Serum Nitric Oxide Levels Research Articles

The Effect of Simvastatin on Nitric Oxide and hs-CRP Levels in patients with Liver Cirrhosis at Dr. Moewardi Hospital, Surakarta

Background: The prevalence of liver cirrhosis (SH) worldwide is at seventh place as the cause of death. Increased pressure in the portal vein Portal Hypertension (HP) causes esopha­geal varices and the more likely the patient to bleed. Endothelial dysfunction in cirrhosis of the liver causes a decrease in nitric oxide (NO) levels resulting in an imbalance between relaxation factors and portal vein contractions and increasing hs-CRP levels. Simvastatin can increase NO levels and improve endothelial dysfunction in patients with SH and can reduce levels of hs-CRP. This study aimed to determine the effect of simvastatin administration on nitric oxide and hs-CRP level in patients with liver cirrhosis. Subjects and Method: This was a randomized controlled trial conducted at Dr. Moewardi hospital, Surakarta, Central Java. A sample of 29 patients was divided into treatment and control groups. 14 patients in the treatment group were given simvastatin dose of 20 mg. 15 patients in the control group received a placebo. The dependent variable was a nitric oxide and hs-CRP levels. The inde­pendent variable was Simvastatin administration. Nitric oxide serum level was measured by an enzyme-linked immunosorbent assay (ELISA). Hs-CRP level was measured by the immune­chemilu­minescent method. The data were analyzed by t-test. Results: NO level after Simvastatin 20 mg administration (Mean= 7.93 µg/mL; SD= 1.78 µg/ mL) was higher than before (Mean= 5.14 µg/mL; SD= 2.25 µg/mL) and it was statistically significant (p = 0.001). Hs-CRP level after Simvastatin 20 mg administration (Mean= 2.04 mg/L; SD= 0.80 mg/L) was lowered than before (Mean= 7.82 mg/L; SD= 1.15 mg/L) and it was statistically significant (p= 0.001). Conclusion: Simvastatin administration increases NO serum levels and reduces the hs-CRP level in patients with liver cirrhosis. Keywords : nitric oxide, hs-CRP, simvastatin, liver cirrhosis Correspondence: Budhi Hariyanto. Masters Program in Family Medicine, Universitas Sebelas Maret. Jl. Ir Sutami 36A, Surakarta 57126, Centra Java. Email: antohariyanto787@gmail.com. Mobile: 0823280­10442. Indonesian Journal of Medicine (2019), 4(1): 9-14 https://doi.org/10.26911/theijmed.2019.04.01.02

The role of total flavone of Camellia on cerebrovascular vasopasm after subarachnoid hemorrhage in rats

Background: This study was undertaken to explore the role of total flavones of Camellia (TFC) on the cerebrovascular dysfunction in rats after experimental subarachnoid hemorrhage (SAH). Materials and Methods: The contraction and dilation of cerebral basilar artery (BA), nitric oxide (NO) level, and nitric oxide synthase (NOS) activity in rat serum and the expression of endothelial NOS (eNOS) in cerebral vessels were measured. Furthermore, the effect of potassium channel blockers, endothelium removal, L-NG-nitroarginine methyl ester (L-NAME), or prostacyclin I2 (PG I2) production inhibitor on the response of isolated BA derived from normal rats was also evaluated to explore the underlying mechanism of vasodilation induced by total flavones. Results: The contraction of rat BA to U46619 markedly increased and the vasodilation to acetylcholine remarkably reduced after SAH. Interestingly, these vascular dysfunctions were profoundly ameliorated by pretreatment of TFC. Moreover, total flavones could induce a concentration-dependent relaxation in isolated BA from normal rats, which was obviously eliminated by co-application of potassium channel blockers, ChTx and Apamin, application of L-NAME, or endothelial removal. In addition, total flavones pretreatment obviously improved the expression of eNOS in BA, serum NO level, and NOS activity at 48 h after SAH. Conclusion: These findings revealed that TFC has protective effect on cerebrovascular dysfunction after SAH and demonstrated that the protection could be due to its upregulation of eNOS expression and activation of potassium channel.

Evaluation of the protective effects of Ganoderma atrum polysaccharide on acrylamide-induced injury in small intestine tissue of rats.

