Vitamin E and Selenium Treatment Alleviates Saline Environment-Induced Oxidative Stress through Enhanced Antioxidants and Growth Performance in Suckling Kids of Beetal Goats.

Salinity is a worldwide, threatening problem affecting socioeconomic status globally. Saline land comprises salt content in soil, plants, and drinking water. Livestock farming is the worthy option for proper utilization of saline land in a cost-effective approach. Animals reared on this land experience a variety of stresses. Such stresses promote oxidative stress and reduced animal performance. The purpose of this study was to investigate the antioxidative function of vitamin E and selenium (Se) on pregnant/nonpregnant animals reared on the saline environment. A total of 36 multiparous pregnant (n = 18) and nonpregnant (n = 18) goats weighing about 38-45 (average 41.5) kg were equally divided into control and supplemented groups. The experiment lasted from 120 days of gestation to 15 days after parturition for pregnant goats and 0 to 45 days for nonpregnant cyclic goats (>50 days post-kidding). The supplemented group was administered vitamin E (1000 mg/kg BW) and selenium (3 mg/50 kg BW), while the control group was kept on normal saline (0.9% NaCl) with the same route 15 days apart. The blood samples were collected with 15 days apart during the entire experimental period of 45 days and subjected to assessment of enzymatic/nonenzymatic antioxidants, hydrolytic enzymes, oxidants, stress metabolic biomarkers, Se, and progesterone concentration of (pregnant) animals. Results revealed that vitamin E and Se supplementation significantly enhanced the activity of enzymatic (catalase and peroxidase) and nonenzymatic antioxidants such as total phenolic/flavonoid content and vitamin C and increased blood plasma level of Se concentration in comparison with the control group (P < 0.01). Exposure to antioxidant supplementation mitigated lipid peroxidation and enhanced progesterone level and total antioxidant capacity (P < 0.01) as compared to the control group in pregnant goats. Administration of vitamin E and selenium promoted kid survival rate (100%) along with increased initial birth weight, daily average weight gain, and total weight gain in comparison with the control group. Besides, the twinning rate and sex ratio were also recorded in pregnant animals. It is concluded that vitamin E and Se supplementation ameliorated salinity-induced oxidative stress, improved antioxidant status, and enhanced reproductive and growth performance of suckling kids reared on saline land.

Simultaneous Determination of Phenolic Compounds in Plasma by LC-ESI-MS/MS and Their Bioavailability after the Ingestion of Table Olives.

The role attributed to polyphenols on human health needs to be correlated with their plasmatic concentrations after food consumption. Then, a method based on liquid-liquid extraction followed by highly sensitive LC-ESI-MS/MS analysis was developed to determinate 16 phenolic compounds in plasma. Validation gave appropriate recovery, matrix effect (80%-120%), linear correlation (R2 > 0.995), precision (<15%), LOQ (0.04-2.51 nM), and short chromatographic run. The method was verified after the administration of Arbequina table olives to rats. A single dose of destoned olives was given by gavage, and plasmatic concentrations of polyphenols were analyzed at 30 min. Interestingly, the profile found in plasma greatly differed from that of the olives. Plasmatic concentrations, from highest to lowest, were salidroside, p-coumaric acid, hydroxytyrosol, verbascoside, tyrosol, luteolin, and luteolin-7-O-glucoside. In conclusion, a simple and robust method was developed, enabling the identification and quantification of unaltered polyphenols in plasma after olives consumption, thus demonstrating its suitability for pharmacokinetics studies.

LC-MS/MS method for the determination of erianin in rat plasma: Application to a pharmacokinetic study.

