity in two-kidney, one-clip (2K1C) hypertension, no previous study has examined whether first- or second-generation dihydropyridines produce similar effects. We compared the effects of nifedipine, nimodipine, and amlodipine on 2K1C hypertension-induced changes in systolic blood pressure (SBP), vascular remodeling, oxidative stress, and MMPs levels/activity. Sham-operated and 2K1C rats were treated with water, nifedipine 10 mg/kg/day, nimodipine 15 mg/kg/day, or amlodipine 10 mg/kg/day by gavage, starting 3 weeks after hypertension was induced. SBP was monitored weekly. After 6 weeks of treatment, quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin-stained sections. Aortic and systemic reactive oxygen species levels were measured by using dihydroethidine and thiobarbituric acid-reactive substances (TBARs), respectively. Aortic MMP-2 levels and activity were determined by gelatin zymography, in situ zymography, and immunofluorescence. Nifedipine, nimodipine, or amlodipine attenuated the increases in SBP in hypertensive rats by approximately 17% (P<0.05) and prevented vascular hypertrophy (P<0.05). These CCBs blunted 2K1C-induced increases in vascular oxidative stress and plasma TBARs concentrations (P<0.05). All dihydropyridines attenuated the increases in aortic MMP-2 levels and activity associated with 2K1C hypertension. These findings suggest lack of superiority of one particular dihydropyridine, at least with respect to antioxidant effects, MMPs downregulation, and inhibition of vascular remodeling in hypertension.

Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension

Background and purpose: Increased oxidative stress and up-regulation of matrix metalloproteinases (MMPs) may cause structural and functional vascular changes in renovascular hypertension. We examined whether treatment with spironolactone (SPRL), hydrochlorothiazide (HCTZ) or both drugs together modified hypertension-induced changes in arterial blood pressure, aortic remodelling, vascular reactivity, oxidative stress and MMP levels and activity, in a model of renovascular hypertension. Experimental approach: We used the two-kidney,one-clip (2K1C) model of hypertension in Wistar rats. Sham-operated or hypertensive rats were treated with vehicle, SPRL (25 mg center dot kg-1 center dot day-1), HCTZ (20 mg center dot kg-1 center dot day-1) or a combination for 8 weeks. Systolic blood pressure was monitored weekly. Aortic rings were isolated to assess endothelium-dependent and -independent relaxations. Morphometry of the vascular wall was carried out in sections of aorta. Aortic NADPH oxidase activity and superoxide production were evaluated. Formation of reactive oxygen species was measured in plasma as thiobarbituric acid-reactive substances. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry and immunohistochemistry. Key results: Treatment with SPRL, HCTZ or the combination attenuated 2K1C-induced hypertension, and reversed the endothelial dysfunction in 2K1C rats. Both drugs or the combination reversed vascular aortic remodelling induced by hypertension, attenuated hypertension-induced increases in oxidative stress and reduced MMP-2 levels and activity. Conclusions and implications: SPRL or HCTZ, alone or combined, exerted antioxidant effects, and decreased renovascular hypertension-induced MMP-2 up-regulation, thus improving the vascular dysfunction and remodelling found in this model of hypertension.

Antioxidant effects of ryegrass phenolics in lamb liver and plasma

Sixteen lambs were divided into two groups and fed two different diets. Eight lambs were stall-fed with a concentrate-based diet (C), and the remaining eight lambs were allowed to graze on Lolium perenne (G). The antioxidant status was measured in the liver and plasma samples before and after solid-phase extraction (SPE) to probe the antioxidant effects that grass phenolic compounds may have conferred onto the animal tissues. The liver and plasma samples from grass-fed lambs displayed a greater antioxidant capacity than the tissues from C lamb group, but only if samples had not been passed through SPE cartridges. Finally, the feed and animal tissues, which had been purified by SPE, were analysed by liquid chromatography combined with mass spectrometry (LC-MS) to identify phenolic compounds present in L. perenne and to evaluate the results from the antioxidant assays. It would appear that the improvement of the antioxidant capacity of lamb liver and plasma from lambs fed ryegrass was not related to the direct transfer of phenolic compounds from grass to the animal tissues.

