Serum Nitric Oxide Concentration Research Articles

N-Acetylcysteine Supplementation Improves Testicular Haemodynamics, Testosterone Levels, Seminal Antioxidant Capacity and Semen Quality in Heat-Stressed Goat Bucks.

Heat stress (HS) disrupts testicular homeostasis because of oxidative stress. N-acetylcysteine (NAC) is a thiol compound with antioxidants, anti-inflammatory and anti-apoptotic properties. As a sequel, this research aimed to assess the ameliorative effects of NAC supplementation on the reproductive performance of goat bucks kept under environmental HS. Primarily, Doppler examination as well as semen collection and evaluation were conducted on 12 mature bucks for 2 weeks (W) as pre-heat stress control (W1 and W2) during winter (February 2023). The temperature-humidity index (THI) was 63.4-64.3 (winter season). Then during summer HS conditions (from the beginning of July till the end of August 2023) bucks were assessed before NAC supplementation (W0), afterwards they were arbitrarily assigned into two groups. The control group (CON; n = 6) received the basal diet while the NAC group (n = 6) received the basal diet in addition to oral NAC daily for 7 weeks (W1-W7). The THI was 78.1-81.6 (summer season). Testicular blood flow parameters, serum concentration of nitric oxide (NO) and testosterone were measured. Additionally, total antioxidant capacity (TAC) and malondialdehyde (MDA) content in seminal plasma and semen quality parameters were evaluated. There were marked reductions (p < 0.05) in the resistive index (RI; W1, W4 and W5), pulsatility index (PI; W2 and W4-W7), and systolic/diastolic ratio (S/D; W4-W7) in the NAC group compared to the CON group. Furthermore, testosterone and NO levels were higher (p < 0.01 and p < 0.05, respectively) in the NAC group (W2, W3, W5 and W3-W5, respectively). Seminal plasma TAC increased (p < 0.05) and MDA decreased (p < 0.05) in the NAC group (W2, W4 and W5) compared to the CON group. Moreover, there were marked improvements (p < 0.05) in semen quality parameters (mass motility, total motility, viability and normal morphology) in the NAC group. In conclusion, oral NAC supplementation could be used to enhance the reproductive performance of goat bucks during HS conditions which is supported by remarkable enhancement in testicular haemodynamics, NO, testosterone levels and semen quality parameters.

Effect of diets containing probiotic yeast Cystobasidium benthicum and fruit Cyrtocarpa edulis on growth and immune parameters of Nile tilapia (Oreochromisniloticus)

This study investigates Cystobasidium benthicum (Cb) probiotic yeast and Cyrtocarpa edulis (Ce) fruit dietary effects, single (0.5 %) or combined (Cb:Ce, 0.25:0.25 %), on growth performance, humoral immunity in serum and skin mucus, and intestinal morphology of Nile tilapia (Oreochromis niloticus) after 14 and 28 days. The Cb group presented the highest (P < 0.05) specific growth rate, weight gain, and absolute growth rate with respect to the control group. Immunological assays indicated that Cb, Ce and Cb:Ce groups increased serum nitric oxide concentration compared to the control group (P < 0.05). Cb and Cb:Ce groups showed the highest serum myeloperoxidase enzyme activity at day 14 and 28, respectively (P < 0.05); whereas, Cb:Ce group had the highest (P < 0.05) myeloperoxidase activity in skin mucus. The superoxide dismutase enzyme activity was unaffected. On day 28, Cb, Ce, and Cb:Ce groups showed higher and lower (P < 0.05) catalase enzyme activity in serum and skin mucus, respectively, compared with the control group. Only the Cb group had higher (P < 0.05) total protein concentration in serum (day 14) and skin mucus (day 14 and 28) with respect to the control group. The lysozyme activity in serum (day 28) and skin mucus (day 14) was higher (P < 0.05) in the Cb group compared to the control group. Only the skin mucus of Ce group showed bactericidal activity against Aeromonas dhakensis (P < 0.05). Histological studies indicated that Cb and Cb:Ce groups increased microvilli height, and Cb, Ce and Cb:Ce augmented goblet cell area at day 14 compared to the control group (P < 0.05). At day 28, microvilli height was higher in all groups and the number of intraepithelial leukocytes increased in Cb and Ce groups with respect to the control group (P < 0.05). The ex vivo assay revealed that A. dhakensis in leukocytes decreased cell viability similar to the control group (P < 0.05). A principal component analysis (PCA) confirmed the results. In conclusion, C. benthicum in the diet was the best supplement to improve the growth and immunity of Nile tilapia.

Effects of different nitric oxide synthases on pulmonary and systemic hemodynamics in hypoxic stress rat model.

