Relationship between synovial fluid and plasma manganese,arginase, and nitric oxide in patients with rheumatoid arthritis

Nitric oxide (NO) participates in the pathogenesis of inflammatory reactions in many autoimmune diseases such as rheumatoid arthritis (RA). There is a reciprocal pathway between arginase and nitric oxide synthese (NOS) for NO production, and Mn is required for arginase activity and stability. To investigate whether NO production related with the arginine-nitric oxide pathway in patients with RA, we measured synovial fluid and plasma nitrite (NO_x) levels, arginase activities, and its cofactor manganese (Mn) concentrations in 21 RA patients and 13 healthy control subjects. Plasma albumin levels were measured as an index of nutritional status. NO_x levels were determined after the reduction of nitrates to nitrites using the Griess reaction. Whereas, synovial fluid arginase activities and Mn levels were found to be significantly lower (p<0.001, p<0.001, respectively), plasma arginase activities and Mn levels were similar in patients with RA when compared to the control subjects. Plasma and synovial fluid NO levels were similar in patients with RA and in healthy subjects (p>0.05, p>0.05, respectively). There were significantly positive correlations between synovial fluid and plasma arginase activities vs Mn content (r=0.543, p=0.011; r=0.516, p=0.017, respectively) and significantly negative correlations between synovial fluid and plasma NO levels vs arginase activities (r=−0.497, p=0.022; r=−0.508, p=0.019 respectively) in the patients group. Our results indicate that the lower concentration of synovial fluid Mn could cause lower arginase activity and this could also upregulate NO production by increasing L-arginine content in patients with RA.     

Relationship among levels of leptin and zinc,copper, and zinc/copper ratio in plasma of patients with essential hypertension and healthy normotensive subjects

Obesity is among the main contributing factors in the etiology of essential hypertension (EHT). Leptin, the product of the ob gene, is expressed mainly in adipose tissue. We examined the relationship between two trace elements, zinc (Zn) and copper (Cu), and leptin in patients with EHT (n=35) and normotensive (NT) controls (n=50) because leptin as well as Zn and Cu were reported to be associated with the pathophysiology of EHT. Plasma leptin levels were determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Atomic absorption spectrophotometry was utilized to determine plasma Zn and Cu levels. There was a negative correlation between leptin and Zn, and the Zn/Cu ratio (r=−0.359, p<0.05; r=0.361, p<0.05, respectively) in pooled subjects. When subjects were divided based on the presence or absence of hypertension, there was a negative correlation between leptin and Zn (r=−0.375, p<0.05) as well as leptin and Zn/Cu ratio (r=−0.398, p<0.05) in NT subjects. Similar trends were observed when leptin/BMI (body mass index) levels were utilized. There was no significant correlations between levels of Cu and leptin or leptin/BMI. In conclusion, in addition to high leptin levels, Zn and the Zn/Cu ratio were lower in patients with EHT compared to NT controls.     

Trace element and magnesium levels and superoxide dismutase activity in rheumatoid arthritis

It has been suggested that reactive oxygen metabolites and trace elements play some role in the etiology and pathogenesis of rheumatoid arthritis (RA). Superoxide dismutase (SOD) is believed to exert an important protective role against oxygen toxicity. The aim of the study was to investigate the probable changes in the levels of trace elements and SOD activity in RA. Plasma and erythrocyte copper, zinc, and magnesium levels and erythrocyte SOD activity were measured in groups of controls and RA cases. Significantly increased erythrocyte SOD activity was found in RA patients in comparison with controls(p < 0.0001). A rise in erythrocyte Zn level(p < 0.0001) and plasma Cu level(p < 0.0001) and a decrease in erythrocyte Cu level(p < 0.05) and plasma Zn level(p < 0.05) were obtained in RA patients when compared to controls. Plasma and erythrocyte Mg levels of the RA patients showed slight and statistically insignificant reductions when compared to controls(p > 0.05). In RA patients, there were positive correlations between erythrocyte SOD activity and Mg level (r = 0.4345,p < 0.01) and between erythrocyte Zn level and plasma Cu level(r = 0.4132,p < 0.01). There were negative correlations between erythrocyte SOD activity and plasma Zn level(r =-0.3605,p < 0.05) and between plasma Zn level and erythrocyte Cu level(r =-0.4578,p < 0.01) in RA patients. This work was presented at the International Congress on Free Radicals in Health and Disease, 6–10 September 1995, Istanbul, Turkey.     

