nitric oxide

Endothelial dysfunction is a consequence of obesity and metabolic syndrome. In this study, the effect of CX Works training (CX) on serum endothelial microparticles (EMPs) and nitric oxide (NO) as markers of vascular endothelial function was measured in women with metabolic syndrome.

For this purpose, 24 sedentary adult obese women were randomly divided into CX (8 weeks, n= 12) and control (no training, n = 12) groups. CX were performed every other day for 8 weeks. Serum NO and EMPs after an overnight fast were measured in both study groups (pre-training) and measurements were repeated 48 hours after the last CX training session (post-training). Independent / paired t-test was used to compare between groups.

CX training resulted in significant increase in serum NO and decrease in EMPs compared to the pre-training (p<0.05). No significant change were observed in any variables in control groups (p>0.05).

CX training, as a novel exercise modality, is associated with improved vascular endothelial function in women with metabolic syndrome. Measurement of other vascular markers is needed to better understand the mechanisms responsible for these changes.

Numerous factors contribute to the advancement of progressive kidney damage in chronic kidney disease (CKD). Among these, oxidative damage plays a significant role in the progression of CKD. The reactions involving free radicals are recognized as a crucial element that can exacerbate oxidative damage in patients with CKD. However, the precise mechanisms underlying oxidative damage remain incompletely understood. Consequently, this study aimed to explore oxidative and other associated biochemical parameters.

This case-control study included 38 male and 23 female patients, with mean ages of 58.9 ± 15.9 and 62.13 ± 13.43 years, respectively. At the same time, 40 healthy male and 22 healthy female individuals with an average age of 60.33 ± 10.62 and 59.3 ± 6.64, respectively, were selected as the control group who had no history of any diseases such as hypertension, diabetes, infection and kidney disease. Research variables including malondialdehyde (MDA), nitric oxide metabolites (nitrite/nitrate), and homocysteine (Hcy) concentration were measured in both case and control groups. Statistical analysis was done according to the obtained results.

There was a significant increase in homocysteine concentration in CKD patients compared to the control (P = 0.001). Nitrite and nitrate metabolites exhibited a substantial reduction in patients when compared to the control group (P = 0.001). On the other hand, malondialdehyde (MDA) showed a significant increase in patients compared to controls (P = 0.01).

The findings indicate that homocysteine levels, lipid peroxidation, and alterations in nitric oxide may significantly contribute to the progression of oxidative damage in patients with chronic kidney disease (CKD) and may also influence the disease’s pathogenesis.

  Polycystic ovary syndrome (PCOS) casts a wide shadow over the reproductive health of millions of women worldwide, emerging as one of the most complex and multifaceted endocrine disorders. In addition, nitric oxide (NO) stands out as a pivotal signaling molecule, orchestrating a symphony of physiological processes.

This meta-analysis aims to elucidate the association between NO levels and PCOS, investigate the potential of NO as a biomarker for PCOS diagnosis, and evaluate its clinical significance.

A systematic review was conducted in several electronic databases, including PubMed, Web of Science, Cochrane Library, Scopus, EMBASE, and Google Scholar, to identify relevant studies published up to January 2024. Standardized mean difference and 95% CI were calculated using a random effects model to assess the overall effect size. Meta-regressions and subgroup analysis were performed to investigate sources of heterogeneity.

A meta-analysis of 14 studies with 1171 participants showed that NO levels were significantly lower in the PCOS group than in the control group. The pooled analysis yielded a standardized mean difference of -0.482; 95% CI: -0.908 to -0.056; p = 0.027. Subgroup analyses further demonstrated variations in NO levels between different PCOS phenotypes and in relation to metabolic parameters.

This meta-analysis provides evidence for an association between PCOS and dysregulated NO levels and suggests a potential role of NO as a biomarker in the diagnosis and pathogenesis of PCOS.

Evidence?based screening is crucial to detect myocardial ischemia in high?risk diabetics. We explored the relationship between nitric oxide (NO) levels, lipid profile indices, and atherogenic index of plasma (AIP) in type 2 diabetics with coronary artery disease (CAD) and to determine their potential as prognostic markers.

A case–control study included 50 diabetics with CAD (cases), 30 diabetics without CAD (control 1), and 23 healthy controls (control 2). Biochemical parameters were determined using standard protocols; plasma NO was measured via the Griess reaction.

Cases had the highest levels of NO, fasting blood sugar, glycated hemoglobin (HbA1c), and triglycerides, and the lowest total cholesterol (TC), high?density lipoprotein cholesterol (HDL?C), and low?density lipoprotein cholesterol (LDL?C) levels. Cases exhibited the highest TC: HDL?C, LDL?C: HDL?C, and AIP ratios. A significant positive correlation between NO and HbA1c (r = 0.328, P = 0.020).