Under hypoxia, exaggerated compensatory responses may lead to acute mountain sickness. The excessive vasodilatory effect of nitric oxide (NO) can lower the hypoxic pulmonary vasoconstriction (HPV) and peripheral blood pressure. While NO is catalyzed by various nitric oxide synthase (NOS) isoforms, the regulatory roles of these types in the hemodynamics of pulmonary and systemic circulation in living hypoxic animals remain unclear. Therefore, this study aims to investigate the regulatory effects of different NOS isoforms on pulmonary and systemic circulation in hypoxic rats by employing selective NOS inhibitors and continuously monitoring hemodynamic parameters of both pulmonary and systemic circulation. Forty healthy male Sprague-Dawley (SD) rats were randomly divided into four groups: Control group (NG-nitro-D-arginine methyl ester, D-NAME), L-NAME group (non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester), AG group (inducible NOS inhibitor group, aminoguanidine), and 7-NI group (neurological NOS inhibitor, 7-nitroindazole). Hemodynamic parameters of rats were monitored for 10 min after inhibitor administration and 5 min after induction of hypoxia [15% O2, 2200 m a. sl., 582 mmHg (76.5 kPa), Xining, China] using the real-time dynamic monitoring model for pulmonary and systemic circulation hemodynamics invivo. Serum NO concentrations and blood gas analysis were measured. Under normoxia, mean arterial pressure and total peripheral vascular resistance were increased, and ascending aortic blood flow and serum NO concentration were decreased in the L-NAME and AG groups. During hypoxia, pulmonary arterial pressure and pulmonary vascular resistance were significantly increased in the L-NAME and AG groups. This compensatory mechanism activated by inducible NOS and endothelial NOS effectively counteracts the pulmonary hemodynamic changes induced by hypoxic stress. It plays a crucial role in alleviating hypoxia-induced pulmonary arterial hypertension.

Microcirculatory visualization and metabolomics of Dalbergia cochinchinensis in ameliorating coronary microvascular dysfunction in rats

This study employed microcirculation visualization and metabolomics methods to explore the effect and possible mechanism of Dalbergia cochinchinensis in ameliorating coronary microvascular dysfunction(CMD) induced by microsphere embolization in rats. Sixty SPF-grade male SD rats were randomized into sham, model, and low-, medium-, and high-dose [1.5, 3.0, and 6.0 g·kg~(-1)·d~(-1), respectively] D. cochinchinensis water extract groups. The rats in sham and model groups were administrated with equal volume of normal saline by gavage once a day for 7 consecutive days. The rat model of CMD was prepared by injecting polyethylene microspheres into the left ventricle, while the sham group was injected with an equal amount of normal saline. A blood flow meter was used to measure blood flow, and a blood rheometer to measure blood viscosity and fibrinogen content. An automatic biochemical analyzer and reagent kits were used to measure the serum levels of myocardial enzymes, glucose, and nitric oxide(NO). Hematoxylin-eosin(HE) staining was used to observe the pathological changes of myocardial tissue. DiI C12/C18 perfusion was used to infuse coronary microvessels, and the structural and morphological changes were observed using a confocal laser scanning microscope. AngioTool was used to analyze the vascular area, density, radius, and mean E lacunarity in the microsphere embolization area, and vascular blood flow resistance was calculated based on Poiseuille's law. Non-targeted metabolomics based on high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed screen potential biomarkers and differential metabolites regulated by D. cochinchinensis and the involved metabolic pathways were enriched. The pharmacodynamic results showed that compared with the model group, D. cochinchinensis significantly increased mean blood flow, reduced plasma fibrinogen content, lowered the levels of myocardial enzymes such as creatine kinase(CK), creatine kinase-MB(CK-MB), and lactate dehydrogenase(LDH), alleviate myocardial injury, and protect damaged myocardium. In addition, D. cochinchinensis significantly increased serum NO content, promoted vascular smooth muscle relaxation, dilated blood vessels, lowered serum glucose(GLU) level, improved myocardial energy metabolism, and alleviated pathological changes in myocardial fibrosis and inflammatory cell infiltration. The results of coronary microcirculation perfusion showed that D. cochinchinensis improved the vascular morphology, increased the vascular area, density, and radius, reduced vascular mean E lacunarity and blood flow resistance, and alleviated vascular endothelial damage in CMD rats. The results of metabolomics identified 45 differential metabolites between sham and model groups, and D. cochinchinensis recovered the levels 25 differential metabolites, which were involved in 8 pathways including arachidonic acid metabolism, arginine biosynthesis, and sphingolipids metabolism. D. cochinchinensis can ameliorate coronary microcirculation dysfunction caused by microsphere embolization in rats, and it may alleviate the pathological changes of CMD rats by regulating inflammatory reaction, endothelial damage, and phospholipid metabolism.