Plasma selenium levels in rheumatoid arthritis

The plasma selenium (Se) levels were determined in patients with rheumatoid arthritis (RA) and healthy controls. Plasma Se levels in 60 patients were found to be significantly lower than those in 60 normal, healthy controls (p<0.001). Similar significant differences were determined in sex-matched comparisons between patients and controls (p<0.001) but there was no significant difference in plasma Se levels in sex-matched comparisons in both groups (p>0.05). Our results suggest that Se is an important factor in RA.     

Alterations in plasma essential trace elements selenium, manganese, zinc, copper, and iron concentrations and the possible role of these elements on oxidative status in patients with childhood asthma

The aim of the present study is to evaluate the status of plasma essential trace element selenium (Se), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) concentrations and the effect of these elements on oxidative status in patients with childhood asthma. Plasma Se, Mn, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry (AAS) and Fe concentrations, malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined by the colorimetric method. The plasma MDA/TAC ratio was calculated as an index of oxidative status. Plasma albumin levels were measured to determine nutritional status. Plasma Fe concentrations, MDA levels and the MDA/TAC ratio were significantly higher (p<0.001, p<0.001, and p<0.01, respectively) and Se and Mn concentrations and TAC were lower (p<0.01, p<0.05, and p<0.01, respectively) in patients when compared to the healthy subjects. Plasma Zn, Cu, and albumin levels were not found to be significantly different in patients and controls (p>0.05). There were positive relationships between plasma MDA and Fe (r=0.545, p<0.001) and TAC and Se (r=0.485, p<0.021), and a negative correlation between TAC and MDA values (r= −0.337, p<0.031) in patients with childhood asthma. However, there was no correlation between these trace elements and albumin content in patient groups. These observations suggest that increased Fe and decreased Se concentrations in patients with childhood asthma may be responsible for the oxidant/antioxidant imbalance.     

A case-control study on selenium,zinc, and copper in plasma and hair of subjects affected by breast and lung cancer

The purpose of our study was to investigate the relationship between plasma and hair levels of Se, Zn, and Cu, and cancer. We selected a total of 66 patients affected by either breast (38) or lung (28) cancer. They entered into the study at the onset of disease, and before any chemical or radiotherapy. Controls were randomly selected among healthy people and were matched for sex, age, smoking habits, and residence. In the group of breast cancer, a significant decrease in hair Se was found compared to controls (p<0.01), whereas plasma Se was only slightly decreased. No difference between cases and controls was detected in both hair and plasma levels of Zn and Cu. Subjects who developed lung cancer were significantly lower in hair Zn (p<0.05) and Cu (p<0.01) than controls, whereas there was no difference with regard to Se. In addition, plasma Cu of these patients was increased as compared to controls.     