This research investigated the protective effects of Ganoderma atrum polysaccharide (PSG-1) on acrylamide (AA) induced intestinal injury in rats. Our results showed that PSG-1 pretreatment effectively reduced the levels of malondialdehyde (MDA), but increased the activity of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and the total glutathione (T-GSH), and significantly reduced oxidative stress in AA treated rats. Furthermore, PSG-1 pretreatment down-regulated pro-inflammatory cytokines i.e. interleukin 2 (IL-2), interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) and increased the amounts of anti-inflammatory cytokines i.e. interleukin 4 (IL-4) and interleukin 10 (IL-10), significantly reducing an inflammatory response in the intestines of rats. In AA induced intestinal injury, the tissue uric acid (UA) level and alkaline phosphatase (ALP) activity and the serum level of d-lactic acid (d-lactate), nitric oxide (NO) and endothelin-1 (ET-1) decreased significantly after treatment with PSG-1 and N-acetylcysteine (NAC). Histological observations of the small intestine confirmed the protective effects of different doses of PSG-1. These findings suggested that PSG-1 pretreatment could alleviate AA-induced oxidative stress, reduce inflammatory response, and inhibit AA absorption by protecting the intestinal barrier. Therefore, Ganoderma atrum polysaccharide has the potential to be a dietary supplement ingredient that provides protection against AA-induced gut injury.

Effects of supplementation of Bacillus spp. on blood metabolites, antioxidant status, and gene expression pattern of selective cytokines in growing Barki lambs.

Objective:In this study, we investigated the potential immune-enhancing effects in addition to anti-oxidative stress properties of commercially accessible Bacillus subtilis supplementation in Barki lambs.Materials and Methods:Twenty apparently healthy weaned Barki lambs were used in this study and distributed randomly into two experimental groups: Negative control group, received control basal diet without any feed supplements and a supplemented group, received control basal diet supplemented with water added to commercially accessible bacilli at 1 gm/l/day for 30 consecutive days. Blood samples were collected from each lamb before starting the experiment (T0), 2 weeks (T15), and 4 weeks (T30) post-supplementation for serum biochemical analyses, total leucocytes and lymphocytes count, and real-time polymerase chain reaction assays.Results:The supplemented group showed a significant increase (p < 0.05) in the total number of leukocytes and the number of lymphocytes, lysozyme activity, reduced glutathione, total antioxidant capacity with a significantly lower malondialdehyde values at T30 and significantly higher levels (p < 0.05) of serum catalase and nitric oxide at T15 as compared with control ones. B. subtilis elicited maximal up-regulation of most of the studied genes compared with the control group.Conclusion:The results herein suggest that B. subtilis could be used as useful nutritional supplements to support the immune system in healthy lambs.

Serum adropin as a predictive biomarker of erectile dysfunction in coronary artery disease patients.

IntroductionErectile dysfunction (ED) is associated with various comorbidities and an early diagnosis and treatment is necessary to avoid the development of these comorbidities. Unfortunately, there is no biochemical marker that can be used for early diagnosis of ED. Nitric oxide (NO) is released by nerve and endothelial cells in the corpora cavernosa of the penis and is believed to be the main vasoactive chemical mediator of penile erection. Adropin is a regulatory peptide which has effects on NO bioavailability and energy homeostasis. We hypothesized that adropin may contribute to the pathogenesis of ED because of the presence of both metabolic effects and the influence on NO bioavailability. To confirm this hypothesis, we investigated the relationship between ED and serum adropin and NO levels.Material and methodsSeventy-five ED patients were enrolled for this study and the patients were divided into two groups according to angiographic scoring. Serum NO and adropin levels were measured by the Griess reaction and ELISA method, respectively.ResultsSerum adropin and NO levels were found to be lower in the group which has higher angiographic score and the difference in NO was statistically significant. Also, adropin has a significant correlation between IIEF scores in ED patients.ConclusionsThis is the first study in the literature investigating the levels of adropin in ED patients having coronary artery disease. The adropin molecule shows a promising future in clarifying the etiopathogenesis of ED. More comprehensive and multicenter studies are needed to reveal the role of adropin in ED and the effects of treatment on this molecule.

