Effects of sevoflurane anesthesia and abdominal surgery on the systemic metabolome: a prospective observational study.

BACKGROUND: Metabolic status can be impacted by general anesthesia and surgery. However, the exact effects of general anesthesia and surgery on systemic metabolome remain unclear, which might contribute to postoperative outcomes. METHODS: Five hundred patients who underwent abdominal surgery were included. General anesthesia was mainly maintained with sevoflurane. The end-tidal sevoflurane concentration (ETsevo) was adjusted to maintain BIS (Bispectral index) value between 40 and 60. The mean ETsevo from 20 min after endotracheal intubation to 2 h after the beginning of surgery was calculated for each patient. The patients were further divided into low ETsevo group (mean - SD) and high ETsevo group (mean + SD) to investigate the possible metabolic changes relevant to the amount of sevoflurane exposure. RESULTS: The mean ETsevo of the 500 patients was 1.60% ± 0.34%. Patients with low ETsevo (n = 55) and high ETsevo (n = 59) were selected for metabolomic analysis (1.06% ± 0.13% vs. 2.17% ± 0.16%, P < 0.001). Sevoflurane and abdominal surgery disturbed the tricarboxylic acid cycle as identified by increased citrate and cis-aconitate levels and impacted glycometabolism as identified by increased sucrose and D-glucose levels in these 114 patients. Glutamate metabolism was also impacted by sevoflurane and abdominal surgery in all the patients. In the patients with high ETsevo, levels of L-glutamine, pyroglutamic acid, sphinganine and L-selenocysteine after sevoflurane anesthesia and abdominal surgery were significantly higher than those of the patients with low ETsevo, suggesting that these metabolic changes might be relevant to the amount of sevoflurane exposure. CONCLUSIONS: Sevoflurane anesthesia and abdominal surgery can impact principal metabolic pathways in clinical patients including tricarboxylic acid cycle, glycometabolism and glutamate metabolism. This study may provide a resource data for future studies about metabolism relevant to general anaesthesia and surgeries. TRIAL REGISTRATION: www.chictr.org.cn . identifier: ChiCTR1800014327 .

Selenium Deficiency in COVID-19-A Possible Long-Lasting Toxic Relationship.

In the last two years, there has been a surge in the number of publications on the trace element selenium (Se) and selenocysteine-containing selenoproteins in human health, largely due to the pandemic and the multiple roles that this micronutrient and Se-dependent selenoproteins play in various aspects of the disease [...].

Serum selenium levels in patients with remission and relapse of graves' disease.

OBJECTIVE: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyze the extrathyroidal production of tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and a thyroidal autoimmune process. The aim of this study was to investigate whether serum Se levels may influence the outcome of Graves' disease (GD). DESIGN AND METHODS: 83 patients (77 women, 6 men) with active GD were retrospectively analyzed (mean age 40,0 years). Twenty-four GD patients went into remission and were euthyroid during follow-up (median follow-up: 20.1 months), whereas 59 patients did not go into remission or developed relapse over the following 24 months. TSH receptor autoantibodies (TRAb) were measured using the second generation assay on the basis of human TSH receptor. Se levels were determined at the first visit in our outpatient clinic and were correlated with TRAb levels and clinical outcome of these patients. RESULTS: Median TRAb levels in the group of remission were significantly (p<0.0001) lower than TRAb values in the relapse group (2.1 as compared to 8.6 IU/l). By comparing mean serum Se levels in the remission and relapse group no significant differences were seen (73.0 vs. 71.7 microg/l). Detailed analyses of both groups of patients, however, revealed that highest serum Se levels (>120 microg/l) were seen in the remission group, indicating a positive effect of Se levels on the outcome of GD. In addition, we also compared these results with TRAb levels of these patients. We could show that TRAb levels and serum Se values were positively correlated in the relapse group, whereas a negative correlation of both parameters were seen in the remission group, supporting the idea of a positive effect of Se on thyroidal autoimmune process. CONCLUSION: Our data indicate that high serum Se levels (>120 microg/l) may influence the outcome of GD. This is important, as Se administration trials in GD, which are under discussion need to be performed with Se supplementation at higher dosages than used in autoimmune thyroiditis.