The levels of some antioxidant vitamins,glutathione peroxidase and lipoperoxidase during the anaesthesia of dogs

The aim of this investigation was to determine serum levels of vitamin A, E, beta carotene, glutathione peroxidase (GSHPx), lipid peroxidation (MDA) and biochemical and haematological parameters during enflurane anaesthetised dogs. Ten kangal dogs were used and all animals were anaesthetised with enflurane for two hours and blood samples were taken before and 30, 120 minutes, 24 hours and 7 days during the anaesthesia. Vitamin E and beta carotene content were significantly (p<0·05 and p<0·01) higher before anaesthesia than after whereas serum GSHPx activity was not statistically different. However, serum levels of vitamin A and MDA were significantly (p<0·05) increased during the anaesthesia. In general, serum levels of aspartate aminotransferase, alanine aminotransferase, albumin, glucose, urea and creatinine were significantly (p<0·05 and p<0·01) increased during anaesthesia and returned to near normal values after 7 days of anaesthesia, whereas the white blood cell count was significantly (p<0·05 and p<0·01) decreased during the anaesthesia. However, the red blood cell count, haemoglobin and packed cell volume values, and levels of total cholesterol, triglycerides, total protein and globulin were apparently not influenced by the anaesthesia. In conclusion, we observed that the serum level of vitamin E and beta carotene were significantly decreased, whereas serum MDA and vitamin A levels were significantly increased during the enflurane anaesthesia. Copyright © 1999 John Wiley & Sons, Ltd.     

Essential trace elements selenium, zinc, copper, and iron concentrations and their related acute-phase proteins in patients with vivax malaria

The aim of the present study is to evaluate the status of plasma essential trace elements selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) concentrations and their related acute-phase proteins, ceruloplasmin (Cp), ferritin, transferrin (Tf), and albumin levels in patients with vivax malaria. Plasma Cu and Zn concentrations were determined by atomic absorption spectrometry (AAS). Se concentrations were determined by graphite furnace AAS. Fe, Cp, Tf, and albumin levels were determined by colorimetric methods. Plasma Se, Fe, and albumin levels were found to be significantly lower (p<0.01, p<0.001, and p<0.05, respectively) and Cu, Cp, and ferritin levels and Cu/Zn ratios were significantly higher (p<0.001, p<0.001, p<0.001, and p<0.05, respectively) in patients when compared with those of healthy subjects. Plasma, Tf, and Zn levels were not found to be significantly different (p>0.05) in patients and controls. There were positive important correlations between Cu and Cp (r=0.908, p<0.001), Zn and albumin (r=0.633, p<0.001), and negative correlations between Fe and ferritin content (r=−0.521, p<0.05) and Fe and Tf (r=−0.616, p<0.01) in the patients group. Our findings demonstrated that plasma essential trace elements Se, Cu, and Fe change, but these changes might be dependent on acute-phase proteins, which were regulated as a part of defense strategies of the organism, induced by hormonelike substances.     

Effects of X-ray radiation on lipid peroxidation and antioxidant systems in rabbits treated with antioxidant compounds

The aim of this study was to investigate the effects of supplemental antioxidant vitamins and minerals on lipid peroxidation and on the antioxidant systems in rabbits exposed to X-rays. The rabbits were divided into two experimental groups and one control group, each group containing seven rabbits. The first group (VG) received daily oral doses of vitamin E (460 mg/kg live weight) and vitamin C (100 mg/kg live weight). The second group (MG) was fed a mineral-enriched diet that contained 60 mg manganese chloride, 40 mg zinc sulfate, and 5 mg copper sulfate per kilogram of feed. The third group served as controls and received only a standard diet. Blood samples were obtained before and after the supplementation with vitamins or minerals, as well as before and after irradiation with a total dose of 550-rad X-rays. The blood samples were analyzed for their content of malondialdehyde (MDA), plasma vitamins C and E, retinol, reduced glutathione (GSH), and glutathione peroxidase activity (GPx). After irradiation, the control group showed increased levels of MDA and activity of GPx (p<0.05), whereas the levels of GSH, vitamin C, and vitamin E were decreased. In the VG, the concentration of MDA was lower (p<0.05), and the concentration of GSH and vitamins C and E were higher (p<0.05) when compared to controls. In the MG, the concentrations of MDA, GSH, vitamin C, and retinol were not affected by the mineral administration and radiation. The level of vitamin E in the MG increased with mineral administration (p<0.05), but decreased after irradiation (p<0.05). For the control group, the level of GSH was higher than in the two experimental groups. After irradiation, the VG animals had vitamin E and C levels that were higher than in MG and control groups (p<0.05). The activity of GPx was not affected by vitamin or mineral supplementation or by irradiation. We conclude that the supplementation with antioxidant vitamins and minerals may serve to reinforce the antioxidant systems, thus having a protective effect against cell damage by X-rays.     

Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteoarthritis

In recent years, a great number of studies have investigated the possible role of trace elements in the etiology and pathogenesis of rheumatoid arthritis (RA) and osteoartritis (OA). We studied synovial fluid and plasma concentrations of selenium (Se), zinc (Zn), copper (Cu), and iron (Fe) in patients with RA and OA and compared them with sex- and age-matched healthy subjects. Plasma albumin levels were measured as an index of nutritional status. Plasma Se, Cu, and Zn concentrations were determined by atomic absorption spectrophotometry and Fe concentrations were determined by the colorimetric method. Although plasma and synovial fluid Se concentration were found to be significantly lower (p<0.05, and p<0.05, respectively), Cu concentrations were significantly higher in patients with RA than those of healthy subjects and OA (p<0.05 and p<0.05, respectively). There were no significant differences in plasma and synovial fluid Zn concentrations and albumin levels among three groups (p>0.05). On the other hand, synovial fluid Cu and Fe concentrations were significantly higher in patients with OA than those of healthy subjects (p<0.05). There was a significantly positive correlation between synovial fluid Se−Cu values and Zn−Fe values in patients with RA. Our results showed that synovial fluid and plasma trace element concentrations, excluding Zn, change in inflammatory RA, but not in OA. These alterations in trace element concentrations in inflammatory Ra might be a result on the changes of the immunoregulatory cytokines.     

Serum lipid profile paraoxonase and arylesterase activities in psoriasis

Psoriasis is a common chronic and recurrent inflammatory skin disease with unknown etiology that has been associated with abnormal plasma lipid metabolism and oxidative stress. There are controversial results in the previous studies investigating oxidant/antioxidant systems in psoriasis. The aim of this work was to evaluate dyslipidemia, oxidative stress, total antioxidant capacity and serum paraoxonase (PON1) and arylesterase (ARE) activities in psoriasis, and to look for a correlation between these parameters and lesion percentage in psoriasis. Thirty psoriatic patients and twenty three sex‐ and agematched healthy volunteers were included in the study. From blood samples, lipid profile, malondialdehyde (MDA) levels, total antioxidant capacity (TAO), serum PON1 and ARE activities were determined. No significant differences between the patients and controls were found in terms of total cholesterol, triacylglycerol (TAG), HDL‐cholesterol, LDL‐cholesterol, VLDL‐cholesterol, MDA and TAO levels. Serum PON1 and sodium‐stimulated PON1 activities (p < 0.05) and ARE activity (p < 0.01) were found significantly higher in the patients than in the controls. There was not any significant correlation between lesion percentage and the parameters studied. Copyright © 2009 John Wiley & Sons, Ltd.     

New volatile anesthetic,desflurane, reduces vitamin E level in blood of operative patients via oxidative stress

It has been well known that some volatile anesthetic agents produce oxidative stress. Desflurane as a new volatile agent might have limited oxidative toxic effect because it is relatively a new short‐acting anesthetic characterized by a short duration of action and a quick postanesthetic recovery. We investigated effect of desflurane on serum glutathione peroxidase (GSH‐Px), lipid peroxidation (LP), vitamin E, and erythrocyte superoxide dismutase (SOD) values in patients. Fifteen adult patients are scheduled for elective surgery, ASA I or II physical status. Tidal volume and ventilation frequency were kept unchanged during the operation. Baseline values in venous blood samples were preoperatively taken and blood was also taken postoperatively at the 1st and the 12th hours of desflurane exposure. LP levels were significantly (p < 0.05) higher postoperatively at 1st hour than in preoperative values while α‐tocopherol concentration was significantly (p < 0.001) lower in postoperative period at 1st hour than in preoperative period. Erythrocyte SOD and serum GSH‐Px activities did not differ between pre‐ and postoperative periods. In conclusion, we observed that desflurane produced oxidative stress by decreasing α‐tocopherol levels. Use of vitamin E may be possible to reduce the oxidative effect of desflurane. Copyright © 2010 John Wiley & Sons, Ltd.     