Protective effect of Traditional Chinese medicine Shuangwu Zhentong Capsule on collagen-induced arthritis in rats and possible mechanisms

The aim of this study was to investigate the protective effect of Traditional Chinese medicine Shuangwu Zhentong Capsule (SZC) on collagen-induced arthritis (CIA) and the possible mechanisms. Sixty rats were randomly divided into control and model: low-, medium-, and high-dose SZC and prednisone acetate (PA) groups, with 10 rats in each group. The CIA model was established in later 5 groups. The rats in low-, medium-, and high-dose SZC groups were intragastricallly administered with SZC, with dose of 0.5, 1, and 2 g/kg, respectively. The PA group was intragastricallly administered with 5 mg/kg PA. The treatment was performed for 3 weeks. Before treatment and after treatment, the paw swelling degree and polyarthritis index score of rats were measured. At the end of experiment, the serum tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) levels were determined. The expressions of Ras and Raf-1 protein in synovial tissue were detected. Results showed that, after treatment, compared with model group, in high-dose SZC and PA groups, the paw swelling degree, polyarthritis index score, serum TNF-α, IL-1β and NO levels, and synovial tissue Ras and Raf-1 protein levels were significantly decreased, respectively ( P &lt; 0.05). In conclusion, SZC has obvious protective effects on CIA in rats. The mechanisms may be related to its resistance of inflammatory reaction and down-regulation of Ras and Raf-l protein expressions in synovial tissue.

Hepatoprotective activity of royal jelly on mercuric chloride–induced damage model in rats

Background: Mercuric chloride (MC) is the chemical composition of mercury and chlorine with many side effects such as oxidative stress referring to mercury toxicity. Royal jelly (RJ) as a honey bee secretion has antioxidant activities. This study was designed to evaluate the effects of RJ against the parameters of hepatic damage in male rats induced by MC toxicity. Materials and Methods: In this study, 48 male rats were randomly assigned into six groups: sham (saline) and MC control (50 mg/kg) groups; RJ groups (200 mg/kg RJ for 1 day and 200 mg/kg RJ for 7 days, orally) and MC + RJ groups (200 mg/kg RJ orally + 50 mg/kg MC intraperitoneally for 1 day, and 200 mg/kg RJ orally and 50 mg/kg MC intraperitoneally for 7 days). Griess technique was used for the determination of serum nitric oxide (NO) level. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) concentrations were determined for liver functional disturbances value. In addition, thiobarbituric acid reactive species, antioxidant capacity, the diameter of hepatocytes, and the central hepatic vein (CHV) were investigated. Results: MC administration significantly increased the liver malondialdehyde (MDA) and NO levels, the mean diameter of CHV and hepatocyte, hepatic enzymes, and decreased tissue Ferric reducing antioxidant power (FRAP) level compared to the sham group (P < 0.01). The RJ and RJ + MC in all treatments significantly reduced the mean diameter of hepatocyte and CHV, hepatic enzymes, renal MDA and NO levels, and increased tissue FRAP level compared to the MC control group (P < 0.01). It seems that RJ administration recovers the hepatic injury induced by MC in rats.

Assessment of Oxidative Status in Foot Diseases of Sheep

Background: Oxidative stress plays an important role in the etiology and/or progression of various diseases in the livestock. The aim of this study was to investigate the relationship between foot diseases and oxidant and antioxidant levels, determining catalase (CAT) and glutathione peroxidase (GSH-Px) activities and malondialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) concentrations in sheep with foot disease such as interdigital dermatitis, footrot and interdigital pouch infection (biflex canal inflammation).Materials, Methods &amp; Results: In the study, a total of 70 sheep aged between 1 and 3, 20 sheep with interdigital dermatitis, 20 with foot-rot, 10 with interdigital pouch inflammation and 20 clinically healthy Akkaraman sheep, were used. The blood samples collected from the V. Jugularis of the sheep were centrifuged and their serums were obtained. MDA and NO levels of the sheep with interdigital dermatitis, footrot and interdigital pouch infection were found to be significantly higher than those of animals in the control group (P &lt; 0.001). CAT activity was determined to be significantly lower in all diseased animals than in the animals in the control group (P &lt; 0.001). GSH-Px and GSH levels were significantly lower in the animals with interdigital dermatitis than in the control group (respectively P &lt; 0.001, P &lt; 0.05).Discussion: Oxidative stress regulates the metabolic activity of some organs and plays an important role in productivity in livestock. The oxidative stress is reported that caused by the increase in the production of excessive free radicals resulting from the exposure of animals to various stress factors and by the weakening of the antioxidant defense has an important role in the pathogenesis of numerous diseases such as foot diseases. In the presence of various stress factors, the level of malondialdehyde (MDA) and nitric oxide (NO) increases. MDA is determine the degree of cellular damage in tissues. Nitric oxide is produced in large quantities by macrophages in case of bacterial infections and exhibits antibacterial properties against pathogenic microorganisms. For this reason, NO is very high levels in inflammatory diseases. Catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) is some of the important antioxidants and play an important role in the oxidative defense of tissues. In this study, the increase in serum MDA and NO levels was mostly found in interdigital dermatitis cases, then in footrot cases and finally in interdigital pouch infection cases. Serum CAT levels were found to be significantly lower than that of the control group (P &lt; 0.001). In this study, the highest decrease in serum CAT levels was detected in interdigital dermatitis cases and followed by footrot cases and interdigital pouch infection cases, respectively. Serum GSH-Px and GSH levels were found to be significantly lower in interdigital dermatitis cases than those in the control group (respectively P &lt; 0.001, P &lt; 0.05). There was no statistically significant difference found between the serum GSH-Px and GSH levels of footrot and interdigital pouch infection cases, and the control group (P &gt; 0.05). We found that serum MDA and NO levels were found to significantly increase in sheep with foot disease and serum CAT levels were found to be significantly lower. The results of this research indicate that MDA, NO and CAT activities may be more reliable parameters than GSH-Px and GSH activities in order to determine oxidative stress in sheep with foot diseases. In conclusion, this study reveals that there is a relationship between foot diseases and oxidant/antioxidant balance in sheep and it shows that the oxidative stress and lipid peroxidation develop due to the increase of free radicals.