Risk of endothelial dysfunction in streptozotocin-induced diabetic Sprague-Dawley rats: Nitric oxide in focus

Endothelial dysfunction in diabetes manifests in part as reduction of nitric oxide (NO) bioavailability, which leads to inadequate relaxation of the vascular smooth muscle and a disparity between the vasoconstrictive and vasorelaxant intracellular pathways which favours a rise in vasoconstriction. In this current work, we evaluated serum Nitric oxide (NO) concentration and the activity of Nitric oxide synthase (NOS) in streptozotocin-induced diabetic male and female rats' serum. Our results showed initial and final fasting blood glucose concentration 5.30±0.16mmol/l and 5.24±.015mmol/l versus 5.68±0.18mmol/l and 5.43±0.15mmol/l in male and female controls. Among the diabetic rats, the initial and final fasting blood glucose concentration was 17.50±1.91mmol/l and 15.68±2.84mmol/l versus 20.50±4.76mmol/l and 19.40±4.13mmol/l in male and female rats respectively. NO concentration was 106.12±7.23μmol/l and 131.81±12.54 μmol/l in male and female control rats compared to 52.38±3.01μmol/l and 65.29±16.19 μmol/l in male and female diabetic rats respectively. Serum activity of NOS were 133.72±10.92μIU/l and 156.06±18.22 μIU/l in control male and female rats compared to 98.01±1.48 μIU/l, 78.89±8.39μIU/l in diabetic male and female rats respectively. The difference in both NO concentration and NOS activity was significant between diabetics and non-diabetic rats as well as between male and female diabetics rats (p&lt; 0.05). The endothelial dysfunction in diabetic animals regardless of gender may be an initial pointer to upcoming pathogenesis and we recommend routine evaluation of NO concentration and NOS activities among diabetics.

Effects of N-acetylcysteine on oxidative stress biomarkers, depression, and anxiety symptoms in patients with multiple sclerosis.

N-acetylcysteine (NAC), a thiol-containing antioxidant and glutathione (GSH) precursor, attenuates oxidative stress, and possibly improves psychiatric disorders. This study aimed to evaluate the effects of oral NAC on oxidative stress, depression, and anxiety symptoms in patients with multiple sclerosis (MS). This clinical trial was conducted on 42 MS patients randomly assigned to intervention (n = 21) and control (n = 21) groups. The intervention group received 600 mg of NAC twice daily for 8 weeks, and the control group received a placebo with the same prescription form. An analysis of serum malondialdehyde (MDA), serum nitric oxide (NO), and erythrocyte GSH was carried out on both groups, along with a complete blood count. The Hospital Anxiety and Depression Scale (HADS) was used to assess symptoms of depression (HADS-D) and anxiety (HADS-A). Compared to the control group, NAC consumption significantly decreased serum MDA concentrations (-0.33 [-5.85-2.50] vs. 2.75 [-0.25-5.22] μmol/L; p = 0.03) and HADS-A scores (-1.6 ± 2.67 vs. 0.33 ± 2.83; p = 0.02). No significant changes were observed in serum NO concentrations, erythrocyte GSH levels, and HADS-D scores (p > 0.05). Based on the findings of the present study, NAC supplementation for 8 weeks decreased lipid peroxidation and improved anxiety symptoms in MS patients. The aforementioned results suggest that adjunctive therapy with NAC can be considered an effective strategy for MS management. Further randomized controlled studies are warranted.

The role of nutritional-immunological indices in estimating serum LPS and antioxidant enzyme activity and sepsis status in female dogs with pyometra caused by E. coli

The aim of this study was to diagnose pyometra and related sepsis status using cost-effective nutritional-immunological indices, antioxidants, and toxin levels in dogs and to investigate the utility of the indices in predicting toxin and antioxidant status. A total of 29 dogs were enrolled into the present study. Among these, 9 female dogs in their diestrus stages, were allocated for elective ovariohysterectomy. The pyometra group was also separated into two subgroups as Sepsis (+) and Sepsis (-). Blood samples were collected into two tubes containing EDTA for hematological analysis; without anticoagulant for serum progesterone, LPS concentration, and antioxidant levels at the time of diagnosis. Bacteriological and tissue samples of the uterus were collected after the ovariohysterectomy. Antioxidant activity, progesterone, and toxin concentration were determined by using commercial ELISA kits. Statistical analyses were performed using Stata version 16.1 and MedCalc 16 statistical software. Receiver operating characteristics curves were used for the threshold for evaluating pyometra and sepsis status. Pairwise comparisons were carried out of the area under the curve (AUC) for thresholds of nutritional immunologic indices (hemoglobin, albumin, lymphocyte, platelet (HALP) score; prognostic nutritional index (PNI); Albumin hemoglobin index (AHI)), serum LPS and antioxidant activity. Linear regression model was used for the estimation of serum LPS and antioxidant activity by using indices. Mean serum progesterone, LPS concentrations, and Nitric Oxide (NO) production were greater, while serum superoxide dismutase (SOD), tissue SOD, and glutathione peroxidase (GPx) activities were lower in dogs with pyometra. All nutritional-immunologic indices were lower in pyometra cases. Nutritional-immunologic indices (AUC of HALP:0.759; PNI:0.981; AHI 0.994), NO (AUC: 0.787) and SOD (AUC: 0.784) levels were useful for pyometra diagnosis. AHI and LPS were useful for the determination of sepsis status with the AUC values of 0.850 and 0.740, respectively. While AHI was useful for the estimation of serum LPS and NO concentration (p < 0.001), PNI was useful for serum SOD concentration (p = 0.003). In conclusion, PNI, HALP and AHI can be used in the diagnosis of pyometra, however, only AHI and LPS levels can be used in the diagnosis of sepsis. SOD and NO can be used to determine pyometra but have no effect on determining sepsis status. Additionally, the estimation of the levels of serum LPS, NO, and SOD activities can be done using the AHI and PNI values.

