Serum Nitric Oxide Levels Research Articles

Pigment epithelium-derived factor (PEDF) ameliorates arsenic-induced vascular endothelial dysfunction in rats and toxicity in endothelial EA.hy926 cells

Although the harmful effects of arsenic exposure on the cardiovascular system have received great attention, there is still no effective treatment. Vascular endothelial dysfunction (VED) is the initial step of cardiovascular diseases, where pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function. Here, we explored the protective role of PEDF in VED induced by arsenic, and its underlying molecular mechanism, designing an in vivo rat model of arsenic exposure recovery and in vitro endothelial EA. hy926 cell-based assays. The edema of aortic endothelial cells in rats significantly improved during recovery from arsenite exposure compared with rats exposed to 10 and 50 mg/L arsenite continuously. In addition, serum levels of nitric oxide (NO), von Willebrand factor, and nitric oxide synthase (inducible and total activities) in rats, which were greatly affected by arsenite exposure, returned to levels similar to those in the control group after recovery with distilled water. The recovery from arsenite exposure was associated with increased levels of PEDF; decreased protein levels of Fas, FasL, P53, and phospho-p38; and inhibited apoptosis in aortic endothelial cells in vivo. Recombinant human PEDF treatment (100 nM) prevented the toxic effects of arsenite (50 μM) on endothelial cells in vitro by increasing NO content, decreasing reactive oxygen species (ROS) levels, and inhibiting apoptosis, as well as increasing cell viability and decreasing levels of P53 and phospho-p38. Our findings suggest that PEDF protects endothelial cells from arsenic-induced VED by increasing NO release and inhibiting apoptosis, where P53 and p38MAPK are its main targets.

Beneficial effects of (-)-epigallocatechin-3-O-gallate on diabetic peripheral neuropathy in the rat model.

Diabetic neuropathic pain is characterized by spontaneous pain with hyperalgesia and allodynia. We investigated whether (-)-epigallocatechin-3-O-gallate could improve diabetic neuropathic pain development through hypoglycemic, hypolipidemic, antioxidant, and anti-inflammatory effects. Diabetes was induced in rats by streptozotocin (55 mg/kg/once) and treated with (-)-epigallocatechin-3-O-gallate (25 mg/kg/orally/once/daily/5 weeks). Diabetic rats showed an increase in serum levels of glucose, nitric oxide, triglyceride, total cholesterol, and low-density lipoprotein-cholesterol with a decrease in high-density lipoprotein-cholesterol and body weight. Also, there was an elevation in brain malondialdehyde with a marked reduction in brain levels of glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase. Furthermore, diabetic rats showed a clear reduction in plasma levels of insulin and an increase in plasma cytokines (interleukin-6 and tumor necrosis factor-α). Moreover, diabetic rats exhibited hyperalgesia as indicated by a hot plate, tail immersion, formalin, and carrageenan-induced edema tests as well as brain histopathological changes (neuron degeneration, gliosis, astrocytosis, congestion and hemorrhage). (-)-Epigallocatechin-3-O-gallate treatment ameliorated alterations in body weight, biochemical parameters, pain sensation, and histopathological changes in brain tissue. (-)-Epigallocatechin-3-O-gallate offers promising hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory effects, which can prevent the development and progression of diabetic neuropathic pain.

Protective Effect of Ocotillol, the Derivate of Ocotillol-Type Saponins in Panax Genus, against Acetic Acid-Induced Gastric Ulcer in Rats Based on Untargeted Metabolomics.

Gastric ulcer (GU), a prevalent digestive disease, has a high incidence and is seriously harmful to human health. Finding a natural drug with a gastroprotective effect is needed. Ocotillol, the derivate of ocotillol-type saponins in the Panax genus, possesses good anti-inflammatory activity. The study aimed to investigate the gastroprotective effect of ocotillol on acetic acid-induced GU rats. The serum levels of endothelin-1 (ET-1) and nitric oxide (NO), the gastric mucosa levels of epidermal growth factor, superoxide dismutase and NO were assessed. Hematoxylin and eosin staining of gastric mucosa for pathological changes and immunohistochemical staining of ET-1, epidermal growth factor receptors and inducible nitric oxide synthase were evaluated. A UPLC-QTOF-MS-based serum metabolomics approach was applied to explore the latent mechanism. A total of 21 potential metabolites involved in 7 metabolic pathways were identified. The study helps us to understand the pathogenesis of GU and to provide a potential natural anti-ulcer agent.