Thymoquinone Prevents Myocardial and Perivascular Fibrosis Induced by Chronic Lipopolysaccharide Exposure in Male Rats: - Thymoquinone and Cardiac Fibrosis.

ObjectivesThymoquinone (TQ) is one of the active ingredients of herbal plants such as Nigella sativa L. (NS) which has beneficial effects on the body. The beneficial effects of TQ on the cardiovascular system have reported. This study aimed to investigate the effect of TQ on cardiac fibrosis and permeability, serum and tissue concentration of inflammatory markers and oxidative stress status in chronic lipopolysaccharide exposure in male rats.MethodsSeventy male Wistar rats were randomly divided into five groups as follows: (1) control; (2) LPS (1 mg/kg/day); (3–5) LPS + TQ with three doses of 2, 5 and 10 mg/kg (n=14 in each group). After 3 weeks, serum and cardiac levels of IL-1β, TNF-α and nitric oxide (NO) metabolites, and cardiac levels of malondialdehyde (MDA), total thiol groups, catalase (CAT) and superoxide dismutase (SOD) activities, permeability of heart tissue (evaluated by Evans blue dye method) and myocardial fibrosis were determined, histologically.ResultsLPS administration induced myocardial and perivascular fibrosis and increased cardiac oxidative stress (MDA), inflammatory markers and heart permeability, while, reduced anti-oxidative enzymes (SOD and CAT) and the total thiol group. Administration of TQ significantly attenuated these observations.ConclusionTQ improved myocardial and perivascular fibrosis through suppression of chronic inflammation and improving oxidative stress status and can be considered for attenuation of cardiac fibrosis in conditions with chronic low-grade inflammation.

Factors Regulating Nitric Oxide Production in Piper Sarmentosum Aqueous Extract Treated Spontaneous Hypertensive Rats

Introduction: High blood pressure is a major risk factor for cardiovascular diseases which is one of the leading causes of death worldwide. Piper sarmentosum (PS) leaves have been widely used in traditional medicine and it has been proven for its antihypertensive and antioxidant effects. This study aims to evaluate the antihypertensive potential of PS aqueous extract (PSAE) and to investigate the factors modulating nitric oxide (NO) production through its anti-oxidant activities. Materials and Methods: PS leaves were extracted with distilled water and freezedried. The PSAE was examined to quantify their antioxidant activities through DPPH and FRAP test. It is also screened for total phenolic and flavonoids content. The antihypertensive effect of PSAE in SHR was evaluated using four different groups (n=6); C group (negative control), K group (PSAE 500mg/kg), P group (3 mg/kg perindopril) and M group (PSAE + 1.5 mg/kg perindopril). PSAE and other treatment were given via oral gavage for 28 consecutive days. The blood pressure and heart rate were determined using the non-invasive blood pressure monitoring (NIBPM) tail cuff technique and recorded weekly for four weeks. SHR’s blood was collected for the determination of serum NO level using Griess assay. Asymmetric dimethylarginine (ADMA) and arginine levels were determined using HPLC. Results: PSAE shows good in-vitro antioxidant activities with significant reduction of BP and decreased serum ADMA level. Conclusion: PSAE enhances the clearance of ADMA that maintains arginine level, thus increasing the serum NO level, which ameliorate the blood pressure of SHR.