Erianin is one of the bibenzyl ingredients isolated from Dctidrobium chrysotoxum Lindl. In recent years, erianin has attracted attention owing to its antitumor activity. In this study, an LC-MS/MS method was established to measure erianin in rat plasma. Gigantol was used as the internal standard. A Waters Acquity UPLC BEH C18 column was employed for chromatographic separation. The mobile phase consisted of water containing 0.1% formic acid and acetonitrile with a gradient elution at the flow rate of 0.4 ml/min. Selective reaction monitoring mode was used for quantitative analysis of erianin in positive electrospray ionization. In the concentration range of 0.1-1200 ng/ml, erianin in rat plasma was linear with correlation coefficient >0.999. The lowest limit of quantification was 0.1 ng/ml. The intra- and inter-day RSDs were <9.69%, while the RE was in the range of -8.59-11.24%. The mean recovery was >85.37%. Erianin was stable in rat plasma after storage under certain conditions. The validated method was demonstrated to be selective, sensitive and reliable, and has been successfully applied to pharmacokinetic study of erianin in rat plasma. Erianin was rapidly eliminated from rat plasma with a short half-life (〜1.5 h) and low oral bioavailability (8.7%).

Immobilization of tyrosinase on Fe3o4@Au core-shell nanoparticles as bio-probe for detection of dopamine, phenol and catechol.

An optical bio-probe based on the immobilized tyrosinase on the surface of Fe3O4@Au was described for the detection of dopamine, phenol and catechol. The prepared bio-probe (Fe3O4@Au@tyrosinase) was characterized by means such as TEM, SEM, VSM, DLS and TGA. In the presence of the bio-probe, the phenol, catechol and dopamine were converted to benzoquinone, o-quinone and dopaquinone, and the fluorescence spectra appeared at 308 nm, 329 nm and 336 nm with ex = 270 nm, respectively. However, by increasing the concentration of phenolic compounds in the bio-probe, the amount of products (benzoquinone, o-quinone and dopaquinone) was increased which was the reason for the increase in fluorescence intensity. Using this mechanism, a bio-probe was designed such that the intensity of the fluorescence spectra increased proportionally with the increase of the substrate concentrations after different time periods. The 0.003 mg/mL of tyrosinase was loaded on 1.65 mg/mL of the Fe3O4@Au. The highest performance for a bio-probe was demonstrated at room temperature and pH 6.8. By investigating the characteristics of the response of the bio-probe to different phenolic compounds, it was found that the bio-probe had a linear response in the concentration range 5.0-75.0 µM, 10.0-100.0 µM for phenol and dopamine and 50.0-500.0 M for catechol. The Michaelis-Menten constant (Km) of the bio-probe was calculated as 0.6 µM. Finally, the bio-probe seems to be stable and efficient even after about 2 months. A novel and easy method for the detection of dopamine, phenol and catechol by florescence that uses oxide capability to identify the phenolic compounds was introduced.

Effect of Lactobacillus Rhamnosus on serum uremic toxins (phenol and P-Cresol) in hemodialysis patients: A double blind randomized clinical trial.

BACKGROUND: Uremic toxins such as p-cresol and phenol are suggested to be associated with higher mortality in hemodialysis patients. The aim of this study was to investigate the effects of probiotics on some serum uremic toxin levels in hemodialysis patients. METHODS: Patients undergoing hemodialysis in a university dialysis center were enrolled in this randomized controlled double blind clinical trial. The patients received probiotic (Lactobacillus Rhamnosus) for duration of 4 weeks. All data were presented as the mean ± SD. Statistical analyses were performed by SPSS statistical software. Paired t-test was used to compare pre- and post-treatment p-cresol levels. P values less than .05 were considered statistically significant. RESULTS: A total of 42 hemodialysis patients (32 male and 10 female) were enrolled in this study. The mean ± SD age of the patients in Lactobacillus Rhamnosus and placebo groups were 57.05 ± 13.96 and 59.67 ± 15.04 years, respectively. Values of uremic toxins before treatment did not differ statistically between groups but they were significantly lower in Lactobacillus Rhamnosus group compared with placebo group (P < .05). Total Phenol and p-cresol levels were associated with sodium, energy, carbohydrate, fat and protein intake and fiber consumption, accompanying by hemodialysis hours per week in linear regression analyses. CONCLUSIONS: This study demonstrated that probiotics could be a promising target in hemodialysis patients with the capability of decreasing serum phenolic uremic toxins in this population. TRIAL REGISTRATION: IRCT20154182017N21 Date:09/12/2016.