Serum adropin level is associated with endothelial dysfunction in patients with obstructive sleep apnea and hypopnea syndrome.

Adropin is a recently discovered peptide hormone that plays a vital role in metabolism and cardiovascular-cerebrovascular function. The purpose of this study is to investigate the role of circulating adropin levels in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) and further determine the relationship between serum adropin concentration and endothelial dysfunction in patients with OSAHS. Forty polysomnography-diagnosed patients with OSAHS and 21 age and sex-matched healthy controls were enrolled in the current study. Serum adropin level, endothelial function parameters including flow-mediated dilatation (FMD) of brachial artery, endothelin-1 (ET-1), and nitric oxide (NO) were measured in all participants. Serum adropin levels were significantly lower in patients with OSAHS compared to the control subjects. FMD was lower and serum ET-1 levels were higher in patients with OSAHS compared to control subjects. No significant difference was seen in serum NO levels between the two groups. Multivariate linear regression analysis revealed that serum adropin level was positively associated with FMD and negatively correlated with AHI. Additionally, serum adropin levels were lower in patients with OSAHS who had endothelial dysfunction compared with those patients without endothelial dysfunction. The receiver operating characteristic (ROC) analysis showed that area under the curve (AUC) for serum adropin in predicting endothelial dysfunction status in patients with OSAHS was 0.815 (95% CI 0.680-0.951, p = 0.001). The cutoff value of serum adropin level was less than 235.0 pg/mL, which provided the sensitivity and specificity of 81% and 75%, respectively, for the detection of endothelial dysfunction in patients with OSAHS. Lower circulating adropin levels are closely associated with endothelial dysfunction in patients with OSAHS. Circulating adropin level may serve as an early biomarker to predict the development of endothelial dysfunction before the emergence of clinical symptoms in patients with OSAHS.

Effect of video-assisted thoracoscopic surgery on pain stress indicators NO, IL-1β and IL-6 in the treatment of mediastinal tumor in children.

This study aimed to investigate the effect of video-assisted thoracoscopic surgery (VATS) on pain stress indicators nitric oxide (NO), interleukin-1β (IL-1β) and IL-6 in the treatment of mediastinal tumor in children, so as to explore the clinical application value of this surgery. A retrospective analysis was performed on 82 children with mediastinal tumor undergoing operation in Children's Hospital Affiliated to Zhengzhou University from January 2012 to January 2016. Among them, 48 children undergoing VATS were enrolled as an observation group, and 34 children undergoing conventional thoracotomy were enrolled as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the preoperative and postoperative expression levels of NO, IL-1β and IL-6. The intraoperative clinical data, postoperative pain degree and infection rate were observed and recorded in real time, and then compared between the two groups. Before operation (T0), there were no statistically significant differences between the two groups in serum NO, IL-1β and IL-6 expression levels, which were lower in the observation group than those in the control group at 12 h (T1) and 24 h (T2) after operation (P<0.05). The visual analog scale (VAS) score in the observation group was lower than that in the control group at T1 (P<0.05). Compared with the control group, the largest blade opening, intraoperative blood loss, drainage duration and postoperative pain degree were significantly improved in the observation group. The postoperative infection rate was 4.17% in the observation group, significantly lower than 17.64% in the control group. VATS is effective for postoperative pain stress indicators and infection control in children with mediastinal tumor, which is therefore more suitable for children with the disease and has a higher clinical value.