Periodic Assessment Of Antenatal And Post Natal Serum Endothelin1 and Nitric Oxide Levels In Hypertensive Disorders Of Pregnancy

Introduction: Hypertensive Disorder of Pregnancy (HDP) is an independent risk factor of cardiovascular (CVS) disease with persistent endothelial dysfunction, that occurs after the initial insult during pregnancy and persists post partum postulated to be the pathophysiology. Endothelin-1 (ET-1), a potent vasoconstrictor, has been identified as a pivotal mediator in both essential hypertension and HDP. Disturbances in Nitric Oxide (NO) bioavailability found in endothelial dysfunction may increase susceptibility to cardiovascular diseases such as hypertension. Materials and Methods: Thirty six pregnant women at 30-36 weeks period of gestation from the following categories (i) pregnancy induced hypertension (PIH) (ii) chronic hypertension during pregnancy (CH) and (iii) normal pregnant women (Control). Blood pressure indices measurements and sample collection was done at antepartum (30-36 weeks), post partum (8 weeks and 12 weeks). Endothelin-1 was measured using the Human ET-1 (Endothelin-1) ELISA Kit and serum NO was measured using the Nitric Oxide (total) detection kit. Results: All blood pressure indices were significantly higher in HDP patients compared to control during antenatal and post partum periods. Serum ET-1 was significantly higher in patients with HDP compared to control during antenatal until 3 months post partum. This was accompanied by significantly lower levels of serum NO in HDP patients. Conclusion: ET-1 levels in patients with history of HDP irrespective of post partum blood pressure contributes to persistent endothelial dysfunction.

Effect of experimentally induced hypertension on cerebellum of postmenopausal rat.

Cerebellum seems to be a specific target for both the decrease of estrogen and hypertension in menopause. The aim of this study was to investigate the hypertension and menopause-induced changes in rat's cerebellar cortex and the possible mechanisms of these changes. Rats were divided into four groups: the sham-operated control (SC-group), the ovariectomized (OVX-group), the hypertensive (H-group), and the ovariectomized-hypertensive (OVX-H-group) group. The mean arterial pressure (MAP), serum nitric oxide (NO), lipid peroxides and antioxidant catalase enzyme levels were assayed. Cerebellar tissue homogenization for analysis of lipid peroxides, antioxidant catalase enzyme, tumor necrosis factor-α (TNF-α), and estradiol was done. Quantification of adrenomedullin (AM) and interleukin-10 (IL-10) mRNA was also done. Cerebella were processed for histological, immunohistochemical and transmission electron microscopic examination. In the OVX-group, insignificant structural and biochemical changes were observed compared with the SC-group apart from the significantly increased lipid peroxides and decreased NO and catalase levels in serum. The H-group showed an elevated lipid peroxides and TNF-α levels, reduced catalase level, numerous degenerated Purkinje cells, vacuolations of the neuropil, some axonal degeneration, and few ghosts in the granular cell layer (GL). However, in OVX-H-group, oxidative stress, inflammation, and cerebellar damage were exacerbated and cerebellar estrogen was reduced associated with reduction in GL thickness and decreased Purkinje cells number. Most axoplasms had degenerated neurofilaments with abnormal myelination. The immunoexpression of glial fibrillary acidic protein were significantly increased in both OVX-group and H-group and significantly decreased in OVX-H group. Gene expression of AM and IL-10 were increased in cerebellar tissues of H-group compared with the SC-group but it was significantly decreased in OVX-H-group compared with H-group. Taken together, postmenopausal rats with hypertension suffered from structural cerebellar changes than rats with only hypertension or estrogen deficiency separately due to augmentation of the increased oxidative stress markers and the proinflammatory cytokines (TNF-α) with down regulation of the anti-inflammatory cytokine (IL-10) and the blood pressure regulator, AM. These suggested that high blood pressure is a critical factor for postmenopausal cerebellum.

The Effect of Garlic Pills on Serum Nitric Oxide and Preeclampsia Prevention in Healthy Nulliparous Pregnant Women: A Randomized, Controlled Clinical Trial

AbstractThe present study aimed to determine the effect of garlic pills on serum nitric oxide and preeclampsia prevention in healthy nulliparous pregnant women. This randomized clinical trial was conducted among 215 nulliparous pregnant women. The participants were assigned into control and intervention groups. The intervention and control groups received garlic pills and placebo, respectively for 16 weeks from 20 week of gestation. Serum nitric oxide was measured 12 weeks after the intervention. Women were followed up for preeclampsia until childbirth in several visits. Data were analyzed using statistical package for social sciences software. The mean (standard deviation) of serum nitric oxide level was 151.4 (73.1) μmol in the intervention group and 124.1 (44.1) μmol in the control group. There was a significant difference between the two groups (P≤=≤0.029). The prevalence of preeclampsia was 1 (1%) in the intervention group and 5 (5.2%) in the control group. There was no significant difference between the two groups (P≤=≤0.094). The use of garlic pills has a significant effect on the elevation of serum nitric oxide levels. Despite the absence of significant statistical differences between the two groups, garlic pills in comparison with placebo reduced the incidence of preeclampsia.