Studies on biomarkers of copper exposure and toxicity in the marine amphipod Gammarus locusta (Crustacea): I. Induction of metallothionein and lipid peroxidation

Sublethal exposures of the marine amphipod Gammarus locusta to a concentration range of copper (Cu) in water (4 days' exposure; 3, 5 and 10 μg Cu l^-1) or spiked sediments (28 days' exposure; 1, 3 and 6 mg Cu kg^-1 dry weight) were performed, and the resulting bioaccumulation of Cu and effects on putative metallothionein (MT) and lipid peroxidation (LP) were investigated. A time-course exposure study (over 10 days) to a single water-borne concentration of Cu (4 μg l^-1) was also carried out. MT and LP were quantified, respectively, by differential pulse polarography and as thiobarbituric acid-reactive malondialdehyde equivalents. The increasing levels of Cu in water and sediment exposures resulted in enhanced uptake of the metal by G. locusta. Synthesis of putative MT occurred in response to exposure to water-borne Cu, the levels being higher (p < 0.05) over the dose range of Cu compared with controls. A positive correlation was observed between putative MT levels and the Cu body-burden concentration (p < 0.001). However, no increase in LP was observed in these animals. In contrast, in the time-course experiment, LP levels increased within 1 day of exposure, subsequently peaking at 4 days (68% greater than control, p < 0.001), before returning to control values by day 6. Higher levels of MT were also observed in this exposure, but at days 6 and 10 (55% and 38%, respectively), paralleling the decrease in LP. No increase in MT levels was recorded with exposure to Cu-contaminated sediments, whereas higher levels of LP were seen in comparison with controls (p < 0.001). Overall, the inverse relationship between putative MT induction and the occurrence of LP indicates that MT may protect against the prooxidant effects of Cu. It is concluded that MT and LP offer potential for application as biomarkers in G. locusta.     

Serum Myeloperoxidase Activity, Total Antioxidant Capacity and Nitric Oxide Levels in Patients with Chronic Otitis Media

It has been suggested that oxidative stress may play an important role in the pathogenesis of chronic otitis media (COM), but the role of oxidative stress in the pathogenesis of COM has not yet been fully explored. Therefore, the aim of this study was to investigate serum myeloperoxidase (MPO) activity, 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), total antioxidant capacity (TAC) and nitric oxide (NO) in patients with COM. Sixty-one patients with COM and 30 controls were enrolled in the present study. Patients were divided into two groups according to the presence (n = 21) or absence (n = 40) of cholesteatoma. Serum MPO activity and 4-HNE, MDA and NO levels were significantly higher in patients with COM than controls (for all, p < 0.001), while TAC levels were significantly lower (for all, p < 0.001). Serum MPO activity and MDA, 4-HNE and NO levels were significantly higher in patients with cholesteatoma than in those without cholesteatoma, while TAC levels were significantly lower; but the difference between groups was not statistically significant (p > 0.05). Increased oxidative stress seems to be associated with decreased antioxidant levels in patients with COM. Thus, increased oxidative stress may play a role in the pathogenesis of COM. It is believed that the administration of antioxidant vitamins such as A, C and E may be useful in preventing and treating COM.     