Does Intense Endurance Workout Have an Impact on Serum Levels of Sex Hormones in Males?

The benefits of physical activity and sports are widely known and proved to be crucial for overall health and well-being. In this research, the authors decided to measure the impact of endurance training in a professional male rowing team on the serum concentration levels of testosterone, estradiol, sex hormone binding globulin (SHBG) and nitric oxide (NO) and apolipoprotein A1 (Apo-A1). Proper levels of the serum concentration are necessary in order to maintain physical effectiveness. Authors analyzed the data and reviewed the former conterminous articles to find the possible mechanisms leading to changes of serum concentration of certain hormones and molecules. The direct effect of physical activity was a decrease in testosterone serum concentration (from 7.12 ± 0.4 to 6.59 ± 0.35 (ng/mL)), sex hormone binding globulin serum concentration (from 39.50 ± 2.48 to 34.27 ± 2.33 (nmol/L)), nitric oxide serum concentration (from 440.21 ± 88.64 to 432 ± 91.89 (ng/mL)), increase in estradiol serum concentration (from 78.2 ± 11.21 to 83.01 ± 13.21 (pg/mL)) and no significant increase in Apo-A1 serum concentration (from 2.63 ± 0.2 to 2.69 ± 0.21 (mg/mL)). Low testosterone concentration in OTS may be a consequence of increased conversion to estradiol, because gonadotropic stimulation is maintained. Apo-A1 serum concentration was measured due to a strong connection with testosterone level and its possible impact of decreasing cardiovascular risk.

Serum nitric oxide concentration in generalized chronic and aggressive periodontitis in the Mexican population is not related to the severity of the disease

Introduction: Periodontitis is an inflammatory disease that affects the supporting tissues of teeth, the effects of excess of nitric oxide, may contribute to the symptoms of periodontitis. Objective: To determine the serum nitric oxide concentration in generalized chronic and aggressive periodontitis patients and to compare it with a healthy subject group from the Mexican population. Materials and methods: A case and control study was performed. Sixty-nine individuals were recruited from the Clínica de Posgrado de Periodoncia of the Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, México. Patients with clinical features of generalized chronic periodontitis (GCP group, n=19), generalized aggressive periodontitis (GAP group, n=11), and a group of healthy subjects (HS group, n=39) were included in the study. Informed consent was obtained from each subject, and serum nitric oxide concentration was measured by an enzyme-linked immunosorbent assay. Results: Nitric oxide concentration in the study groups was greater in the GCP group (462.57 ± 16.57 μmol/L) than in the GAP group (433.84 ± 18.61 μmol/L) and the HS group (422.46 ± 12.07 μmol/L). A comparison using Student’s t-test (one-tailed) between healthy subjects and generalized chronic periodontitis showed borderline significance (p<0.04), whereas no significant differences were observed in HS and GAP groups, with a p-value of 0.64, and the GAP vs. GCP p-value was 0.33. Conclusion: The serum nitric oxide concentration observed in the present study suggests that nitric oxide plays a major role in the inflammatory process, which cannot necessarily be linked to the severity of the disease and periodontal tissue destruction.

Radio-adaptive Response Induced by Low-dose Ionizing Radiation in Innate Immunity for Radiotherapy.

Radio-adaptive response (RAR) is a mechanism by which low doses of ionizing radiation (IR) protect cells from subsequent high doses. This study aimed to compare the immuno-radiological effects of 0.25, 0.5, and 5 Gy to 0.25 or 0.5 Gy as priming and 5 Gy as challenging doses. Thirty-five rats were irradiated whole-body with 0.25 and 0.5 Gy followed by 5 Gy, and the same single IR doses with non-irradiated animals serving as controls. Serum interferon-gamma (INF-γ), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and malondialdehyde (MDA) levels were measured 4 d post both priming and challenge doses. A 0.25-Gy priming dose significantly (P < 0.05) reduced serum TNF-α, MDA, and NO levels compared to all single-irradiated groups. Surprisingly, there was no difference in IFN-γ serum levels between the RAR-induced and non-irradiated groups (P ≥ 0.05). Compared to the same low priming dose (0.25 and 0.5 Gy), the effect of the challenging dose (5 Gy) remains unchanged or decreases. Serum IFN-γ, MDA, and NO concentrations, on the other hand, were significantly (P < 0.05) lower in the 0.5 Gy pre-challenging dose, whereas IL1β had no effect (P ≥ 0.05) compared to 5 Gy alone. The post-RAR group had significantly (P < 0.05) lower oxidative stress indicators than the other irradiation groups. The findings suggested that priming with low IR could help mitigate the negative effects on the hematopoietic system. Finally, RAR has significantly impacted endogenous cytokines, oxidative stress biomarkers, and lipid peroxidation parameters. RAR can improve patients' radiological safety profiles by mitigating adverse radiotherapy effects.