Influence of Oxidative stress and NF‐κβ/CRP/Bcl‐2 Signaling on Gentamicin Induced Renal Toxicology and the ameliorative effect of chloroform extract of Abrus precatorius in male Wistar rats

The kidneys play an important role in attenuating the toxicity of various drugs and chemicals. Gentamicin, a widely used effective aminoglycoside is one of such drugs, however, dose and time‐dependent nephrotoxicity limits its clinical use. This study evaluates the influence of oxidative stress, and inflammatory transcription factors in the pathogenesis of Gentamicin induced‐renal damage and the ameliorative potential of chloroform stem extract of Abrus precatorius. Twenty‐four male Wistar rats were divided into five equal groups. Group I was the negative control group while II was the positive control group which received gentamicin 100 mg/kg intra‐peritoneally daily for 6 days. Groups III and IV were pretreated with 100 and 200 mg/kg extract, respectively, for the first 3 days and then concurrently with gentamicin 100 mg/kg for 6 days. Blood samples, kidneys and kidney homogenates were collected for haematological, biochemical, histopathological and immunohistochemical analyses. Results revealed no significant hematological changes across the groups, Gentamicin caused significant increases in serum creatinine, urea, xanthine oxidase, nitric oxide, and myeloperoxidase levels. Gentamicin toxicity also resulted in increases in levels of renal advanced oxidative protein products, protein carbonyl, hydrogen peroxide, malondialdehyde levels. Furthermore, depletion in the activity of superoxide dismutase, glutathione S‐transferase, and contents of reduced glutathione, protein thiol, and non‐protein thiol. Gentamicin also caused focal areas of inflammation, fatty degeneration, congestion of vessels, tubular necrosis and glomerular atrophy in the kidney tissue. Levels of expressions of inflammatory mediators such as CRP and NF‐κβ levels were increased, alongside a decrease in Bcl‐2, an anti‐apoptotic protein. Gentamicin induces renal damage through the generation of oxidative stress, up‐regulation of pro‐inflammatory cytokines and down regulation of anti‐apoptotic protein. These were ameliorated with chloroform stem extract of Abrus precatorius.

Helicobacter pylori as an Initiating Factor of Complications in Patients With Cirrhosis: A Single-Center Observational Study.

Background and Aim: The relationship between liver cirrhosis and Helicobacter pylori (H. pylori) is a debatable matter. The aim of this study is to evaluate the possible association between H. pylori infection and liver cirrhosis.Methods: A single-center prospective cohort pilot study of 558 patients with cirrhosis was followed up for 1 year. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), vascular endothelial growth factor (VEGF) levels and Fecal H. pylori antigen were evaluated by enzyme-linked immunosorbent assay (ELISA). All patients with positive H. pylori were treated and then followed up for 3 months. Participants with eradicated H. pylori were followed up for one further year.Results: H. pylori-positive patients (48.4%) were associated with increased levels of serum CRP, TNF-α, IL-6, NO, and VEGF, as well as increased incidence of varices, portal hypertensive gastropathy, gastric antral vascular ectasia, hepatocellular carcinoma (HCC), spontaneous bacterial peritonitis, hepatic encephalopathy, portal vein thrombosis (PVT), and hepatorenal syndrome (all P < 0.05). Multivariate analysis models revealed that the presence of H. pylori was an independent risk variable for the development of portal vein thrombosis and hepatocellular carcinoma (P = 0.043, P = 0.037) respectively. After treatment of H. pylori infection, there was a significant reduction in all measured biochemical parameters and reported cirrhotic complications (all P < 0.05).Conclusion: Incidence of PVT and HCC development increased with H. pylori infection through increased inflammatory markers and vascular mediators. Moreover, its eradication may reduce the incidence of these complications.