Selenium speciation in human serum and its implications for epidemiologic research: a cross-sectional study.

Observational studies addressing the relation between selenium and human health, particularly cancer risk, yielded inconsistent results, while most recent randomized trials showed a fairly consistent pattern suggesting null or adverse effects of the metalloid. One of the most plausible explanations for such inconsistencies is inadequate exposure assessment in observational studies, commonly carried out by measuring total Se content without taking into account the specific exposure to the individual chemical forms of the metalloid, whose toxic and nutritional properties may vary greatly. Data on the distribution of these species in human blood and their correlation with overall selenium levels are very limited. The concentrations of organic and inorganic selenium species were analyzed in serum of fifty subjects sampled from the general population of the municipality of Modena, northern Italy, aged from 35 to 70 years. Samples were collected during a 30-month period, and determinations of selenium species were carried out using high pressure liquid chromatography coupled with inductively coupled plasma dynamic reaction cell mass spectrometry. The majority of selenium was found to be present as organic species, but the inorganic forms showed higher levels than expected. These species showed limited correlations with age, sex and body mass index, while the organic forms increased in subjects consuming selenium-containing dietary supplements and decreased in smokers. The length of the sample storage period strongly influenced the distribution of selenium compounds, with a clear tendency towards higher inorganic and lower organic selenium levels over time. In multivariate analysis adjusting for potential confounders, total serum selenium correlated with human serum albumin-bound selenium and, in males, with two organic species of the metalloid (selenocysteine and glutathione peroxidase-bound selenium), while little association existed with the other organic forms and the inorganic ones. These findings highlight the potential for exposure misclassification of observational epidemiologic investigations based on overall selenium content in blood and possibly other tissues, and the critical role of the storage conditions for speciation analysis.

Comparative oral dose toxicokinetics of selenium compounds commonly found in selenium accumulator plants.

Consumption of Se accumulator plants by livestock can result in Se intoxication. Recent research indicates that the Se forms most common in Se accumulator plants are selenate and Se-methylselenocysteine (MeSeCys). In this study the absorption, distribution, and elimination kinetics of Se in serum and whole blood of lambs dosed with a single oral dose of (1, 2, 3, or 4 mg Se/kg BW) of sodium selenate or MeSeCys were determined. The Se concentrations in serum and whole blood for both chemical forms of Se followed simple dose-dependent relationships. Se-methylselenocysteine was absorbed more quickly and to a greater extent in whole blood than sodium selenate, as observed by a greater peak Se concentration (Cmax; P < 0.0001), and faster time to peak concentration (Tmax; P < 0.0001) and rate of absorption (P < 0.0001). The rate of absorption and Tmax were also faster (P < 0.0001) in serum of lambs dosed with MeSeCys compared with those dosed sodium selenate at equimolar doses; however, Cmax in serum was greater (P < 0.0001) in lambs dosed with sodium selenate compared with those dosed MeSeCys at equimolar doses. The MeSeCys was absorbed 4 to 5 times faster into serum and 9 to 14 times faster into whole blood at equimolar Se doses. There were dose-dependent increases in the area under the curve (AUC) for Se in serum and whole blood of lambs dosed with both sodium selenate and MeSeCys. In whole blood the MeSeCys was approximately twice as bioavailable as sodium selenate at equimolar doses as observed by the AUC, whereas in serum there were no differences (P > 0.05) in AUC at the same doses. At 168 h postdosing the Se concentration in whole blood remained much greater (P < 0.0001) in lambs dosed with MeSeCys as compared with lambs dosed with sodium selenate; however, the serum Se concentrations were not different between treatments at the same time point. The results presented in this study demonstrate that there are differences between the kinetics of different selenocompounds when orally dosed to sheep. Therefore, in cases of acute selenosis, it is important to understand the chemical form to which an intoxicated animal was exposed when determining the importance and meaning of Se concentration in serum or whole blood obtained at various times postexposure.

Effects of dietary selenium supplementation on tissue selenium distribution and glutathione peroxidase activity in Chinese Ring necked Pheasants.

