Hippuric Acid Research Articles

Untargeted metabolomics unravel serum metabolic alterations in smokers with hypertension.

Background: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis. Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index. Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.

Identification of Differential Metabolites Between Type 2 Diabetes and Postchronic Pancreatitis Diabetes (Type 3c) Based on an Untargeted Metabolomics Approach.

A nontargeted metabolomics approach was established to characterize serum metabolic profile in type 3c diabetes mellitus (T3cDM) secondary to chronic pancreatitis and compare with T2DM. Forty patients were recruited for metabolite analysis based on liquid chromatography-mass spectrometry. Cluster heatmap and KEGG metabolic pathway enrichment analysis were used to analyze the specific and differential metabolites. The receiver operating characteristics (ROCs) were generated and correlation analysis with clinical data was conducted. Metabolites including sphingosine, lipids, carnitine, bile acid, and hippuric acid were found to be different between T2DM and T3cDM, mainly enriched in bile acid biosynthesis, fatty acid biosynthesis, and sphingolipid metabolic pathways. The ROCs were generated with an area under the curve of 0.907 (95% confidence interval, 0.726-1) for the model with 15 metabolites. T3cDM is characterized by increased sphingosine, carnitine, bile acid, and most lipids, providing novel biomarkers for clinical diagnosis and a future direction in research on pathophysiological mechanisms.

Disentangling the Complexity of Nutrition, Frailty and Gut Microbial Pathways during Aging: A Focus on Hippuric Acid.

Hippuric acid (HA) is a metabolite resulting from the hepatic glycine conjugation of benzoic acid (BA) or from the gut bacterial metabolism of phenylalanine. BA is generally produced by gut microbial metabolic pathways after the ingestion of foods of vegetal origin rich in polyphenolic compounds, namely, chlorogenic acids or epicatechins. It can also be present in foods, either naturally or artificially added as a preservative. The plasma and urine HA levels have been used in nutritional research for estimating the habitual fruit and vegetable intake, especially in children and in patients with metabolic diseases. HA has also been proposed as a biomarker of aging, since its levels in the plasma and urine can be influenced by the presence of several age-related conditions, including frailty, sarcopenia and cognitive impairment. Subjects with physical frailty generally exhibit reduced plasma and urine levels of HA, despite the fact that HA excretion tends to increase with aging. Conversely, subjects with chronic kidney disease exhibit reduced HA clearance, with HA retention that may exert toxic effects on the circulation, brain and kidneys. With regard to older patients with frailty and multimorbidity, interpreting the HA levels in the plasma and urine may result particularly challenging because HA is at the crossroads between diet, gut microbiota, liver and kidney function. Although these considerations may not make HA the ideal biomarker of aging trajectories, the study of its metabolism and clearance in older subjects may provide valuable information for disentangling the complex interaction between diet, gut microbiota, frailty and multimorbidity.

Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment.

An understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.

Zn(OCOCH<sub>3</sub>)<sub>2</sub>·2H<sub>2</sub>O Catalysed Efficient Preparation of 2-Phenyl-4-Arylmethylidene-5-Oxazolinones under Ultrasonic Condition

2-Phenyl-4-arylmethylidene-5-oxazolinones were synthesized in very high yield by subjecting a mixture of an aryl aldehyde/heterocyclic aldehyde/cinnamaldehyde and hippuric acid in anhydrous acetic anhydride and catalytic Zn(OCOCH<sub>3</sub>)<sub>2</sub><strong>·</strong>2H<sub>2</sub>O to ultrasonication at 35 KHz for 4 to 8 min. This method has many advantages: use of a green catalyst; yields are high, involves easy workup procedure, is energy efficient and economically feasible.