Protective Effect of Genistein on the Morphine-Induced Kidney Disorders in Male Mice

Background: Morphine is a member of the naturally occurring phenanthrene alkaloids of opium. Genistein is a phytoestrogen, present in soy products. This study was designed to evaluate protective effects of genistein against morphine induced damages to the kidneys of mice. Methods: In this study, 48 male mice were randomly assigned to 8 groups: control (saline), morphine treated group (10 mg/kg/day); genistein groups (1, 2, 4 mg/kg/day) and morphine plus genistein treated group. Drugs were administrated intraperitoneally for 30 consequent days. Weight of animals and kidneys, glomeruli characteristics, kidney function markers and blood serum nitric oxide level has been studied. Result: The results indicated that morphine administration significantly increased Lactate dehydrogenase (LDH), Blood urea nitrogen (BUN), creatinine and nitric oxide levels compared to the control ( saline) group (P<0.05). Genistein in all doses and genistein plus morphine at the dose of 4 mg/kg significantly decreased LDH, BUN, creatinine, glomerular diameter and nitric oxide levels compared to the control and morphine groups (p<0.05). Conclusion: It seems that genistein administration improved kidney damages induced by morphine in mice.

Evodiamine via targeting nNOS and AMPA receptor GluA1 inhibits nitroglycerin-induced migraine-like response

Ethnopharmacological relevanceEvodiamine (EVO) is a natural compound derived from Tetradium ruticarpum (A.Juss.) T.G.Hartley used to treat pain and migraine in traditional Chinese medicine. EVO is the primary active ingredient of Tetradium ruticarpum. However, the preventive effect of EVO against migraine remains unexplored. Aim of the studyTo investigate the preventive effect of EVO against nitroglycerin (NTG)-induced acute migraine in rats. Materials and methodsMale Sprague-Dawley rats were intragastrically administered EVO (45 or 90 mg/kg) for nine days. To establish an acute migraine model, we subcutaneously injected rats with a 10 mg/kg NTG solution. The migraine-like behavior of the rats was evaluated via the formalin test and the warm water tail-withdrawal assay. The periaqueductal gray (PAG) and serum samples were collected from the rats and used to determine the effect of EVO on the levels of serum nitric oxide (NO), CGRP, c-Fos, neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and the α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor GluA1. ResultsThe formalin test and the warm water tail-withdrawal assay showed that EVO inhibited the licking foot/shaking response and reversed the shortened tail-withdrawal latency in NTG-treated rats. Additionally, EVO suppressed serum NO levels and reduced the mRNA/protein expression of c-Fos and nNOS, but not iNOS, in the PAG. Furthermore, EVO suppressed total protein expression of the AMPA receptor GluA1 and its phosphorylation at Ser831 and Ser845. ConclusionsThis study showed that EVO inhibits the migraine-like pain response and that this beneficial effect might be attributed to the regulation of nNOS and suppression of the AMPA receptor GluA1. We suggest that EVO has the potential to treat migraine as a lead compound of natural origin.

Melatonin and oxidative stress in melasma - an unexplored territory; a prospective study.

Melasma, an acquired disorder of hyperpigmentation, is the most common pigmentary disorder in India. Many factors are implicated in the pathogenesis, and recently the role of oxidative damage including melatonin has been postulated. This study was undertaken to evaluate the role of oxidative stress and serum melatonin in pathogenesis of melasma. Seventy-five patients with melasma and an equal number of age and sex-matched controls were included in the study. Clinical characteristics were noted, and baseline severity assessment using modified Melasma Area and Severity Index (MASI) was done in all patients. Serum melatonin, catalase, protein carbonyl, and nitric oxide levels were measured and compared between cases and controls. The serum levels of melatonin and catalase were significantly lower among the cases as compared to controls, while the serum levels of protein carbonyl and nitric oxide were significantly higher in cases compared to controls. There was no statistically significant correlation between these markers of oxidative stress and severity of the disease. Oxidative stress is increased in patients with melasma compared to the control group in this study. A state of melatonin deficit also exists in patients with melasma. No correlation between the oxidative stress and severity of the disease was found. Further and larger studies including therapeutic trials with powerful antioxidants are warranted.

Serum and Salivary Level of Nitric Oxide (NOx) and CRP in Oral Lichen Planus (OLP) Patients.