Hypoglycaemic and antioxidant effects of onion, Allium cepa: dietary onion addition, antioxidant activity and hypoglycaemic effects on diabetic rats

The purpose of the present study was to discover the relative potency of onion, Allium cepa, with respect to its hypoglycaemic and hypolipidaemic effects on the diabetic situation, and the association of these effects with the potential against oxidative stress. Male Wistar rats were divided into four groups. A normal control ( group A), and a non-diabetic group ( group B) were treated daily with 1 ml A. cepa solution (0.4 g A. cepa/rat). Groups C and D were made diabetic by an intraperitoneal injection of streptozotocin (STZ) ( 60 mg/kg body weight) in citrate buffer ( pH 6.3). These animals ( groups C and D) were the STZ diabetic control and STZ diabetic rats with onion intake, respectively. Onion increased the fasting serum high-density lipoprotein levels, and demonstrated alleviation of hyperglycaemia in STZ diabetic rats. The hypoglycaemic and hypolipidaemic actions of A. cepa were associated with antioxidant activity, since onion decreased superoxide dismutase activities while no increased lipid hydroperoxide and lipoperoxide concentrations were observed in diabetic rats treated with A. cepa.

Photoprotective and antioxidant effects of Rhubarb: Inhibitory action on tyrosinase and tyrosine kinase activities and TNF-α, IL-1α and α-MSH production in human melanocytes

Background: Exposure to ultraviolet (UV) radiation causes various forms of acute and chronic skin damage, including immunosuppression, inflammation, premature aging and photodamage. Furthermore, it induces the generation of reactive oxygen species, produces proinflammatory cytokines and melanocyte-stimulating hormone (MSH) and increases tyrosinase activity. The aim of this study was to evaluate the potential photoprotective effects of Rheum rhaponticum L. rhizome extract on human UV-stimulated melanocytes.Methods: The effects of Rheum rhaponticum rhizome extract on tyrosine kinase activity, and on interleukin-1α (IL-1α), tumour necrosis factor α (TNF-α), and α-MSH production in human epidermal melanocytes were evaluated under UV-stimulated and non-stimulated conditions. Antioxidant activity was evaluated by lipid peroxidation and 1,1-dyphenyl-2-picryl-hydrazyl (DPPH) assays, while anti-tyrosinase activity was evaluated by the mushroom tyrosinase method.Results: Rheum rhaponticum L. rhizome extract showed in vitro antioxidant properties against lipid peroxidation, free radical scavenging and anti-tyrosinase activities, and inhibited the production of IL-1α, TNF-α, α-MSH, and tyrosine kinase activity in melanocytes subjected to UV radiation.Conclusions: These results support the inclusion of Rheum rhaponticum L. rhizome extract into cosmetic, sunscreen and skin care products for the prevention or reduction of photodamage. © 2013 Silveira et al; licensee BioMed Central Ltd.

Antioxidant effects of quercetin and naringenin are associated with impaired neutrophil microbicidal activity

Naringenin and quercetin are considered antioxidant compounds with promising activity against oxidative damage in human cells. However, no reports have described their effects on reactive oxygen species (ROS) production by phagocytes during microbicidal activity. Thus, the present study evaluated the effects of naringenin and quercetin on ROS production, specifically hypochlorous acid (HOCl), and their involvement in the microbicidal activity of neutrophils. Naringenin and quercetin inhibited HOCl production through different systems, but this inhibition was more pronounced for quercetin, even in the cell-free systems. With regard to the microbicidal activity of neutrophils, both naringenin and quercetin completely inhibited the killing of Staphylococcus aureus. Altogether, these data indicate that the decrease in the oxidant activity of neutrophils induced by these compounds directly impaired the microbicidal activity of neutrophils. Naringenin and quercetin exerted their effects by controlling the effector mechanisms of ROS production, with both positive and negative effects of these antioxidant agents in oxidative stress conditions and on ROS in the microbicidal activity of phagocytes. The present results challenge the traditional view of antioxidants as improvers of pathological conditions. © 2013 Francielli de Cássia Yukari Nishimura et al.