Fatal Ingestion of Chlumsky Disinfectant Solution.

A 32-year-old pregnant woman in the 25th week of pregnancy underwent oral glucose tolerance screening at the diabetologist's. Later that day, she was found dead in her apartment possibly poisoned with Chlumsky disinfectant solution (solutio phenoli camphorata). An autopsy revealed chemical burns in the digestive system. The lungs and the brain showed signs of severe edema. The blood of the woman and fetus was analyzed using gas chromatography with mass spectrometry and revealed phenol, its metabolites (phenyl glucuronide and phenyl sulfate) and camphor. No ethanol was found in the blood samples. Both phenol and camphor are contained in Chlumsky disinfectant solution, which is used for disinfecting surgical equipment in healthcare facilities. Further investigation revealed that the deceased woman had been accidentally administered a disinfectant instead of a glucose solution by the nurse, which resulted in acute intoxication followed by the death of the pregnant woman and the fetus.

Potentiation of the bioavailability of blueberry phenolic compounds by co-ingested grape phenolic compounds in mice, revealed by targeted metabolomic profiling in plasma and feces.

The low bioavailability of dietary phenolic compounds, resulting from poor absorption and high rates of metabolism and excretion, is a concern as it can limit their potential beneficial effects on health. Targeted metabolomic profiling in plasma and feces of mice supplemented for 15 days with a blueberry extract, a grape extract or their combination revealed significantly increased plasma concentrations (3-5 fold) of blueberry phenolic metabolites in the presence of a co-ingested grape extract, associated with an equivalent decrease in their appearance in feces. Additionally, the repeated daily administration of the blueberry-grape combination significantly increased plasma phenolic concentrations (2-3-fold) compared to animals receiving only a single acute dose, with no such increase being observed with individual extracts. These findings highlight a positive interaction between blueberry and grape constituents, in which the grape extract enhanced the absorption of blueberry phenolic compounds. This study provides for the first time in vivo evidence of such an interaction occurring between co-ingested phenolic compounds from fruit extracts leading to their improved bioavailability.

[Clinical and laboratory diagnostic criteria of chronic glomerular and tubulointerstitial kidney disorders associated with exposure to metals and oxygen organic compounds of technogenic origin].

Complex clinical, functional an laboratory examination of children living under unacceptable risk conditions due to aerogenous exposure to cadmium, chromium, lead and phenol revealed that kidney diseases associated with exposure to metals and phenol develop in children with genetic predisposition to disordered biotransformation of chemicals--polymorphism of genes CYPOX, RCYT 450, SULTA1 in homozygous and heterozygous variants. Increased levels of chemicals in blood causes microcirculation disorders in renal cortex, direct toxic effect in nephrons, suppresses activity of anitoxidant defense on cellular and systemic levels. The authors specified pathogenetically based complex of clinical and laboratory diagnostic markers of chronic kidney diseases associated with exposure to metals (cadmium, chromium, lead) and oxygen-containing (phenol) organic compounds.

Pore size--a key property for selective toxin removal in blood purification.

PURPOSE: Extracorporeal blood purification systems based on combined membrane/adsorption technologies are used in acute liver failure to replace detoxification as well as to remove inflammatory mediators in sepsis patients. In addition to coating and chemical modification of the surface, pore size significantly controls the selectivity of adsorption materials. METHODS: This study addresses the adsorption of albumin bound liver toxins, cytokines, and representative plasma compounds on three adsorbents which differ only in pore size distribution. All three adsorbents are based on hydrophobic poly(styrene-divinylbenzene) copolymer matrices and have mean pore sizes of 15, 30, and 100 nm. RESULTS: The pores of adsorbents act as molecular sieves and prevent the entry of molecules that are larger than their molecular cut-off. The results of this study reveal that adsorbents based on styrene-divinylbenzene polymers with 15 nm pores are suitable for cytokine removal, and the same adsorbents with 30-40 nm pores are the best choice for the removal of albumin-bound toxins in the case of liver failure. Adsorbents with very large pores lack selectivity which leads to uncontrolled adsorption of all plasma proteins. Therefore, hydrophobic adsorbents with large pores offer inadequate plasma compatibility and do not fulfill the requirements for blood purification. CONCLUSIONS: Biocompatibility and efficiency of adsorbents used for blood purification can improved by fine tuning of adsorbent surface pore distributions.