Statement of the Problem: Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease with unclear etiology while a few cases of disease become malignant.Purpose: This study aimed to evaluate the level of nitric oxide (NOx) and C-reactive protein (CRP) as oxidative stress and inflammation status in sample of OLP patients.Materials and Method: In this case-control study, serum and salivary NOx and CRP levels were evaluated in twenty two OLP patients as the case group confirmed by clinical and histopathological diagnosis, and twenty two healthy control groups collected from Tooba Oral Pathology Laboratory in Sari in 2016. The data were analyzed by using independent-samples t-test, Mann-Whitney U-test and Chi-square by using SPSS version 21. The statistical significant level was considered at p< 0.05.Results: Salivary and serum NOx levels in case group showed statistically significantly higher than healthy control group (p= 0.035 and p= 0.001, respectively). CRP values were significantly higher both in serum (p= 0.001) and in saliva (p= 0.035). A significant correlation was found between CRP and NOx values in serum (r= 0.521, p= 0.0001) and saliva (r= 0.427, p= 0.045).Conclusion: Oxidative stress causes damage to organs in the human body. Correct understanding of oxidative stress and its association with free radicals and inflammatory markers related to oral disease are important for effective treatments. The results of the study advocate the effects of NOx and CRP levels in pathogenesis of OLP. Therefore, antioxidant drugs might probably be considered in the treatment of OLP.

Effect of different high altitudes on vascular endothelial function in healthy people.

Background:The aim of the study was to provide a theoretical basis for the early diagnosis and prediction of acute altitude sickness, to provide a better entry mode for healthy people from plain areas to plateau areas, and to preliminarily clarify the possible mechanism of this approach.Methods:We measured endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), nitric oxide (NO), and hypoxia-inducible factor 1 (HIF-1) levels in each sample and determined flow-mediated dilation (FMD) values using a portable OMRON color Doppler with a 7.0- to 12.0-MHz linear array probe. We used the Lewis Lake score to diagnose acute mountain sickness (AMS) and to stratify the disease severity.Results:We found no cases of AMS at any of the studied elevation gradients. We found significant differences in FMD values between individuals when at 400 m above sea level and when at 2200, 3200, and 4200 m above sea level (P < .05) but found no significant differences among those at 2200, 3200, and 4200 m. Our variance analysis showed that serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in individuals at ≥3000 m and those at subplateau and plain areas (<3000 m) significantly differed (P < .05). The level of these factors also significantly differed between individuals at elevation gradients of plateau areas (3260 m vs 4270 m) (P < .05). We found no significant differences in serum ET-1, VEGF, and ADMA levels between individuals at the plateau (2260 m) and plain (400 m) areas (P > .05). NO and HIF-1 levels were significantly different in serum samples from individuals between the plateau (2260 m) and plain (400 m) areas (P < .05). However, with increasing altitude, the NO level gradually increased, whereas ET-1, ADMA, VEGF, and HIF-1 levels showed a decreasing trend. With the increase of altitude, there is no correlation between the trend of FMD and hematologic-related factors such as VEGF, NO, and HIF-1.Conclusion:A healthy young male population ascending to a high-altitude area experiences a low incidence of AMS. Entering an acute plateau exposure environment from different altitude gradients may weaken the effect of acute highland exposure on vascular endothelial dysfunction in healthy individuals. Changes in serum ET-1, VEGF, ADMA, NO, and HIF-1 levels in healthy young men may be related to the body's self-regulation and protect healthy individuals from AMS. A short stay in a subplateau region may initiate an oxygen-free preconditioning process in healthy individuals, thereby protecting them from AMS. Noninvasive brachial artery endothelial function test instead of the detection of invasive hematologic-related factors for early diagnosis and prediction of the occurrence and severity of acute high-altitude disease is still lack of sufficient theoretical basis.