Oxymatrine ameliorates diabetes-induced aortic endothelial dysfunction via the regulation of eNOS and NOX4.

Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions. In this study, we investigated the effects of OMT on diabetes-associated aortic endothelial dysfunction in a rat model of diabetes and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups: control, diabetic rats, diabetic rats treated with OMT (60, 120 mg/kg per day, by gavage), and diabetic rats treated with metformin (20 mg/kg per day, by gavage). The serum fasting blood glucose, insulin, total cholesterol, triglyceride, and nitric oxide (NO) levels were determined with commercial kits. Biochemical indices reflecting oxidative stress, such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were analyzed with commercial kits. Mitochondrial reactive oxygen species 2',7'-dichlorofluorescein diacetate (DCFH-DA) was measured by fluorescence microscopy. Histological analyses were conducted to observe morphological changes. Western blot analysis was applied to detect the expression levels of eNOS and NOX4. Reverse transcription polymerase chain reaction was used to detect the expressions of eNOS and NOX4 messenger RNA (mRNA). The diabetic rats exhibited markedly reduced body weight and increased plasma glucose levels. Moreover, the diabetic rats showed oxidative stress (significantly increased MDA and decreased SOD, CAT, GSH-Px, and serum NO levels). Hyperglycemia caused significant endothelial injury and dysfunction, including vasodilative and histologic changes in the diabetic rats. The expressions of phospho-eNOS protein and mRNA were significantly decreased, while the NOX4 protein expression was increased in the aortas of the diabetic rats. All of these diabetes-induced effects were reversed by OMT in the diabetic rats. The OMT treatment ameliorates diabetic endothelial dysfunction through enhanced NO bioavailability by upregulating eNOS expression and downregulating expression of NOX4.

Correlation analysis between 25-hydroxyvitamin D3, vitamin B12 and vitamin C and endothelial function of patients with CHD.

The aim of the study was to investigate the correlation between levels of 25-hydroxyvitamin D3, vitamin B12 and C and endothelial function of patients with coronary heart disease (CHD). Forty patients with CHD diagnosed in Shanghai Tenth People's Hospital from May 2016 to April 2017 were selected as the observation group. A total of 45 healthy individuals were selected as the control group. The participants included 54 males and 31 females. General information was collected. Peripheral serum biochemical indicators, levels of 25-hydroxyvitamin D3, vitamin B12 and C, homocysteine (Hcy), nitric oxide (NO) and endothelial NOS (eNOS) were measured. Arterial lesions detected by coronary angiography were recorded and indexes of observation and control group were compared for the correlation analysis. A proportion of hypertensive patients and their body mass index (BMI) were significantly higher in the observation than in the control group (P<0.05). Levels of 25-hydroxyvitamin D3, vitamin B12 and C in peripheral blood of observation were significantly lower than those of the control group (P<0.05). Compared with the control group, incidence of single-branch lesion and non-lesion rate were significantly lower, but incidence of double- and triple-branch lesions were significantly higher in observation than in control group (P<0.05). In addition, the level of Hcy in the observation group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in control group (P<0.05. The correlation analysis revealed that 25-hydroxyvitamin D3 (r=0.792, P<0.01), vitamin B12 (r=0.635, P<0.01) and vitamin C (r=0.703, P<0.01) were negatively correlated with serum NO level. Thus, hypertension, BMI, 25-hydroxyvitamin D3, vitamin B12 and C have independent predictive value for coronary endothelial dysfunction (P<0.05). In conclusion, serum levels of 25-hydroxyvitamin D3, vitamin B12 and C are closely related to vascular endothelial dysfunction in patients with CHD and affect the severity of vascular endothelial dysfunction in patients with CHD.

Isolation and identification of nucleosides/nucleotides raising testosterone and NO levels of mice serum from Chinese chive (Allium tuberosum) leaves.