Magnesium ions improve vasomotor function in exhausted rats.

To observe the effect of magnesium ion on vascular function in rats after long-term exhaustive exercise. Forty male SD rats were divided into two groups, the control group (CON group, n = 20) and the exhaustive exercise group (EEE group, n = 20). Exhausted rats performed 1W adaptive swimming exercise (6 times/W, 15min/time), and then followed by 3W formal exhaustive exercise intervention. Hematoxylin and eosin (HE) staining was used to detect the morphological changes of rat thoracic aorta. The contents of interleukin-1 β (IL-1β) and tumor necrosis factor-α (TNF-α) in serum of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and endothelin 1 (ET-1) in serum of rats were determined by biochemical kit. Vascular ring test detects vascular function. Compared with the CON group, the smooth muscle layer of the EEE group became thicker, the cell arrangement was disordered, and the integrity of endothelial cells was destroyed; the serum Mg2+ in EEE group was decreased; the serum levels of IL-1β, TNF-α, MDA and ROS in EEE group were significantly higher than those in the CON group (P are all less than 0.05); the serum NO content in EEE group was significantly decreased, and the ratio of NO/ET-1 was significantly decreased. In the exhaustion group, the vasoconstriction response to KCl was increased, and the relaxation response to Ach was weakened, while 4.8mM Mg2+ could significantly improve this phenomenon (P are all less than 0.01). The damage of vascular morphology and function in rats after exhaustion exercise may be related to the significant increase of serum IL-1β, TNF-α, ROS, MDA and ET-1/NO ratio in rats after exhaustion exercise, while Mg2+ can significantly improve the vasomotor function of rats after exhaustion exercise.

Relationship between serum nitric oxide of patients with thyroid disorders and metabolic syndrome indices and nitrate concentration of water

This case–control study aimed to assess the effect of drinking water nitrate on serum nitric oxide concentration and the risk of metabolic syndrome (MetS) in the population in the Middle East. The study included 50 control and 50 thyroid disorder cases who were referred to two medical centers in 2021. In this study, serum nitric oxide concentration, drinking water nitrate, and metabolic syndrome components were measured in the two groups. The results showed there was a statistically significant difference between serum NO in the case and control groups (p-value < 0.001). There was a positive correlation between the concentration of nitrate in drinking water and serum nitric oxide in the case and control groups; however, this relationship was not significant statistically. A statistically significant difference was found between serum nitric oxide and systolic blood pressure in the cases (p-value < 0.05), but there was no significant difference between MetS and nitric oxide. Therefore, we concluded that the relationship between nitric oxide and nitrate in consuming water should be determined in thyroid patients. In addition to their water consumption, it is better to study the nitrate of foods, especially vegetables.

Clinicopathological and biochemical evaluation of Feline Infectious Peritonitis in Turkish Van cats

This study was performed to investigate serum homocysteine and nitric oxide levels in cats with Feline Infectious Peritonitis and present some biochemical and pathological alterations related to the disease. The animal material of this study consisted of thirty Turkish Van Cats of different ages and genders that were definitely diagnosed with the disease by post-mortem examinations and immunohistochemistry. The control group consisted of 6 healthy Turkish Van Cats of different ages and genders that were brought for routine clinical examination. Cats in the study group had clinical findings such as loss of appetite, weight loss, high fever, fever not reduced despite antibiotics, jaundice, dehydration, vomiting, respiratory system symptoms, anemia, nervous findings, uveitis, and ascites. These cats were monitored and following the death, post-mortem examinations were performed and cases with a definitive diagnosis were included in the study. Among the cats consisting study group, while 25 had the dry form of the disease, 5 had wet form. According to the hematological results, there was a statistically significant reduction in platelet counts. The biochemical results showed statistically significant alterations that creatinine, aspartate aminotransferase, alkaline phosphatase, creatine kinase myocardial band, homocysteine, and nitric oxide concentrations were higher than the control group. Besides albumin concentrations were lower and the albumin/globulin ratio was 0.53. As a result; this is the first detailed study in Turkish Van Cats with Feline Infectious Peritonitis that evaluated clinical, hematological, biochemical, and pathological findings. Furthermore, serum homocysteine and nitric oxide levels were evaluated for the first time in cats with vasculitis which is the most important complication of the disease. It is concluded that the evaluation of serum homocysteine and nitric oxide concentrations in Feline Infectious Peritonitis may assist the antemortem diagnosis of the disease.

Effect of arginine supplementation on the production of milk fat in dairy cows.