RETRACTED: The antidepressant effects of L-arginine on chronic mild stress-induced depression by augmenting the expression of brain-derived neurotrophic factor in rats

In the present study, the antidepressant effects of l-arginine in a rat model of chronic mild stress-induced depression were investigated. Animals were divided into group I (sham), group II (control, depression), group III (10 mg/kg l-arginine), group IV (20 mg/kg l-arginine), and group V (10 mg/kg venlafaxine, positive control). The doses were orally administered for 30 consecutive days. Sucrose preference analysis as well as forced swim and open field tests were performed. Serum cortisol, nitric oxide (NO), and monoamine levels in brain tissue were then measured. Brain-derived neurotrophic factor (BDNF) expression was also examined. Supplementation with l-arginine significantly increased the sucrose preference ratio, locomotor activity, and monoamines and decreased serum cortisol and NO levels. The mRNA and protein expression of BDNF in the brain tissue was significantly reduced (>50 %) in control rats. However, supplementation with l-arginine significantly increased BDNF mRNA expression (>50 %) in both groups. Similarly, increased BDNF protein expression after l-arginine treatment was confirmed using Western blot and immunohistochemical analyses. In conclusion, l-arginine supplementation may be effective against chronic stress-induced depression.

Serum levels of nitric oxide and endothelin-1 in vasculopathy managed with hyperbaric oxygen therapy.

Roles of nitric oxide (NO) and endothelin-1 (ET-1) in the local regulation of blood flow under physiological conditions are important and well known, while data on their effects and interactions in conditions of hyperbaric hyperoxia is still insufficient. This was a prospective observational study which included patients who underwent hyperbaric oxygen therapy (HBOT) in accordance with existing therapeutic protocol for peripherial arterial disease (PAD) during time period of six months, between january and july of 2016. Clinical stage of PAD according to Fontain was taken into account, as well as risk factors, demographic, anthropometric and clinical characteristics of studied patients. The study included 64 patients with a mean age (±Sd) 60.2±12.7 years, of whom 28 were female. Patients' NO serum levels in all observed categories before and after HBOT were not signifficantly different, except for stage II PAD (NObefore HBOT 21.9±9.6 vs. NOafter HBOT 26.2±12.1 (p = 0.04)). On the contrary, in all studied patients ET-1 level increased signifficantly after HBOT (ET-1before HBOT 4.2±11.6 vs. ET-1after 18.3±21.0 (p < 0.001)). Treatment of PAD using HBOT leads to the predominance of vasoconstrictor effects probably caused by elevation of serum ET-1 concentrations, while other factors such as exposure time to hyperbaric conditions, activation of antioxidant molecules, and the influx of other interfering substances must be considered in interpreting the effects of NO molecules.

A comparative study of novel biomarkers on preeclampsia in relation to body mass index

Objective of the study was to compare serum level of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), asymmetric dimethylarginine (ADMA), arginine, placental growth factor (PIGF), soluble Fms like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase, in normotensive and preeclamptic pregnancies in relation to body mass index (BMI). The study was done on 100 healthy normotensive and 100 preeclamptic pregnant women. Based on BMI, they were categorized into three groups. Group 1 (&lt;25 kg/m2), group 2 (25 – 30 kg/m2) and group 3 (&gt;30 kg/m2). ADMA, eNOS, arginine, PlGF, sFlt-1, sEng were estimated by ELISA method, and MDA, NO, GPx, SOD, and catalase by spectrophotometric method. Statistically, a significant difference was not observed within normotensive and preeclampsia in relation to BMI. But when respective normotensive was compared with preeclampsia, there was a high increase of ADMA, sFlt-1, sEng, and MDA. A significant decrease was observed in arginine, eNOS, NO, GPx, SOD, and catalase in preeclampsia. This study shows that though preeclampsia is associated with overweight and obesity, but during pregnancy, higher BMI has no additional deleterious effect in preeclampsia.

Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l-NAME-induced hypertension.