Activation-dependent adsorption of cytokines and toxins related to liver failure to carbon beads.

In the course of severe pathological conditions, such as acute liver failure and sepsis, toxic metabolites and mediators of inflammation are released into the patient's circulation. One option for the supportive treatment of these conditions is plasmapheresis, in which plasma, after being separated from the cellular components of the blood, is cleansed by adsorption of harmful molecules on polymers or activated carbon. In this work, the adsorption characteristics of activated carbon beads with levels of activation ranging from 0 to 86% were assessed for both hydrophobic compounds accumulating in liver failure (bilirubin, cholic acid, phenol and tryptophan) and cytokines (tumor necrosis factor α and interleukin-6). Progressive activation resulted in significant gradual reduction of both bulk density and mean particle size, in an increase in the specific surface area, and to changes in pore size distribution with progressive broadening of micropores. These structural changes went hand in hand with enhanced adsorption of small adsorbates, such as IL-6 and cholic acid and, to a lesser extent, also of large molecules, such as TNF-α.

Determination of uremic solutes in biological fluids of chronic kidney disease patients by HPLC assay.

During chronic kidney disease (CKD), solutes called uremic solutes, accumulate in blood and tissues of patients. We developed an HPLC method for the simultaneous determination of several uremic solutes of clinical interest in biological fluids: phenol (Pol), indole-3-acetic acid (3-IAA), p-cresol (p-C), indoxyl sulfate (3-INDS) and p-cresol sulfate (p-CS). These solutes were separated by ion-pairing HPLC using an isocratic flow and quantified with a fluorescence detection. The mean serum concentrations of 3-IAA, 3-INDS and p-CS were 2.12, 1.03 and 13.03 µM respectively in healthy subjects, 3.21, 17.45 and 73.47 µM in non hemodialyzed stage 3-5 CKD patients and 5.9, 81.04 and 120.54 µM in hemodialyzed patients (stage 5D). We found no Pol and no p-C in any population. The limits of quantification for 3-IAA, 3-INDS, and p-CS were 0.83, 0.72, and 3.2 µM respectively. The within-day CVs were between 1.23 and 3.12% for 3-IAA, 0.98 and 2% for 3-INDS, and 1.25 and 3.01% for p-CS. The between-day CVs were between 1.78 and 5.48% for 3-IAA, 1.45 and 4.54% for 3-INDS, and 1.19 and 6.36% for p-CS. This HPLC method permits the simultaneous and quick quantification of several uremic solutes for daily analysis of large numbers of samples.

[Substantiating the blood concentrations of phenol and alkylphenols (o-, m-, and p-cresols) providing the acceptable risk to human health].

The paper considers the current nontraditional approaches to revealing the causal effects and criteria for significance of an exposure-response relationship. The study has used the elements of methodology for assessing the risk and the techniques of environmental epidemiology to examine causal effects. A blood toxicant-response marker relationship was assessed and the quantitative characteristics of the association between the concentrations of the test compounds and the risk of noxious effects were ascertained. On the basis of exposure marker-response marker models, the authors revealed the priority types of functional changes and established the blood concentrations of phenol and m- and n-cresols at an acceptable risk level.

Study of the metabolism of estragole in humans consuming fennel tea.