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension

Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats. Sham-operated and 2K1C rats were treated with vehicle or sodium nitrite (15 mg/kg/day) for 4 weeks. We evaluated the effects induced by sodium nitrite treatment on systolic blood pressure (SBP) and NO markers such as plasma nitrite, nitrite + nitrate (NOx), cGMP, and blood levels of nitrosyl-hemoglobin. In addition, we also evaluated effects of nitrite on oxidative stress and antioxidant enzymes. Dihydroethidium (DHE) was used to evaluate aortic reactive oxygen species (ROS) production by fluorescence microscopy, and plasma levels of thiobarbituric acid-reactive species (TBARS) were measured in plasma samples from all experimental groups. Red blood cell superoxide dismutase (SOD) and catalase activity were evaluated with commercial kits. Sodium nitrite treatment reduced SBP in 2K1C rats (P < 0.05). We found lower plasma nitrite and NOx levels in 2K1C rats compared with normotensive controls (both P < 0.05). Nitrite treatment restored the lower levels of nitrite and NOx. While no change was found in the blood levels of nitrosyl-hemoglobin (P > 0.05), nitrite treatment increased the plasma levels of cGMP in 2K1C rats (P < 0.05). Higher plasma TBARS levels and aortic ROS levels were found in hypertensive rats compared with controls (P < 0.05), and nitrite blunted these alterations. Lower SOD and catalase activities were found in 2K1C hypertensive rats compared with controls (both P < 0.05). Nitrite treatment restored SOD activity (P < 0.05), whereas catalase was not affected. These data suggest that even a single daily oral dose of sodium nitrite is able to lower SBP and exert antioxidant effects in renovascular hypertension.

Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles

Polymeric nanoparticles (PLGA) have been developed for the encapsulation and controlled release of quercetin and catechin. Nanoparticles were fabricated using a solvent displacementmethod. Physicochemical properties were measured by light scattering, scanning electron microscopy and zeta-potential, X-ray diffraction, infrared spectroscopy and differential scanning calorimetry. Encapsulation efficiency and in vitro release profiles were obtained from differential pulse voltammetry experiments. Antioxidant properties of free and encapsulated flavonoids were determined by TBARS, fluorescence spectroscopy and standard chelating activity methods. Relatively small (d approximate to 400 nm) polymeric nanoparticles were obtained containing quercetin or catechin in a non-crystalline form (EE approximate to 79%) and the main interactions between the polymer and each flavonoid were found to consist of hydrogen bonds. In vitro release profiles were pH-dependant, the more acidic pH, the faster release of each flavonoid from the polymeric nanoparticles. The inhibition of the action of free radicals and chelating properties, were also enhanced when quercetin and catechin were encapsulated within PLGA nanoparticles. The information obtained from this study will facilitate the design and fabrication of polymeric nanoparticles as possible oral delivery systems for encapsulation, protection and controlled release of flavonoids aimed to prevent oxidative stress in human body or food products.

Ceratonia siliqua L. hydroethanolic extract obtained by ultrasonication: antioxidant activity, phenolic compounds profile and effects in yogurts functionalized with their free and microencapsulated forms

Bioactive extracts were obtained from powdered carob pulp through an ultrasound extraction process and then evaluated in terms of antioxidant activity. Ten minutes of ultrasonication at 375 Hz were the optimal conditions leading to an extract with the highest antioxidant effects. After its chemical characterization, which revealed the preponderance of gallotannins, the extract (free and microencapsulated) was incorporated in yogurts. The microspheres were prepared using an extract/sodium alginate ratio of 100/400 (mg mg(-1)) selected after testing different ratios. The yogurts with the free extract exhibited higher antioxidant activity than the samples added with the encapsulated extracts, showing the preserving role of alginate as a coating material. None of the forms significantly altered the yogurt's nutritional value. This study confirmed the efficiency of microencapsulation to stabilize functional ingredients in food matrices maintaining almost the structural integrity of polyphenols extracted from carob pulp and furthermore improving the antioxidant potency of the final product.