Chronic hyperglycemia could enhance NO overproduction driven by inducible isoform, suggesting a potential role for chronic hyperglycemia in endothelial dysfunction and vascular complications in diabetes.

Demyelination and inflammation are the most common pathobiological manifestations contributing to depression in multiple sclerosis (MS).

The current study aimed to evaluate the effects of acetyl-L-carnitine (ALC) in attenuating depressive-like symptoms in the cuprizone intoxication mouse model.

C57BL/6 mice were categorized into three groups (n = 6 each) as follows: The control animals (CTL), the cuprizone-intoxicated mice (CPZ), and the group that received cuprizone and acetyl-L-carnitine (CPZ+ALC). Depressive-like behaviors were evaluated by the forced swim test (FST) and the tail suspension test (TST). The prefrontal cortex (PFC) and corpus callosum (CC) areas were assessed in terms of histopathology, biochemistry, and gene expression.

Following oral gavage of ALC, the immobility time, which represents the despairing time, significantly decreased compared to the CPZ group. Histopathological evaluation showed that remyelination in the CC increased significantly in animals receiving ALC compared to the CPZ mice. Acetyl-L-carnitine considerably decreased the nitric oxide (NO) level in the PFC of the brain in the demyelinated mice compared to the CPZ group. The qRT-PCR results revealed that ALC significantly increased neuronal nitric oxide synthase (nNOS) expression but decreased inducible nitric oxide synthase (iNOS) gene expression compared to the CPZ group.

Acetyl-L-carnitine attenuated depressive-like behaviors in the cuprizone demyelination mouse model of MS. These neuroprotective effects of ALC may be exerted by facilitating the remyelination process and modulating the NO level in the PFC.

Paraxanthine is the major metabolite of caffeine in humans. There is no definitive proof that paraxanthine affects seizures. Nitric oxide (NO) contributes to the central effects of paraxanthine.

In this study, we examined the effect of acute paraxanthine administration on the pentylenetetrazole (PTZ)-induced seizure threshold, focusing on the NO-cyclic guanosine monophosphate (cGMP) signaling pathway.

Naval Medical Research Institute (NMRI) male mice (25 - 30 g) received paraxanthine (5, 10, 50, and 100 mg/kg) alone. L-arginine [a substrate for NO synthase (NOS)] (50 mg/kg) or L-NAME [a non-selective NOS inhibitor] (5 mg/kg) was administered alone or as pretreatment before the ineffective or effective doses of paraxanthine, respectively. The intravenous PTZ seizure threshold test was used to determine the thresholds for the onset of myoclonic twitch (MCT), generalized clonus (GNC), and forelimb tonus (FLT). Nitric oxide metabolites (NOx) were measured using the Griess method.

Paraxanthine administered at doses of 10 and 50 mg/kg significantly reduced the threshold for FLT (P < 0.05 for both). At a dose of 100 mg/kg, paraxanthine significantly reduced the thresholds for the onset of MCT (P < 0.001), GNC (P < 0.01), and FLT (P < 0.001). L-arginine (50 mg/kg), either alone or as pretreatment before paraxanthine (5 mg/kg), did not significantly change the seizure threshold. L-NAME (5 mg/kg) alone had no effect, but L-NAME pretreatment before paraxanthine (100 mg/kg) significantly increased the thresholds for the onset of MCT (P < 0.001), GNC (P < 0.001), and FLT (P < 0.001). Only paraxanthine at a dose of 100 mg/kg significantly increased NOx levels in brain tissues (P < 0.05). Pretreatment with L-arginine further increased the NOx level (P < 0.001), whereas pretreatment with L-NAME decreased it (P < 0.001) compared to the paraxanthine groups.

Our results show that paraxanthine has a proconvulsant effect. The results of L-arginine or L-NAME pretreatment before paraxanthine support the possible interaction of the NO-cGMP pathway in the proconvulsant effect of paraxanthine.

Type 2 diabetes is the most common type of diabetes characterized by insulin resistance and beta cell dysfunction. The speed of wound healing is very important in the healing process. Research shows that the use of natural products and traditional medicine methods in treating many diseases and wounds has spread worldwide. Therefore, the present study aims to investigate the histopathological effectiveness of Pistacia atlantica extract (Beneh) in improving the experimental model of diabetic wounds. 

This study was conducted on 48 BALB/c mice. To induce type 2 diabetes, the animals received a high-fat diet for two weeks, and then a single dose of 30 mg/kg was injected intraperitoneally. The wound was created by an excisional wound splinting model and biopsy punch. Glucose level was measured with a glucometer, and insulin level was measured using an ELISA kit. Histopathological examination was also done using hematoxylin/eosin staining and Masson trichrome staining.