The metabolism of the potent carcinogen estragole was investigated in humans after consumption of fennel tea by analyses of its metabolites in blood plasma and urine. Stable isotope dilution assays based on LC-MS/MS detection revealed that 1'-hydroxylation of estragole happened very fast as the concentration of conjugated 1'-hydroxyestragole in urine peaked after 1.5 h, whereas it was no longer detectable after 10 h. Besides the formation of less than 0.41% conjugated 1'-hydroxyestragole of the estragole dose administered, the further metabolite p-allylphenol was generated from estragole in a higher percentage (17%). Both metabolites were also detected in blood plasma in less than 0.75-2.5 h after consumption of fennel tea. In contrast to this, no estragole was present in these samples above its detection limit. From the results, it can be concluded that an excess of the major fennel odorant trans-anethole principally does not interfere with estragole metabolism, whereas influences on the quantitative composition of metabolites cannot be excluded. The presence of a sulfuric acid conjugate of estragole could not be confirmed, possibly due to its high reactivity and lability.

Use of online microdialysis sampling to determine the in vivo rate of phenol glucuronidation in rainbow trout.

A quantitative microdialysis (MD) sampling method was used to study phenol (PH) glucuronidation in vivo in rainbow trout. The method employs internal calibrators to account for changes in MD probe performance (in vitro-to-in vivo and sample-to-sample) and yields data of high temporal resolution that are well suited for developing kinetic models. Initially, trout were dosed with phenyl glucuronide (PG) by intravascular infusion for 24 h and then depurated for 48 h. Measured concentrations of PG in blood were well described by a one-compartment clearance-volume model. Massbalance calculations showed that 93% of infused PG was eliminated in urine during the depuration period. Peak concentrations of PG in urine averaged 3.4 times higher than those in blood, and the fitted PG clearance constant (15.7 ml/kg/h) was about 2.6 times higher than the reported glomerular filtration rate for trout. These findings confirm earlier work suggesting that PG is actively secreted by the trout kidney. In a second set of experiments, trout were exposed continuously to PH in water. In vivo rate constants for PH glucuronidation were estimated using a pair of linked (PH and PG) one-compartment clearance-volume models. Expressed on a whole-fish basis, the glucuronidation rate averaged 0.049/h, which was about 7% of the total rate of PH elimination. This study demonstrates the utility of quantitative MD sampling for kinetic studies of xenobiotic metabolism in fish.

Dietary galacto-oligosaccharides mixture can suppress serum phenol and p-cresol levels in rats fed tyrosine diet.

Phenols (phenol and p-cresol) are amino acid metabolites produced by intestinal bacteria. Some reports have demonstrated that the accumulation of phenols in the serum has toxic effects in renal failure patients. In this study, we found that phenols accumulated in the serum of rats given a tyrosine diet, and that dietary intake of a galacto-oligosaccharide mixture (GOS) suppressed the accumulation of phenols in serum. Rats were fed a basal diet, tyrosine diet (basal diet with 2.5% tyrosine) or GOS diet (tyrosine diet with 5% GOS) for 2 wk. The concentrations of phenols in the feces, cecal contents, serum and urine were determined. Concentrations of phenols in the serum, cecal contents and feces from rats fed the tyrosine diet were significantly higher than those in rats fed the basal diet. The concentrations of phenols in feces, cecal contents and serum, and urinary excretion in the GOS diet group were significantly lower than those in the tyrosine diet group. The pH of cecal contents was decreased by GOS intake. Furthermore, the serum concentrations of phenols were closely correlated with cecal concentrations. This finding suggested that concentrations of phenols in the serum reflected phenol production in the cecum contents. These results showed that dietary intake of GOS could modify the intestinal environment, and suppress the production of phenols in the intestinal tract and the accumulation of phenols in the serum. Thus, GOS may help improve the quality of life (QOL) of patients with renal failure.

Bioavailability and efficiency of rutin as an antioxidant: a human supplementation study.