Arginine, one of the conditionally essential AA, has been reported to affect fat synthesis and metabolism in nonruminant animals by influencing adenosine monophosphate activated protein kinase (AMPK) in some organs. In dairy cows, the effect of Arg on milk fat production is not clear, and any potential mechanism that underlies the effect is unknown. We tested the hypothesis that Arg infusion would improve the production of milk fat, and explored possible mechanism that might underlie any effect. We used 6 healthy lactating cows at 20 ± 2 d in milk, in fourth parity, with a body weight of 508 ± 14 kg, body condition score of 3.0 ± 0, and a milk yield of 30.6 ± 1.8 kg/d (mean ± standard deviation). The cows were blocked by days in milk and milk yield and each cow received 3 treatments in a replicated 3 × 3 Latin square design, with each of the experimental periods lasting 7 d with a 14-d washout between each period. The treatments, delivered in random order, were (1) infusion of saline (control); (2) infusion of 0.216 mol/d of l-Arg in saline (Arg); (3) infusion of 0.868 mol/d of l-Ala in saline (the Arg and Ala treatments were iso-nitrogenous) through a jugular vein. On the last day of each experimental period, blood was sampled to measure insulin, nitric oxide, glucose, and nonesterified fatty acid, and the liver and mammary gland were biopsied to measure the expression of genes. Milk yield was recorded, and milk fat percentage was measured daily during each of the experimental periods. The yield and composition of fatty acid (FA) in milk was measured daily on the last 3 d during each of the experimental periods. The data were analyzed using a mixed model with treatment as a fixed factor, and cow, period, and block as random factors. The daily milk yield and milk fat yield when the cows were infused with Arg were 2.2 kg and 76 g, respectively, higher than that in control, and 1.8 kg and 111 g, respectively, higher than that in Ala. When the cows were infused with Arg they had higher concentration and yield of de novo synthesized FA, than when they received the control or Ala infusions, although milk fat percentage, daily feed intake, and the digestibility of nutrients were not affected by treatment. The serum concentration of nitric oxide and insulin were higher during Arg than during control or Ala, with no difference between control and Ala. In the liver, the expression of the genes coding for AMPK (PRKAA1, PRKAB1, and PRKAG1) and genes related to the oxidation of FA were higher during Arg than during control or Ala, whereas in the mammary gland the expression PRKAB1 was lowest, and the expression of genes involved in the synthesis of milk fat were highest, during Arg infusion. The results suggest the intravenous infusion of Arg enhanced the production of milk fat by promoting the de novo synthesis of FA and increasing milk yield.

Investigation of the Effect and Possible Mechanism of Antihypertensive Activity of Lycopene-rich Extract of Solanum lycopersicon in Wistar Rats

Background and Aim: Hypertension is a common debilitating illness among people in both developed and developing countries. This study investigated the effect and possible mechanism of the antihypertensive activity of lycopene-rich extract of Solanum lycopersicon (LRESL) on Wistar rats. Methods: Sixty hypertensive Wistar rats were divided into seven experimental groups viz: Group A served as a normotensive group and received food and clean distilled water ad libitum. Group B was the hypertensive untreated group; Groups C-E served as hypertensive group administered with 100, 200, and 400 mg/kg LRESL, respectively. While group F was hypertensive and received 10 mg/kg amlodipine and group G received 200 mg/kg of LRESL+0.5 mg/kg Lisinopril respectively. Results: There was a statistical significant decrease (P&lt;0.05) in the systolic and diastolic blood pressure and the decrease was in a dose-dependent manner. The heart rate showed no statistical significant difference among the groups. The total cholesterol (TC) increased in the positive and normal control compared to other groups. There was a significant decrease in the triglyceride (TG), low density lipoprotein cholesterol (LDL-C) in all hypertensive treated groups. The decrease in the LRESL treated groups was in a dose-dependent manner and there was no significant difference between the groups compared to the normotensive and positive control. Moreover, the high density lipoprotein cholesterol (HDL-C) had a significant reverse effect of the LDL-C as there was a significant increase (P&lt;0.05) in HDL-C and the increase was more significant in group E and G respectively. The serum cardiac arginase (SCAr) activity also decreased significantly (P&lt;0.05) in all groups except group B compared to the normotensive and positive control groups and in a dose-dependent manner. The serum nitric oxide (SNO) concentration also increased in all test groups in a dose-dependent pattern except the positive control group. Conclusion: This study suggests that LRESL has an antihypertensive property and elicited this through multiple mechanisms involving a decrease in SCAr, LDL-C, body weight and marked elevation of SNO and could be used as a novel compound channeled into the production of antihypertensive drugs.

Efficacy of catgut-embedding therapy at “five neck points” on cervical spondylotic arteriopathy and effects on hemodynamics: A randomized clinical trial “颈五针”穴位埋线治疗椎动脉型颈椎病疗效及对血流动力学的影响-随机临床试验