Concentrations of seven trace elements in different hematological matrices in patients with type 2 diabetes as compared to healthy controls

This study aimed to compare the trace element status of patients with type 2 diabetes (n=53) with those of nondiabetic healthy controls (n=50). The concentrations of seven trace elements were determined in the whole blood, blood plasma, erythrocytes, and lymphocytes of the study subjects. Vanadium and iron levels in lymphocytes were significantly higher in diabetic patients as compared to controls (p<0.05 for iron and p<0.01 for vanadium). In contrast, lower manganese (p<0.01) and selenium (p<0.01) concentrations were detected in lymphocytes derived from patients with type 2 diabetes versus healthy subjects. Furthermore, significantly lower chromium levels (p<0.05) were found in the plasma of diabetic individuals as compared to controls. Trace element concentrations were not dependent on the degree of glucose control as determined by correlation analysis between HBA_1c versus metal levels in the four blood fractions. In summary, this study primarily demonstrated that trace element levels in lymphocytes of patients with type 2 diabetes could deviate significantly from controls, whereas, in general, no considerable differences could be found when comparing the other fractions between both patient groups. Therefore, it seems reasonable to analyze metal levels in leukocytes to determine trace element status in patients with type 2 diabetes and perhaps in other diseases.     

Longitudinal study of serum zinc and copper levels in hemodialysis patients and their relation to biochemical markers

A 6-mo longitudinal study of 48 hemodialysis patients (HPs) with chronic renal failure was performed. Three blood samplings were done. Samples of whole blood from each patient were collected during hemodialysis sessions after passing through the artificial kidney. Zinc and copper levels were measured by atomic absorption spectrometry. Additionally, 36 biochemical indexes were evaluated during the study. Fifty-two healthy matched controls were also considered. Mean serum zinc and copper concentrations in HPs were significantly decreased (Zn) and increased (Cu), when compared with healthy controls (p<0.01). Zinc concentrations found in the first and second blood samplings from patients were significantly lower than those measured for the third sampling (p<0.01). The etiology of chronic renal failure influenced the statistically serum Zn levels of patients (p<0.05). Serum copper levels of HPs were significantly diminished by the existence of secondary associated diseases (p<0.01). Uric acid and parathyroid hormone, and total-cholesterol and glutamic-pyruvic-transaminase levels were significantly (p<0.05) and linearly related with serum zinc and copper concentrations, respectively. From all of indexes, creatinine, direct bilirubin, magnesium, calcium, parathyroid hormone, transferrin, and albumin were statistically modified along the longitudinal study (p<0.05). Transferrin serum levels were significantly diminished in the third blood sampling, indicating the tendency toward anemia in the patients. This result is reinforced by low levels of biochemical and hematological indexes related with iron body staus.     

Effect of Protein Intake on Bone Mineralization during Weight Loss: A 6‐Month Trial

Objective: The long‐term effect of dietary protein on bone mineralization is not well understood. Research Methods and Procedures: Sixty‐five overweight (body mass index, 25 to 29.9 kg/m²) or obese (≥30 kg/m²) subjects were enrolled in a randomized, placebo‐controlled, 6‐month dietary‐intervention study comparing two controlled ad libitum diets with matched fat contents: high protein (HP) or low protein (LP). Body composition was assessed by DXA. Results: In the HP group, dietary‐protein intake increased from 91.4 g/d to a 6‐month intervention mean of 107.8 g/d (p < 0.05) and decreased in the LP group from 91.1 g/d to 70.4 g/d (p < 0.05). Total weight loss after 6 months was 8.9 kg in the HP group, 5.1 kg in the LP group, and none in the control group. After 6 months, bone mineral content (BMC) had declined by 111 ± 13 g (4%) in the HP group and by 85 ± 13 g (3%) in the LP group (not significant). Loss of BMC was more positively correlated with loss of body fat mass (r = 0.83; p < 0.0001) than with loss of body weight. Six‐month BMC loss, adjusted for differences in fat loss, was greater in the LP group than in the HP group [difference in LP vs. HP, 44.8 g (95% confidence interval, 16 to 73.8 g); p < 0.05]. Independent of change in body weight and composition during the intervention, highprotein intake was associated with a diminished loss of BMC (p < 0.01). Discussion: Body‐fat loss was the major determinant of loss of BMC, and we found no adverse effects of 6 months of high‐protein intake on BMC.     