The macroscopic study showed that the wound size was reduced in both P. atlantica extract and silver sulfadiazine groups compared to the wound control group. The results of hematoxylin and eosin staining also showed a reduction in inflammation in the wound area in the treatment groups. The re-epithelialization occurred well in both treatment groups. However, its speed was higher in the P. atlantica-treated group than in the silver sulfadiazine group. Masson’s trichrome staining results showed the collagen fibers in the P. atlantica group have a more regular arrangement than silver and wound control groups. The results of the serum analysis also showed that the gum extract of P. atlantica reduced the production of NO and MPO in the treatment groups compared to the control group.

The results of our study showed that the use of P. atlantica extract topically in the diabetic wound area can improve the rate of closure and re-epithelialization in the diabetic wound by reducing inflammation.

The nitrate-nitrite-nitric oxide (NO) is considered a possible alternative pathway for NO production. Consequently, this research aimed to assess how adding dietary nitrate or nitrite affects the inhibitory avoidance task, the threshold for clonic seizures induced by pentylenetetrazole (PTZ), and levels of nitric oxide metabolites (NOx) in mice.

In this research, 40 male NMRI mice were used, with 8 mice in each of the five groups including control and four experimental groups (given 50 or 100 mg/l nitrate or nitrite in drinking water for 21 days). The mice’s memory retention was assessed through the step-down passive avoidance test, while their locomotor activity was measured using the open-field apparatus. The seizure threshold was determined by administering PTZ through intravenous infusion. Additionally, the levels of NOx in the brain tissue were quantified using the Griess method.

Supplementation with either nitrate or nitrite at a concentration of 100 mg/L resulted in a significant increase in the step-down passive avoidance latency compared to the control group (P<0.01). Only nitrate at a concentration of 100 mg/L significantly increased the threshold for PTZ-induced clonic seizures (P<0.001). The levels of NOx were significantly elevated in all groups that received nitrate or nitrite at concentrations of 50 and 100 mg/L (P<0.05).

We conclude that the nitrate-nitrite-NO pathway is partly involved in the memory-improving effects of nitrate or nitrite and the increase of PTZ-induced clonic seizure threshold following nitrate supplementation.

Statins affect the bone metabolism. Considering the role of nitric oxide (NO) in many physiological processes, this study assessed the effects of atorvastatin (ATOR) and NO on the mandible and skull bone density (BD) in ovariectomized rats. This study evaluated 48 female Sprague-Dawley rats in 6 groups (n=8). Groups 1 and 2 underwent sham surgery. Group 1 (sham) did not receive any medication, but group 2 (sham/ATOR) received atorvastatin. Groups 3 to 6 underwent ovariectomy. Group 3 (OVX) did not receive any medication, group 4 (OVX/ATOR) received atorvastatin, group 5 (OVX/L-NAME) received L-NG-nitro arginine methyl ester (L-NAME), and group 6 (OVX/ATOR/L-NAME) received both atorvastatin and L-NAME. Atorvastatin (40 mg/kg) was gavaged and L-NAME (3 mg/kg) was administered intraperitoneally for 4 weeks. All rats underwent lateral cephalometry before and after the interventions, and BD was measured at 2 points in the mandible and skull before and after the intervention by a digital densitometer. Data were analyzed by t-test, ANOVA, and Sidak test (alpha=0.05). The change in BD was 26.5±10.17 in the mandible and 22.17±9.45 in the skull in OVX group. These values were 25.63±5.55 and 28±8.59 in OVX/ATR, 1.5±7.78 and -1.88±4.39 in OVX/L-NAME, and 6.63±7.37 and 4.33±6.35 in OVX/ATOR/L-NAME, respectively. OVX/ATOR showed no significant difference (P=1), but OVX/L-NAME (P<0.001) and OVX/ATOR/L-NAME (P<0.001) groups showed significant differences with OVX group. The present findings indicated that atorvastatin had no significant effect on BD, but administration of L-NAME prevented osteoporosis in ovariectomized rats.

Although exogenous nitric oxide (NO) is used as medicine, in the previous we showed its inhibitory effect on the proliferation ability of rat bone marrow mesenchymal stem cells (BMSCs). In the present investigation, the inhibitory role of exogenous NO on BMSCs cell cycle was studied.

BMSCs after the third passage were treated for one hour every 48 hours with 100μM of sodium nitroprusside as an NO donor. Then, after 5,10,15, and 20 days of treatment, the viability, proliferation, and cell cycle of the BMSCs was investigated. In addition, the expression of the Raf1, CDK2, CDK4, P53, and GAPDH genes was studied.