Our previous study found that Chinese chive could significantly (p<0.01) raise testosterone and nitric oxide (NO) levels in mice serum. However, the specific functional components of this traditional remedy are still unknown. In order to isolate and identify the active constituents from Chinese chive for enhancing testosterone and NO levels, the Chinese chive leaves were extracted by petroleum ether, ethyl acetate, n-butanol and water respectively. Results indicated that the n-butanol extract had a significant effect on NO and testosterone blood levels. Subsequently, n-butanol extract was further isolated by D101 macroporous adsorption and eluted with 50% ethanol and then isolated by Sephadex LH-20 and preparative high-performance liquid chromatography to obtain nucleosides. The fraction eluted with 70% ethanol was further isolated by RP-18 and pre-HPLC to obtain nucleotides. Four novel compounds were identified, and their effects on testosterone and NO levels of male mice were evaluated. Results showed that nucleotides, especially the adenosine in Chinese chive leaves, increased serum testosterone and NO levels in male mice, which had not been reported before. This finding might bring into perspective the treatment strategy for those doctors who treat hormone deficiencies, and might be suitable for using in functional food.

Bipolar Bozukluk Tanılı Hastalarda Nörokognitif İşlevler ile Nitrik Oksit ve Asimetrik Dimetilarjinin Düzeyleri Arasındaki İlişki

Amaç: Bu çalışmada bipolar bozukluk tanısı olan hastalarda bilişsel işlevlerin, serum nitrik oksit (NO) ve asimetrik dimetilarjinin (ADMA) düzeyleri ile ilişkisinin belirlenmesi planlanmıştır.Gereç ve Yöntemler: Çalışmanın örneklemi Afyon Kocatepe Üniversitesi Tıp Fakültesi Psikiyatri Polikliniği tarafından ayaktan takip edilen, DSM-5’e göre bipolar bozukluk tanısı konulmuş ötimik dönemdeki 45 hasta ile yaş, cinsiyet ve eğitim süresi yönünden eşleştirilmiş 45 sağlıklı gönüllüden oluşturuldu. Çalışmaya katılanlara sosyodemografik veri formu, Hamilton Depresyon Derecelendirme Ölçeği ve Young Mani Derecelendirme Ölçeği uygulandı. Nörokognitif fonksiyonlar Sözel Bellek Süreçleri Testi, Wisconsin Kart Eşleştirme Testi, Stroop Testi ve İz Sürme Testi ile incelendi. Serum NO ve ADMA düzeyleri ELİSA kiti kullanılarak ölçüldü.Bulgular: Yaş, cinsiyet ve eğitim durumu açısından eşleştirilmiş iki grup arasında ailevi psikiyatrik soygeçmiş sorgulamasında anlamlı farklılık (p=0,002) olduğu ve hasta grubunun %31’inin ailesinde bipolar bozukluk olduğu tesbit edildi. Hasta grubunun nöropsikolojik test sonuçlarının kontrol grubundan istatistiksel olarak anlamlı derecede düşük olduğu bulundu. Serum ADMA düzeyinin ise hasta grubunda kontrol grubuna göre daha düşük düzeyde olduğu gözlendi (p=0,001). ADMA düzeyi ile kendiliğinden hatırlama puanı (p=0,037), kavramsal düzey tepki yüzdesi (p=0,029), Stroop Test puanları (p=0,043) ve İz Sürme A testi süresi (p=0,002) arasında istatistiki olarak anlamlı ilişki olduğu saptandı.Sonuç: Bu çalışmanın sonuçlarına göre bipolar bozukluk hastalarında bellek, öğrenme, dikkat, işlem hızı, strateji değiştirme, problem çözme gibi bilişsel alanlarda bozulma olduğu fakat bu bozulmanın serum NO düzeyi ile ilişkisi olmadığı fakat kendiliğinden hatırlama, kavramsal tepki yüzdesi, Stroop Testi tamamlama süresi, İz Sürme A testi süresi puanlarının ADMA ile ilişkisi olduğu belirlenmiştir.