ObjectiveTo observe the effect of catgut-embedding therapy at five neck points in the treatment of cervical spondylotic arteriopathy (CSA) and analyze its effects on the hemodynamics of patients with CSA. MethodsUsing the computer randomization method, 72 patients with CSA were divided into a catgut-embedding therapy group (n = 36, none dropped out) and a western medication group (n = 36, none dropped out). In the catgut-embedding therapy group, the therapy was applied to five neck points, i.e. bilateral Jĭngjiājĭ (颈夹脊) at C5, bilateral Jĭngjiājĭ (颈夹脊) at C6, and Dàzhuī (大椎GV14) once a week. One 3-week treatment session was required. In the western medication group, flunarizine hydrochloride 5 mg capsules were administered orally once daily for 3 weeks. Efficacy was assessed before and after 3 weeks treatment using a functional evaluation scale for cervical spondylotic arteriopathy (FS-CSA). Changes in vertebral-basilar arterial hemodynamics, serum nitric oxide (NO) level, and plasma endothelin (ET) level were detected. ResultsEfficacy was assessed when the treatment session was completed. The total efficacy rate was significantly higher in the catgut-embedding therapy group (86.1%) than in the western medication group (61.1%; P < 0.01). The after treatment FS-CSA score was reduced compared with baseline score in both groups (P < 0.05), and the reduction in the catgut-embedding therapy group was superior to that in the Western medication group (P < 0.05). Compared with baseline, the flow velocity and pulsatility index of the bilateral vertebral and basilar arteries increased at each period in both groups (P < 0.05) except for the left systolic velocity of the vertebral artery after treatment. The increase in the catgut-embedding therapy group was greater than that in the western medication group (P < 0.05). After treatment, the serum NO concentration was increased and the plasma ET concentration was reduced compared to baseline in both groups (P < 0.05), while the improvements in the catgut-embedding therapy group were superior to those in the western medication group (P < 0.05). ConclusionThe clinical efficacy in the catgut-embedding therapy group was superior to that in the western medication group. Catgut-embedding therapy at five neck points may effectively improve psychological and functional conditions, promote vertebral basilar arterial supply, and relieve clinical symptoms in patients with CSA.

β-1,3/1,6-D-glucan of Mycelia Extract Posses Renal Protection Potential and Reduces Nitric Oxide in Obese Subjects

BACKGROUND: Obesity has been widely reported to be associated with loss of kidney function. The efficacy of β-1,3/1,6-D-glucan as a traditional medicine for the improvement of inflammation and vascular status in obesity has known. However, there have been no further studies that prove the effect of β-1,3/1,6-D-glucan in inhibiting kidney injury as an impact of chronic inflammation exposure on obesity. This study aimed to investigate the impact of β-1,3/1,6-D-glucan from mycelia extract supplementation on renal function improvement based on serum nitric oxide (NO), ureum, and creatinine levels.METHODS: This was a randomized control trial study involving 69 obese subjects treated with or without β-1,3/1,6-D-glucan supplementation. The serum NO, ureum, and creatinine levels of the subjects were measured at baseline and post-treatment using enzyme-linked immunosorbent assay (ELISA) and then statistically analyzed with paired T-test.RESULTS: Although slightly decrease, no significant difference was found between the ureum and creatinine level at the baseline and and post-treatment (p=0.806, p=0.306, respectively) after β-1,3/1,6-D-glucan supplementation. Serum NO levels significantly decrease after treatment of β-1,3/1,6-D-glucan (p&lt;0.001).CONCLUSION: Current study concludes that β-1,3/1,6-D-glucan from mycelia extract does not significantly lower urea and creatinine level, however, significantly able to reduce the serum NO concentration in obese subjects. Therefore, β-1,3/1,6-D-glucan from mycelia extract might have the renal protection potential in obesity.KEYWORDS: β-1,3/1,6-D-glucan, Ganoderma lucidum, renal function improvement, obesity

Effect of Flavonoid Rich Fraction of Coriandrum sativum Leaf on Lipid Profile, Nitric Oxide, Ang II and Cardio Histopathology in L-NAME Intoxicated Experimental Rats

Coriandrum sativum has been used in traditional medicines as an anti-inflammatory, analgesic, and antibacterial agent. It is recently been shown to have antioxidant activities. This study evaluated the effects of Flavonoid Rich Fraction of Coriandrum sativum Leaf (FRFCSL) on Lipid Profile, Nitric Oxide, Ang II and Cardio Histopathology in L-NAME intoxicated Experimental Rats. Standard analytical method and DPPH radical scavenging activity were employed for the phytochemicals and antioxidant analysis respectively. The acute toxicity study showed the extract and flavonoids fraction are nontoxic at 5000mg/kg body weight. Thirty rats were divided into five groups of six (6) rats each. Group 1 was administered water and feed only, Group 2 was administered 40mg/kg N-Nitro-L-Arginine Methyl Ester (L-NAME) without treatment, Group 3 through 5 were administered 40mg/kg N-Nitro-L-Arginine Methyl Ester (L-NAME) with concomitant administration of Captopril (20mg/kg b.w), FRFCSL (200mg/kg b.w) and FRFCSL (400mg/kg b.w) respectively for 21 days. In phytochemical screening, presence of flavonoids, saponins, tannins, alkaloids, cardiac glycosides, steroids were confirmed as part of secondary metabolites in the extract. The flavonoid fraction showed increase % DPPH radical inhibition in concentration-dependent manner. FRFCSL treatment significantly (p&lt;0.05) and dose-dependently lowered low density lipoprotein and triglycerides. Also It significantly (p&lt;0.05) prevented L-NAME induced decrease in serum angiotensin II, high density lipoprotein and serum nitric oxide concentrations compared to the untreated rats. The Flavonoid Rich Fraction of Coriandrum Sativum Leaf showed great potential as antihypertensive, antihyperlipidemic and cardioprotective agent in rats thus confirming its usefulness in traditional health therapy and potential for antihypertensive drug development.