OBJECTIVE: To determine the potential antioxidant effect of rutin (quercetin-3-O-beta-rutinoside) supplementation. DESIGN: A 6-week randomized single-blind placebo controlled trial was conducted; 500 mg rutin supplement was compared to an equivalent amount of glucose placebo. In addition, a pharmacokinetic study was carried out. SETTING: The Rowett Research Institute, Aberdeen, UK. SUBJECTS: Eighteen healthy non-obese normocholesterolaemic female volunteers in the age range 18-48 y. MAIN OUTCOME MEASURES: Plasma flavonoids, ascorbic acid, tocopherols and carotenoids, plasma antioxidant capacity, lymphocyte DNA damage, blood chemistry and haematology, liver function tests, urinary malondialdehyde, 8-hydroxy-2-deoxyguanosine and 8-iso-prostaglandin F2alpha. RESULTS: Eighteen volunteers completed the trial. Rutin supplementation did not induce any adverse changes in blood chemistry or indices of liver function. Plasma flavonoids were significantly elevated in the rutin-supplemented group. Endogenous oxidation of pyrimidines was significantly decreased in both rutin- and placebo-treated volunteers. There was no significant change in the level of urinary 8-hydroxy-2'-deoxyguanosine or urinary malondialdehyde in either group. A linear correlation was observed between urinary malondialdehyde and urinary 8-iso-prostaglandin F2alpha (R = 0.54, P<0.01). CONCLUSION: Six weeks' rutin supplementation significantly elevated the levels of three plasma flavonoids (quercetin. kaempferol and isorhamnetin) but there was no significant change in plasma antioxidant status. The decrease in the level of endogenous base oxidation in lymphocyte DNA seen in both the placebo- and rutin-supplemented subjects may reflect seasonal changes in other dietary antioxidants.

Disposition of propofol between red blood cells, plasma, brain and cerebrospinal fluid in rabbits.

The disposition of propofol in the blood and brain of New Zealand rabbits was studied in three groups of six rabbits. One group received a single anaesthetic dose; a second group received a 1-h infusion; and a third group was studied after the rabbits were judged to have recovered from a 1-h infusion. There was a high concentration of propofol in the red blood cell fraction and in the brain, however, the red blood cell concentration largely exceeded the one found in the brain in all groups of animals. This is consistent with the high fat solubility of diisopropylphenol. The possible effects of propofol sequestered in red blood cells is discussed.

Influence of gender and acetone pretreatment on benzene metabolism in mice exposed by nose-only inhalation.

Benzene (BZ) requires oxidative metabolism catalyzed by cytochrome P-450 2E1 (CYP 2E1) to exert its hematotoxic and genotoxic effects. We previously reported that male mice have a two-fold higher maximum rate of BZ oxidation compared with female mice; this correlates with the greater sensitivity of males to the genotoxic effects of BZ as measured by micronuclei induction and sister chromatid exchanges. The aim of this study was to quantitate levels of BZ metabolites in urine and tissues, and to determine whether the higher maximum rate of BZ oxidation in male mice would be reflected in higher levels of hydroxylated BZ metabolites in tissues and water-soluble metabolites in urine. Male and female B6C3F, mice were exposed to 100 or 600 ppm 14C-BZ by nose-only inhalation for 6 h. An additional group of male mice was pretreated with 1% acetone in drinking water for 8 d prior to exposure to 600 ppm BZ; this group was used to evaluate the effect of induction of CYP 2E1 on urine and tissue levels of BZ and its hydroxylated metabolites. BZ, phenol (PHE), and hydroquinone (HQ) were quantified in blood, liver, and bone marrow during exposure and postexposure, and water-soluble metabolites were analyzed in urine in the 48 h after exposure. Male mice exhibited a higher flux of BZ metabolism through the HQ pathway compared with females after exposure to either 100 ppm BZ (32.0 2.03 vs. 19.8 2.7%) or 600 ppm BZ (14.7 1.42 vs. 7.94 + 0.76%). Acetone pretreatment to induce CYP 2E1 resulted in a significant increase in both the percent and mass of urinary HQ glucuronide and muconic acid in male mice exposed to 600 ppm BZ. This increase was paralleled by three- to fourfold higher steady-state concentrations of PHE and HQ in blood and bone marrow of acetone-pretreated mice compared with untreated mice. These results indicate that the higher maximum rate of BZ metabolism in male mice is paralleled by a greater proportion of the total flux of BZ through the pathway for HQ formation, suggesting that the metabolites formed along this pathway may be responsible for the genotoxicity observed following BZ exposure.