The objective of this study was to determine the concentration of total selenium (Se) and the proportions of total Se comprised as selenomethionine (SeMet) and selenocysteine (SeCys) in the postmortem tissues of female pheasants (Phasianus Colchicus Torquator) offered diets that contained graded additions of selenised-enriched yeast (SY) or a single comparative dose of sodium selenite (SS). Thiobarbituric acid reactive substances (TBARS) and tissue glutathione peroxidase (GSH-Px) activity of breast (Pectoralis Major) were assessed at 0 and 5 days postmortem. A total of 216 female pheasant chicks were enrolled into the study. Twenty-four birds were euthanased at the start of the study, and samples of blood, breast muscle, leg muscle (M. Peroneus Longus and M. Gastrocnemius), heart, liver, kidney and gizzard were collected for determination of total Se. Remaining birds were blocked by live weight and randomly allocated to one of four dietary treatments (n = 48 birds/treatment) that either differed in Se source (SY v. SS) or dose (control (0.17 mg total Se/kg), SY-L and SS-L (0.3 mg/kg total Se as SY and SS, respectively) and SY-H (0.45 mg total Se/kg)). Following 42 and 91 days of treatment, 24 birds per treatment were euthanased, and samples of blood, breast muscle, leg muscle, heart, liver, kidney and gizzard were retained for determination of total Se and the proportion of total Se comprised as SeMet or SeCys. Whole blood GSH-Px activity was determined at each time point. Tissue GSH-Px activity and TBARS were determined in breast tissue at the end of the study. There were increases in both blood and tissues to the graded addition of SY to the diet (P < 0.001), but the same responses were not apparent with the blood and tissues of selenite-supplemented birds receiving a comparable dose (SY-L v. SS-L). Although there were differences between tissue types in the distribution of SeMet and SeCys, there were few differences between treatments. There were effects of treatment on erythrocyte GSH-Px activity (P = 0.012) with values being higher in treatments SY-H and SS-L when compared with the negative control and treatment SY-L. There were no effects of treatment on tissue GSH-Px activity, which is reflected in the overall lack of any treatment effects on TBARS.

Effect of selenium source and dose on selenium status of mature horses.

This study was conducted to determine the effects of either dietary Se source or dose on the Se status of horses. Twenty-five mature horses were blocked by BW and randomly allocated to 1 of 5 dietary treatments that comprised the same basal diet that differed only in Se source or dose. Treatments were as follows: negative control (0.085 mg of Se/kg of DM), 3 different dietary concentrations of supplemental organic Se (Se yeast; 0.2, 0.3, and 0.4 mg of total Se/kg of DM), and positive control (0.3 mg of total Se/kg of DM) supplemented with Na selenite. Horses initially received the control diet (6 kg of grass hay and 3 kg of concentrate per horse daily) for 56 d to allow diet adaptation. After the period of diet adaptation, horses were offered their respective treatments for a continuous period of 112 d. Jugular venous blood samples were collected before the morning feed on d 0, 28, 56, 84, and 112. Whole blood and plasma were analyzed for total Se, glutathione peroxidase activity in whole blood (GPX-1) and plasma, and thyroid hormones (thyroxine and triiodothyronine) in plasma. The proportion of total Se as selenomethionine (SeMet) or selenocysteine in pooled whole blood and plasma samples was determined on d 0, 56, and 112. Data were analyzed as repeated measures. Total Se in blood and plasma and GPX-1 activity were greater in all supplemented horses (P < 0.001, except P < 0.01 for GPX-1 in horses supplemented with the least dose of Se yeast) with a linear dose effect of Se yeast for whole blood and plasma Se (P < 0.001) and a quadratic dose effect (P < 0.05) for whole blood GPX-1 activity. A plateau for total Se in plasma was achieved within 75 to 90 d, although this was not observed in blood total Se or GPX-1 activity. On d 84 and 112, horses supplemented with Se yeast showed greater total Se in blood (P < 0.05) compared with horses supplemented with Na selenite, and a source effect (P < 0.05) was observed in the relationship between total blood Se and GPX-1 activity. Selenocysteine (the predominant form of Se in whole blood and plasma) increased in all horses supplemented with Se. The SeMet content of whole blood and plasma increased in horses supplemented with Se yeast, but it was not observed in those supplemented with selenite. The rate of increase in SeMet over time was greater in whole blood (P < 0.05) and plasma (P = 0.10) with the Se yeast product. In conclusion, Se yeast was more effective than Na selenite in increasing total Se in blood, mainly as consequence of a greater increase of the proportion of Se comprised as SeMet, but it did not modify GPX-1 activity.