The Effects of Chrysanthemum morifolium Flower Extract on Obesity-Induced Inflammation and Muscle AMPK/SIRT1 Activities in Obese Rats

ObjectivesThe objective of this study is to investigate the effects of hot water extract of Chrysanthemum morifolium Ramat flower (CE) on obesity-induced inflammation and skeletal muscle mitochondrial function in high-fat diet fed rats. MethodsMale Sprague-Dawley rats (3-week-old) were randomly divided into 4 groups, and fed with a normal diet (NOR), high fat diet (HF), HF containing 0.2% CE (CEL) or 0.4% CE (CEH) for 13 weeks. ResultsCE reduced body weight and total white adipose tissue weights. The levels of serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) significantly reduced in the CEL and CEH groups compared to the HF group. In white adipose tissue, CE attenuated HF-induced adipose tissue macrophage (ATM) infiltration and down-regulated F4/80 mRNA expression compared to the HF group. In addition, CE down-regulated the mRNA levels involved in inflammation and ATM polarization, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattracted protein-1 (MCP1), inducible nitric oxide synthase (iNOS), and cluster of differentiation 11c (CD11c) compared to the HF group. On the other hand, gene expression of arginase 1 (Arg1), a M2 macrophage marker was significantly up-regulated in the CEL and CEH groups compared to the HF group. Nuclear factor-kappa B (NF-κB) activities and serum nitric oxide (NO) concentrations were significantly decreased by CE supplementation. In skeletal muscle, mitochondrial size and mitochondrial DNA (mtDNA) content were significantly increased in the CEL and CEH groups compared to the HF group. CE supplementation were also up-regulated the mRNA expression related to mitochondrial function, including sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), and carnitine palmitoyltransferase 1β (CPT-1β). Furthermore, activities of AMP-activated protein kinase (AMPK) and SIRT1 were increased by CE supplementation. ConclusionsThese results suggested that CE attenuates obesity-induced inflammation via regulating M1/M2 macrophage and increases the muscle mitochondria content and AMPK/SIRT1 activities. Funding SourcesThis research was supported by the BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF).

MO282: Sigma-1 Receptor Agonists are Protective in Renal Ischemia/Reperfusion Injury

Abstract BACKGROUND AND AIMS Renal ischemia/reperfusion injury (IRI)-induced acute kidney injury is associated with high mortality and morbidity and effective therapies are lacking. We previously showed that Sigma-1 receptor (S1R) agonist fluvoxamine treatment is protective against renal IRI (Hosszu et al, 2017). Here in a rat model, we studied the renoprotective effect of specific, high affinity S1R agonists focusing on the S1R-Akt-eNOS signaling pathway and renal vasoregulation. METHOD 8-week old male Wistar rats (n = 8/group) were subjected to 50 min unilateral ischemia with contralateral nephrectomy, kidney tissue was harvested 24 h after reperfusion. 30 min prior to the ischemic insult rats were treated i.p. as follows: (i) isotonic saline as vehicle; (ii) highly specific, high affinity S1R agonist SA-4503; or (iii) SA-4503 + S1R antagonist NE100. Sham-operated rats were used as controls. Renal functional parameters (BUN, serum creatinine, serum aspartate aminotransferase, kidney injury molecule 1 (Kim1), neutrophil gelatinase-associated lipocalin (Ngal) were evaluated. Structural damage was assessed on PAS-stained kidney sections. Renal S1R, phospho-Akt and phospho-eNOS, Hif-1α protein levels and serum nitric oxide (NO) concentration were measured. In vitro experiments were performed on HK2 human proximal tubular epithelial cells treated with a 10 µM dose of S1R agonist SA-4503 or PRE-084. RESULTS Impaired kidney function and structural damage after I/R were ameliorated by SA-4503. Expressions of early and sensitive tubular injury markers Kim1 and Ngal were markedly less elevated in SA-4503-treated rats. This recovery was blocked with the addition of the S1R antagonist NE100. S1R, phospho-Akt and phospho-eNOS protein levels were significantly elevated in the kidneys of SA-4503 treated rats. Vasodilator nitric oxide concentration was reduced in the kidney after IRI, but returned to control levels in SA-4503-treated rats. Treatment with S1R agonists SA-4503 and PRE-084 increased the NO production of HK-2 cells. CONCLUSION The specific and high affinity S1R agonist SA-4503 acts directly on proximal tubular cells by activating the S1R-NOS system. Thereby SA-4503 is renoprotective by increasing vasodilative NO production and thus improving post-ischemic renal perfusion. Based on our data activation of S1R and downstream signaling pathways could provide a novel therapeutic option in renal IRI. Founding OTKA PD-131 637; FK-124 491; 2020–4.1.1.-TKP2020-6 183 069 269; 2020–4.1.1.-TKP2020-6 183 169 273; KDP-2020/1 019 145