Short‐term interleukin‐37 treatment improves vascular endothelial function,endurance exercise capacity,and whole‐body glucose metabolism in old mice

Aging is associated with vascular endothelial dysfunction, reduced exercise tolerance, and impaired whole‐body glucose metabolism. Interleukin‐37 (IL‐37), an anti‐inflammatory cytokine of the interleukin‐1 family, exerts salutary physiological effects in young mice independent of its inflammation‐suppressing properties. Here, we assess the efficacy of IL‐37 treatment for improving physiological function in older age. Old mice (26–28 months) received daily intraperitoneal injections of recombinant human IL‐37 (recIL‐37; 1 µg/200 ml PBS) or vehicle (200 ml PBS) for 10–14 days. Vascular endothelial function (ex vivo carotid artery dilation to increasing doses of acetylcholine, ACh) was enhanced in recIL‐37 vs. vehicle‐treated mice via increased nitric oxide (NO) bioavailability (all p < .05); this effect was accompanied by enhanced ACh‐stimulated NO production and reduced levels of reactive oxygen species in endothelial cells cultured with plasma from IL‐37‐treated animals (p < .05 vs. vehicle plasma). RecIL‐37 treatment increased endurance exercise capacity by 2.4‐fold, which was accompanied by a 2.9‐fold increase in the phosphorylated AMP‐activated kinase (AMPK) to AMPK ratio (i.e., AMPK activation) in quadriceps muscle. RecIL‐37 treatment also improved whole‐body insulin sensitivity and glucose tolerance (p < .05 vs. vehicle). Improvements in physiological function occurred without significant changes in plasma, aortic, and skeletal muscle pro‐inflammatory proteins (under resting conditions), whereas pro‐/anti‐inflammatory IL‐6 was greater in recIL‐37‐treated animals. Plasma metabolomics analysis revealed that recIL‐37 treatment altered metabolites related to pathways involved in NO synthesis (e.g., increased L‐arginine and citrulline/arginine ratio) and fatty acid metabolism (e.g., increased pantothenol and free fatty acids). Our findings provide experimental support for IL‐37 therapy as a novel strategy to improve diverse physiological functions in old age.     

Influence of nitric oxide synthase inhibition on vasopressin and corticosterone secretion during water deprivation in rats

Nitric oxide (NO) is a short-lived radical that functions as a neurotransmitter in the central nervous system and plays a physiological role in the regulation of hypothalamic–pituitary–adrenal axis and vasopressinergic axis. In the present study, we aimed to investigate the interaction between the generation of NO and vasopressin (AVP) and corticosterone release after 3 days of water deprivation in rats. Animals were previously treated with intraperitoneal (i.p.) saline or l-nitro-arginine methyl ester (L-NAME) injection. l-NAME is a nonspecific inhibitor of nitric oxide synthases. In control rats given i.p. saline or l-NAME, hypothalamic, pituitary, and plasma AVP levels and plasma corticosterone did not change from baseline levels (p > 0.05). Three days of water deprivation increased significantly the corticosterone levels in plasma (p < 0.01) and AVP levels in hypothalamus and plasma (p < 0.01), but not in pituitary, which showed a significant decrease. These variations were concomitant with the elevation of nitrates/nitrates in plasma. l-NAME injection abolished significantly (p < 0.01) the elevation of plasma corticosterone and hypothalamic AVP levels induced by water deprivation. These findings showed that in water-deprived rats, nitric oxide synthase inhibition by l-NAME inhibits corticosterone and vasopressin release, suggesting a potent stimulatory role of NO.