This study was designed to evaluate the protective effects of hydrogen sulphide (H2 S) against NG-Nitro l-Arginine Methyl Ester (l-NAME)-induced hypertension and its possible effects on the inflammatory process, oxidative stress, and vascular remodelling in rats. Forty male Wistar Albino rats were assigned to four equal groups: the control group, the H2 S control group, the hypertensive group, and the treated group, which received concomitant treatment with sodium hydrosulphide (NaHS) and l-NAME. Systolic blood pressure (SBP) was measured weekly. Serum levels of nitric oxide (NO), total peroxide, and total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Aortic weight and length were measured and the aortic weight/length ratio determined. Aortic fold expression of interferon-γ (IFN-γ) and vascular cell adhesion molecule-1 (VCAM-1) mRNA was measured using qPCR. Aortic media thickness and elastin content were measured morphometrically. l-NAME administration increased SBP, serum levels of total peroxide and OSI, but reduced serum levels of NO and TAC. Aortic fold expression of IFN-γ and VCAM-1 mRNA, aortic weight, aortic weight/length ratio, aortic media thickness, and elastin area percentage were increased in the hypertensive group. Concurrent administration of l-NAME and H2 S attenuated these changes. Thus, H2 S could attenuate the increase in ABP through restoration of the NO level, reduction in the oxidative state, and attenuation of the inflammatory process, thereby reduced vascular remodelling.

Resveratrol Supplementation Prevents Hypertension in Hypertensive Pregnant Rats by Increasing Sodium Excretion and Serum Nitric Oxide Level.

Background Pregnancy-induced hypertension (PIH) remains a major cause of morbidity and mortality in pregnancy worldwide. This study was designed to study the blood pressure-lowering effect of resveratrol (RES) in a salt-induced hypertensive pregnant rat model. Methods Forty female Sprague Dawley (SD) rats were randomized into 4 groups: Normal Preg (0.9% salt diet), Normal Preg + RES (0.9% salt diet plus daily oral RES for 4 weeks), Salt Preg (8% salt diet), and Salt Preg + RES (8% salt diet plus daily oral RES for 4 weeks). Noninvasive blood pressure was recorded on gestational days 7 and 14. On the gestational day 19, foetuses were weighed, and blood and urine samples were harvested for electrolytes and biochemical assays. Results RES significantly reduced SBP, DBP, and MAP on gestational days 7 and 14 in the Salt Preg + RES group compared to the Salt Preg group (all P < 0.05). Compared to the Salt Preg group, the foetal weight, serum NO level, urinary sodium, and 24 hour urine volume were significantly increased in the Salt Preg + RES group (all P < 0.05). Compared to the Salt Preg group, the foetal weight, serum NO level, urinary sodium, and 24 hour urine volume were significantly increased in the Salt Preg + RES group (all P < 0.05). Compared to the Salt Preg group, the foetal weight, serum NO level, urinary sodium, and 24 hour urine volume were significantly increased in the Salt Preg + RES group (all Conclusions RES decreases blood pressure in a hypertensive pregnant rat model. Increasing sodium excretion and serum nitric oxide level might be, at least part of, the underlying mechanisms.

Evaluation of Antidepressant, Antianxiolytic, and Antioxidant Effects of Echium amoenum L. Extract on Social Isolation Stress of Male Mice

Background: One of the most important herbal remedies in Iran is Echium amoenum L. It has been used in traditional Iranian pharmaceutical formulations and has provided an interesting area of research for various drug activities. Objectives: The present study aimed to investigate the antidepressant and antianxiolytic effects of hydroalcoholic extract of Echium amoenum L. in a socially isolated model of male mice. Methods: In this experimental study, 50 male Balb/c mice weighing 25 to 30 g were divided into five groups of 10 mice. The control group received normal saline. The treatment groups received the Echium amoenum L. hydroalcoholic extract for five days at doses of 50, 75, and 100 mg/kg via i.p injection and the negative control group received social isolation and normal saline. Results: Echium amoenum L. hydroalcoholic extract at doses of 50, 75, and 100 mg/kg significantly reduced immobility in the forced swimming test in mice exposed to social isolation stress. Echium amoenum L. extract at doses of 75 and 100 mg/kg significantly increased the number of crossings in the center of the open-field box. The time of staying in the open arms increased significantly in groups receiving the extract at 50, 75, and 100 mg/kg. Treatment with Echium amoenum L. extract reduced the serum and brain tissue levels of nitric oxide and malondialdehyde in mice exposed to social isolation stress and enhanced the total antioxidant capacity of serum and brain tissue. Conclusions: Modulating the nitric oxide system and reducing oxidative stress may be essential mechanisms of Echium amoenum L. extract in reducing depression and anxiety in mice.