Lutein improves antioxidant defense in vivo and protects against DNA damage and chromosome instability induced by cisplatin

Lutein (LT) is the second most prevalent carotenoid in human serum, and it is abundantly present in dark, leafy green vegetables. The objectives of this study were to evaluate the genotoxicity and mutagenicity of LT, and its protective effects in vivo against DNA damage and chromosome instability induced by cisplatin (cDDP). For this purpose, we used the comet assay and micronucleus (MN) test, and we evaluated the antioxidant effects of LT by determination of enzymatic (catalase-CAT) and non-enzymatic (reduced glutathione-GSH) activity. Mice were divided into six groups: cDDP, mineral oil (OM), LT groups and LT + cDDP groups. To perform the MN test on peripheral blood (PB) cells, blood samples were collected before the first treatment (T0), and 36 h (T1) and 14 days (T2) after the first treatment. To perform the comet assay, blood samples were collected 4 h after the first and the last treatment. Oxidative capacity was analyzed in total blood that was collected 24 h after the last treatment, when bone marrow (BM) sample was also collected for the MN test. No genotoxic or mutagenic effects of LT were observed for the doses evaluated. We did find that this carotenoid was able to reduce the formation of crosslinks and chromosome instability induced by cDDP. No differences were observed in CAT levels, and LT treatment increased GSH levels compared with a negative control group, reinforcing the role of this carotenoid as an antioxidant.

Sodium nitrite downregulates vascular NADPH oxidase and exerts antihypertensive effects in hypertension

Dietary nitrite and nitrate are important sources of nitric oxide (NO). However, the use of nitrite as an antihypertensive drug may be limited by increased oxidative stress associated with hypertension. We evaluated the antihypertensive effects of sodium nitrite given in drinking water for 4 weeks in two-kidney one-clip (21(1 C) hypertensive rats and the effects induced by nitrite on NO bioavailability and oxidative stress. We found that, even under the increased oxidative stress conditions present in 2K1C hypertension, nitrite reduced systolic blood pressure in a dose-dependent manner. Whereas treatment with nitrite did not significantly change plasma nitrite concentrations in 2K1C rats, it increased plasma nitrate levels significantly. Surprisingly, nitrite treatment exerted antioxidant effects in both hypertensive and sham-normotensive control rats. A series of in vitro experiments was carried out to show that the antioxidant effects induced by nitrite do not involve direct antioxidant effects or xanthine oxidase activity inhibition. Conversely, nitrite decreased vascular NADPH oxidase activity. Taken together, our results show for the first time that nitrite has antihypertensive effects in 2K1C hypertensive rats, which may be due to its antioxidant properties resulting from vascular NADPH oxidase activity inhibition. (C) 2011 Elsevier Inc. All rights reserved.

Hemodynamic effects of inducible nitric oxide synthase inhibition combined with sildenafil during acute pulmonary embolism

While endogenous nitric oxide (NO) may be relevant to the beneficial hemodynamic effects produced by sildenafil during acute pulmonary embolism (APE), huge amounts of inducible NO synthase (iNOS)derived NO may contribute to lung injury. We hypothesized that iNOS inhibition with S-methylisothiourea could attenuate APE-induced increases in oxidative stress and pulmonary hypertension and, therefore, could improve the beneficial hemodynamic and antioxidant effects produced by sildenafil during APE. Hemodynamic evaluations were performed in non-embolized dogs treated with saline (n = 4), S-methylisothiourea (0.01 mg/kg followed by 0.5 mg/kg/h, n = 4), sildenafil (0.3 mg/kg, n = 4), or S-methylisothiourea followed by sildenafil (n = 4), and in dogs that received the same drugs and were embolized with silicon microspheres (n = 8 for each group). Plasma nitrite/nitrate (NOx) and thiobarbituric acid reactive substances (TBARS) concentrations were determined by Griess and a fluorometric assay, respectively. APE increased mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) by 25 +/- 1.7 mm Hg and by 941 +/- 34 dyn s cm(-5) m(-2), respectively. S-methylisothiourea neither attenuated APE-induced pulmonary hypertension, nor enhanced the beneficial hemodynamic effects produced by sildenafil after APE (>50% reduction in pulmonary vascular resistance). While sildenafil produced no change in plasma NOx concentrations, S-methylisothiourea alone or combined with sildenafil blunted APE-induced increases in NOx concentrations. Both drugs, either alone or combined, produced antioxidant effects. In conclusion, although iNOS-derived NO may play a key role in APE-induced oxidative stress, our results suggest that the iNOS inhibitor S-methylisothiourea neither attenuates APE-induced pulmonary hypertension, nor enhances the beneficial hemodynamic effects produced by sildenafil. (C) 2010 Elsevier Inc. All rights reserved.