Effects and mechanisms of Danshen-Shanzha herb-pair for atherosclerosis treatment using network pharmacology and experimental pharmacology

Ethnopharmacological relevanceThe danshen (the root of Salvia miltiorrhiza Bge.)-shanzha (the fruit of Crataegus pinnatifida Bge. var. major N.E.Br.) (DS) herb combination is a commonly used traditional Chinese medicine with cardiovascular disease (CVD) treatment potential. Materials and methodsIn this study, we investigated the anti-atherosclerotic effects and mechanisms of DS by the integration of network pharmacology and polypharmacology. Eight main components were selected for target fishing by PharmMapper. ResultsThe network pharmacological study indicated that DS may target 41 proteins and 16 pathways associated with inflammation, lipid metabolism and endothelial protection, which indicates that DS probably adjusts these processes as part of its anti-atherosclerotic activities. Furthermore, this hypothesis was verified by polypharmacology using an atherosclerotic model. Histopathological examination showed that DS inhibited pathological changes in the arteries of atherosclerotic rats and reduced the intima-media thickness (IMT). DS significantly reduced the levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) and increased the high-density lipoprotein-cholesterol (HDL-C) level in the blood. DS also decreased the concentrations of interleukin (IL)-1β and IL-18, indicating anti-inflammation activity. In addition, DS increased the serum levels of nitric oxide (NO) and 6-keto-prostaglandin F1α (6-keto-PGF1α) and decreased the serum levels of endothelin (ET) and thromboxane B2 (TXB2), indicating an endothelial protective effect. ConclusionsIn conclusion, DS has an anti-atherosclerotic ability to lower lipid concentrations and to protect endothelial function, and it also has anti-inflammatory activity.

Polymorphisms of endothelial nitric oxide synthase and hypoxia-inducible factor 1 alpha genes play a role in susceptibility to coronary artery disease

Objective: Genetics is a known factor in the susceptibility to cardiovascular disease. In this study, polymorphisms of endothelial nitric oxide synthase (eNOS) (T876C and G894T) and hypoxiainducible factor 1 (HIF1) (rs10873142 and rs41508050) in coronary artery disease were compared with healthy subjects, and the relationship between these mutations and risk of coronary artery disease (CAD) was assessed.&#x0D; Methods: Blood samples were collected from 138 patients with obstructive CAD and 115 healthy subjects. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP), Griess test, and enzyme-linked immunosorbent assay (ELISA) were used to measure serum nitric oxide (NO) and paraoxonase antioxidant. Independent t-test was used to examine the relationship between variables.&#x0D; Results: There was no significant difference between genotype frequency in healthy subjects and patients for eNOS and HIF1 alpha polymorphisms. There was no significant difference between these polymorphisms and age, sex, hypertension and lipidemia. Furthermore, the difference in mean serum levels of NO in different genotypes of the G894T gene was not significant between the patient and control groups. However, the difference in mean serum NO levels in different genotypes of the T786C gene was significant between the patient and control groups such that minimum and maximum serum NO levels were observed in individuals bearing TT and TC genotypes, respectively. The difference in mean serum NO levels was higher in patients than in controls, and was statistically significant.&#x0D; Conclusions: The results suggest that the T876C polymorphism could be associated with low serum NO level and implicated as a risk factor for developing CAD. Furthermore, our findings indicate that genetics may not be involved in susceptibility to CAD; however, further comprehensive studies are required.

Myocardial injury induced by scorpion sting envenoming and evidence of oxidative stress in Egyptian children

In the present study, 45 children in Upper Egypt (less than 16 years old) were admitted to the Pediatric Intensive Care Unit for scorpion envenomation (SE). They were compared with 30 apparently healthy children of matching age and sex as controls. Out of the studied victims, 35 children (78%) showed signs of severe envenomation, while 10 victims (22%) showed signs of mild envenomation. The case fatality was 33%. The serum levels of cardiac markers, cardiac troponin T (cTnT) and I (cTnI), as well as the enzymatic activities of creatine kinase-MB (CPK-MB) and lactate dehydrogenase (LDH) were determined for both victims and controls. In addition, the serum levels of oxidative stress markers, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and zinc (Zn) were measured. Electrocardiography and echocardiography were done. All the envenomed victims showed significantly higher mean values of cTnT, cTnI, CPK-MB and LDH than control group. These cardiac markers were elevated in severe cases and in non survivors in comparison with mild cases and survivors respectively. Furthermore, the serum levels of NO and MDA were significantly higher while the serum levels of SOD, GSH and Zn were significantly lower in all envenomed victims than the controls (p < 0.05 for all). There were no significant differences in the serum levels of oxidative stress markers among severe and mild cases or between survivors and non survivors victims. There were no significant correlations between the serum levels of cardiac markers and the oxidative stress markers in envenomed victims. In conclusions, oxidative stress occurs in scorpion envenomed children, but does not determine prognosis. Cardiac markers, but not the oxidative stress, remain the most important determining factor for the severity and the outcome of SE.