Cell treatment caused a significant reduction in viability and proliferation at 5,10,15, and 20 days. Also, the treatment caused cell cycle arrest at G1 after 20 days. In addition, it was found that the CDK2 and CDK4 expression were down-regulated whereas the P53 expression was up-regulated, but the expression of Raf1 as well as GAPDH remained the same.

This study showed that prolonged treatment with a NO donor arrest the BMSCs cell cycle due to overexpression of P53, which inhibits the expression of Cdk2 and Cdk4.

The study investigates the effects of four different doses of computed tomography (CT) x-ray radiation on the oxidation markers, endogenous antioxidant enzymes, and lipid profiles of male Wistar albino rats. Thirty healthy male Wistar albino rats weighing 180-200g were assigned into five groups of 6 rats each. Rats in groups A, B, C, and D underwent non-contrast helical total body irradiation and received varying doses of CT radiation, while group E received sham irradiation and served as a control. Glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT) activities, serum levels of malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were investigated using standard methods. At 72 hours’ post-irradiation, the mean serum activities of GPx, SOD, and CAT in the irradiated groups decreased significantly, while the serum levels of MDA, GSSG, TC, and LDL increased significantly compared to the control. The four different doses of CT radiation in the current study caused a significant decline in the endogenous antioxidant enzymes (GPx, SOD, and CAT) and, in contrast, induced a significant serum elevation of MDA and GSSG in the irradiated rats. The LDC and TC mean serum levels were also significantly elevated in the irradiated groups.

Evaluating the effect of fresh Oleaster leaf extract (OLE) and purified oleuropein (OLR) on ethanol-induced gastric ulcers in rats. HPLC analysis demonstrates the presence of various polyphenol compounds such as ligstroside, luteolin derivative, oleuropein, and comselogoside. 

Gastric ulcer was induced by administration of ethanol by the gastric gavage route. The olive leaf extract was analyzed by HPLC-PDA-ESI-MS, and OLR was purified. These two compounds were given 2 hr before gastric ulcer induction by ethanol.

This study verified that OLE and purified OLR protect from ethanol-induced gastric ulceration and damage, evidenced by the significant decrease in gastric ulcer urea (by 74 and 58% respectively) and stomach mucus content (by 169 and 87% respectively). In addition, the ulcer index (UI) and curative index (CI) levels in the stomach of the rats treated with this supplement were also suppressed by 55 and 46%, respectively. OLE and OLR also decreased the gastric myeloperoxidase (MPO) activity and ameliorated the Nitric oxide (NO) content. OLE and OL also ingestion suppressed gastric tumor necrosis factor-alpha (TNF-α) and interleukin (IL-6) rates. Macroscopic and histological findings revealed that OLE and OLR protect from gastric hemorrhage, severe disruption of the gastric mucosa, and neutrophil infiltration.

Overall, the findings demonstrate that OLE and OLR have both promising potential with regard to the inhibition of gastric hemorrhage and lesions.

We aimed to investigate the cytotoxic and apoptotic effects of miltefosine on Toxoplasma gondii RH strain by various techniques.

The study was conducted at the Department of Parasitology and Mycology, Urmia University of Medical Sciences, Iran in 2020. Four groups of five BALB/c mice were selected. The cytotoxicity test was conducted by adding miltefosine to T. gondii tachyzoites; control tachyzoites received PBS and MTT assay was done on each suspension. For evaluating the Th1-type immune responses, the serum levels of IFN-γ and nitric oxide (NO) were assessed in mice after injecting tachyzoites and miltefosine, respectively. The flow cytometry technique was performed on T. gondii tachyzoites challenged with IC50 and IC90 doses of miltefosine and unchallenged cells. DNA fragments in T. gondii tachyzoites were detected by Terminal dUTPnick-end labeling (TUNEL) method.

Overall, 256, 64, 32, and 16 µg concentrations of miltefosine, respectively could kill more than 50% of viable T. gondii tachyzoites. The infected mice group, treated with miltefosine, significantly produced more IFN-γ relative to other groups (P< 0.001). Moreover, a significant difference was found in inducible NO synthase between the experimental and control groups (P<0.05). The flow cytometry results demonstrated a concentration-dependent apoptosis rate in tachyzoites incubated with miltefosine, though the necrosis rate was non-significant. DNA fragmentation analysis indicated oligonucleotides (18-200 bp) in tachyzoites treated with 11µg of miltefosine for 24, 48 and 72 h. However, this pattern was not observed in untreated control microorganisms.

Miltefosine could be a favorable candidate for use as a new treatment for toxoplasmosis.

We aimed to track longitudinal changes of glycemic status in subjects with prediabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years.

This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio.

Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (Ptime×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018).

A higher endogenous NO production (i.e., indirectly measured by BW- and Cradjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.