Speciation of selenomethionine and selenocystine using online micro-column containing Cu(II) loaded nanometer-sized Al2O3 coupled with ICP-MS detection.

A flow injection online speciation procedure by using micro-column packed with Cu(II) loaded nanometer-sized Al(2)O(3) coupled to inductively coupled plasma mass spectrometry (ICP-MS) for the separation and determination of selenomethionine (SeMet) and selenocystine (SeCys(2)) has been developed. The main factors affecting the separation and preconcentration of SeMet and SeCys(2) including pH value, sample flow rate, eluent concentration, eluent volume and flow rate, and interfering ions have been investigated. It was found that SeCys(2) could be selectively retained by micro-column packed with Cu(II) loaded nanometer-sized Al(2)O(3) at pH 4.0, and the retained SeCys(2) could be eluted by 1.0 mol L(-1) HNO(3), while SeMet was not retained and passed through the micro-column directly at this pH. Both SeMet and SeCys(2) could be quantitatively adsorbed by the micro-column at pH 9.0, and the retained SeMet and SeCys(2) could be easily eluted with 1.0 mol L(-1) HNO(3). The content of SeMet was obtained by subtracting the SeCys(2) from the total content of seleno amino acids. With the enrichment factor of 7.8 and 7.7, the limits of detection (LODs) for SeMet and SeCys(2) were found to be 24 pg Se mL(-1) and 21 pg Se mL(-1), respectively. The relative standard deviations (RSDs) for SeCys(2) and SeMet with seven replicate determinations of 1.0 ng mL(-1) SeMet and SeCys(2), were 2.1% and 1.6%, respectively, the sampling frequency of 8h(-1) was obtained. The proposed method was applied to the speciation of SeMet and SeCys(2) in selenized yeast, human urine and serum with satisfactory results.

Determination of selenomethionine and selenocysteine in human serum using speciated isotope dilution-capillary HPLC-inductively coupled plasma collision cell mass spectrometry.

A method for the accurate determination of selenoamino acids in human serum by HPLC-ICPMS was developed using the species-specific isotope dilution analysis principle. A serum sample was enzymatically digested with a mixture of lipase and protease after derivatization of the selenocysteine residues with iodoacetamide. The selenoamino acid fraction was isolated by size exclusion LC followed by the separation of selenomethionine and the carboxymethylated selenocysteine by capillary HPLC. The isotope-specific determination of 77Se and 80Se was achieved on-line by ICP collision cell MS allowing the removal of polyatomic interferences. Quantification was carried out by isotope dilution using a 77Se-labeled selenomethionine spike and the determination of the 77Se/80Se ratio in the cHPLC selenomethionine peak. The accurately determined selenomethionine was used as an internal standard for the selenocysteine determination from the same chromatogram. The modification of the previously developed cHPLC-ICPMS interface allowed the reduction of the absolute detection limits twice (down to the 75-fg level), which resulted in the lowest ever reported procedural detection limits (below 0.5 ng g(-1) for a 450-mg serum sample). The precision was less than 5% RSD. The method was validated by the mass balance of selenium (amino acid incorporated vs total).

High-performance liquid chromatographic determination of selenocysteine with the fluorescent reagent, N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid.

The method described is based on derivatization of selenocysteine with N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid and responds linearly to selenocysteine spiked into plasma. Recovery is insensitive to inter-individual variation or use of serum versus plasma, but is decreased by hemolysis. The derivative is stable for at least three days. The total imprecision of determinations in plasma was 0.8-2.1% (coefficient of variation) over the range of 6-30 microM selenocysteine, with a detection limit of 0.4 microM (3 x S.D.). There was no significant interference from plasma thiols. This appears to be the first report of the selective reaction of free selenocysteine with a fluorescent reagent. This simple method works well in plasma and serum and may be adaptable to other types of samples.