Neuronal activity controls the antagonistic between PGC-1α and SMRT in regulating antioxidant defences

Transcriptional coactivators and corepressors often have multiple targets and can have opposing actions on transcription and downstream physiological events. The coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is under-expressed in Huntington's disease and is a regulator of antioxidant defenses and mitochondrial biogenesis. We show that in primary cortical neurons, expression of PGC-1α strongly promotes resistance to excitotoxic and oxidative stress in a cell autonomous manner, whereas knockdown increases sensitivity. In contrast, the transcriptional corepressor silencing mediator of retinoic acid and thyroid hormone receptors (SMRT) specifically antagonizes PGC-1α-mediated antioxidant effects. The antagonistic balance between PGC-1α and SMRT is upset in favor of PGC-1α by synaptic activity. Synaptic activity triggers nuclear export of SMRT reliant on multiple regions of the protein. Concommitantly, synaptic activity post-translationally enhances the transactivating potential of PGC-1α in a p38-dependent manner, as well as upregulating cyclic-AMP response element binding protein-dependent PGC-1α transcription. Activity-dependent targeting of PGC-1α results in enhanced gene expression mediated by the thyroid hormone receptor, a prototypical transcription factor coactivated by PGC-1α and repressed by SMRT. As a consequence of these events, SMRT is unable to antagonize PGC-1α-mediated resistance to oxidative stress in synaptically active neurons. Thus, PGC-1α and SMRT are antagonistic regulators of neuronal vulnerability to oxidative stress. Further, this coactivatorcorepressor antagonism is regulated by the activity status of the cell, with implications for neuronal viability.

In vitro study of antioxidant and scavenger properties of phenolic compounds from Lychnophora species

This paper describes the antioxidant effects of thirteen phenolic compounds isolated from plants of the genus Lychnophora. Two assays were performed to evaluate these effects: a cellular test that measured the luminol-enhanced chemiluminescence produced by neutrophils stimulated with opsonized zymosan and a cell-free test involving horseradish peroxidase-H2O2-luminol. In both assays, the antioxidant activity of the phenolic compounds was dependent on their concentration and chemical structure. Our results suggest that the ability of phenolic compounds from Lychnophora species to scavenge and inhibit the generation of ROS may be a mechanism underlying the anti-inflammatory activity of extracts from Lychnophora spp.

Flavonoids, total phenolics and antioxidant capacity: comparison between commercial green tea preparations

The potential health benefits attributed to green tea and its catechins such as antioxidant effects, cancer chemoprevention, and weight loss have led to a huge increase of green tea products in the food market. The objectives of this work were to analyze and compare these products in terms of phenolic contents and in vitro antioxidant capacity including tea bags, dehydrated leaves, and ready-to-drink preparations after standardization of the infusion preparation procedure. Total phenolics content in 1 cup of the different teas varied from 90 to 341 mg of catechin equivalents, and the highest and the lowest values were both those of the ready-to-drink products. Infusions prepared from tea bags had contents varying from 96 to 201 mg.200 mL-1, and there were no significant differences among batches. The DPPH radical scavenging and the Oxygen Radical Absorbing Capacities (ORAC) varied largely among the different tea preparations, from 23 to 131 mmoles of Trolox Equivalents (TE).200 mL-1 (DPPH), and from 1.2 to 5.1 mmoles of TE.200 mL-1 (ORAC), but again there were no differences among infusions or ready-to-drink commercial preparations. However, the antioxidant capacity of ready-to-drink products was partially due to the presence of other non-phenolic compounds such as ascorbic acid