Antarctic Krill Oil Attenuates Oxidative Stress via the KEAP1-NRF2 Signaling in Patients with Coronary Heart Disease.

Background Antarctic krill oil (AKO) has strong antioxidant activities and is effective for alleviating coronary heart disease (CHD). Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) axis is a crucial antioxidant signaling pathway. Thus, AKO may exert its antioxidant effects on CHD patients via KEAP1-NRF2 signaling. Methods AKO fatty acid (FA) profiles were analyzed by using gas chromatography (GC). One hundred CHD patients were divided into the intervention (IG, AKO) and control (CG, placebo) groups. Before and after 1, 2, and 3 months of intervention, we measured serum levels of reactive oxygen species (ROS), 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione peroxidase (GPx), and KEAP1 and NRF2 levels in peripheral blood leukocytes (PBLs). Serum FAs were measured by GC at baseline and after 3-month intervention. Results AKO contains rich eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which is more than 27% of total FA. The levels of EPA and DHA, KEAP1, and NRF2 in the IG group were higher than those in the CG group (p < 0.05). Serum levels of ROS, 8-OHdG, NO, and MDA in the IG group were lower than those in the CG group, whereas the levels of SOD, GSH, and GPx in the IG group were higher than those in the CG group (p < 0.05). Serum levels of saturated fatty acids (UFA) in the IG group were higher than those in the CG group, whereas reverse results were obtained for the levels of saturated fatty acids (SFA). Serum levels of EPA and DHA had a strong negative relationship with the level of ROS, whereas the ROS level had a strong negative relationship with the levels of KEAP1-NRF2. Conclusion AKO increases antioxidant capacities of CHD patients via the KEAP1-NRF2 signaling in the PBL.

Association between expression of AMPK pathway and adiponectin, leptin, and vascular endothelial function in rats with coronary heart disease.

The aim of this study was to explore the association between the expression of adenosine monophosphate-activated protein kinase (AMPK) pathway and adiponectin (APN), leptin, and vascular endothelial function in rats with coronary heart disease (CHD). Experimental rats were divided into three groups, including: control (Col) group, CHD model (CHD) group, and CHD+AMPK activator (CHD+AICAR) group. Except those in Col group, all rats were fed with high-fat diet and intraperitoneally injected with pituitrin to establish the CHD model. The levels of serum APN, leptin, and endothelin-1 (ET-1) were determined via enzyme-linked immunosorbent assay (ELISA). The content of serum nitric oxide (NO) was detected using the nitrate reductase method. Meanwhile, the expression of AMPK pathway-related protein AMPKα in vascular endothelial tissues was detected via Western blotting (WB). Aortic vascular endothelial cells (VECs) were cultured with AICAR or ET-1 in vitro. Subsequently, the expressions of AMPK pathway and protein kinase B (AKT) pathway-related proteins were determined through co-immunoprecipitation and WB. Moreover, the expression level of NO in VECs was determined using the DAF-FM DA fluorescence probe. Compared with Col group, CHD group showed significantly decreased levels of serum APN and NO (p<0.05), significantly increased the levels of leptin and ET-1 (p<0.05), as well as remarkably decreased protein expression of p-AMPKα in vascular endothelial tissues (p<0.05). After injection of AMPK activator AICAR (200 mg/kg), the protein expression of p-AMPKα in CHD rats was significantly activated (p<0.05). The levels of serum APN and NO were remarkably upregulated (p<0.05), while the levels of leptin and ET-1 were significantly reduced (p<0.05). Besides, AICAR could evidently activate the activity of AMPK pathway in VECs in vitro, upregulate the protein levels of p-eNOS (Ser1177) and p-AMPKα, and promote the secretion of NO (p<0.05). In addition, AICAR remarkably inhibited ET-1-induced expression of AKT pathway (p<0.05). Activating the AMPK pathway may play a positive role in the normal function of VECs and exert a certain curative effect on CHD in rats.