Correlation between Saliva Levels and Serum Levels of Free Uremic Toxins in Healthy Volunteers

The objective of the present study was to investigate the putative correlation between the saliva concentration and free serum concentration for 10 uremic toxins (UTs; eight protein-bound solutes: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), hippuric acid (HA), indole-3-acetic acid (3-IAA), indoxyl sulfate (I3S), kynurenic acid (KA), kynurenine (KYN), p-cresyl glucuronide (pCG), and p-cresyl sulfate (pCS); two free, water-soluble, low-molecular weight solutes: phenylacetylglutamine (PAGN) and trimethylamine N-oxide (TMAO); and three precursors: tyrosine (Tyr), phenylalanine, and tryptophan). Saliva samples and blood samples were collected simultaneously from 18 healthy volunteers. After the addition of internal standards, 50 µL of saliva or serum were precipitated with methanol. UTs and precursors were quantified using a validated LC-MS/MS method. The saliva-serum correlation was statistically significant (according to Spearman's coefficient) for six UTs (TMAO, HA, I3S, pCS, 3-IAA, and CMPF). Tyr presented a weak saliva-serum correlation (p = 0.08), whereas the other two precursors did not show a saliva-serum correlation. For three UTs (KYN, KA and pCG), we were unable to test the correlation since the saliva or serum levels were too low in many of the volunteers. The present study is the first to report on the saliva concentrations of TMAO, KYN, HA, PAGN, pCG, and 3-IAA.

Metabolomic identification of predictive and early biomarkers of cisplatin-induced acute kidney injury in adult head and neck cancer patients.

Cisplatin causes acute kidney injury (AKI) in approximately one third of patients. Serum creatinine and urinary output are poor markers of cisplatin-induced AKI. Metabolomics was utilized to identify predictive or early diagnostic biomarkers of cisplatin-induced AKI. Thirty-one adult head and neck cancer patients receiving cisplatin (dose ≥70 mg/m2) were recruited for metabolomics analysis. Urine and serum samples were collected prior to cisplatin (pre), 24-48 h after cisplatin (24-48 h) and 5-14 days (post) after cisplatin. Based on serum creatinine concentrations measured at the post timepoint, 11/31 patients were classified with clinical AKI. Untargeted metabolomics was performed using liquid chromatography-mass spectrometry (LC-MS). Metabolic discrimination was observed between "AKI" patients and "no AKI" patients at all timepoints. Urinary glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate were significantly different between AKI patients and no AKI patients prior to cisplatin infusion. Urinary glycine and hippuric acid sulfate were lower (-2.22-fold and -8.85-fold), whereas 3-hydroxydecanedioc acid and suberate were higher (3.62-fold and 1.91-fold) in AKI patients relative to no AKI patients. Several urine and serum metabolites were found to be altered 24-48 h following cisplatin infusion, particularly metabolites involved with mitochondrial energetics. We propose glycine, hippuric acid sulfate, 3-hydroxydecanedioc acid and suberate as predictive biomarkers of predisposition to cisplatin-induced AKI. Metabolites indicative of mitochondrial dysfunction may serve as early markers of subclinical AKI.

Metabolomics Profiling of Age-Associated Metabolites in Malay Population.

Aging is a complex process characterized by progressive loss of functional abilities due to the accumulation of molecular damages. Metabolomics could offer novel insights into the predictors and mechanisms of aging. This cross-sectional study is aimed at identifying age-associated plasma metabolome in a Malay population. A total of 146 (90 females) healthy participants aged 28-69 were selected for the study. Untargeted metabolomics profiling was performed using liquid chromatography-tandem mass spectrometry. Association analysis was based on the general linear model. Gender-associated metabolites were adjusted for age, while age-associated metabolites were adjusted for gender or analyzed in a gender-stratified manner. Gender-associated metabolites such as 4-hydroxyphenyllactic acid, carnitine, cortisol, and testosterone sulfate showed higher levels in males than females. Deoxycholic acid and hippuric acid were among the metabolites with a positive association with age after being adjusted for gender, while 9(E),11(E)-conjugated linoleic acid, cortisol, and nicotinamide were negatively associated with age. In gender-stratified analysis, glutamine was one of the common metabolites that showed a direct association with age in both genders, while metabolites such as 11-deoxy prostaglandin F2β, guanosine monophosphate, and testosterone sulfate were inversely associated with age in males and females. This study reveals several age-associated metabolites in Malays that could reflect the changes in metabolisms during aging and may be used to discern the risk of geriatric syndromes and disorders later. Further studies are required to determine the interplay between these metabolites and environmental factors on the functional outcomes during aging.

Host-microbe co-metabolism via MCAD generates circulating metabolites including hippuric acid

The human gut microbiota produces dozens of small molecules that circulate in blood, accumulate to comparable levels as pharmaceutical drugs, and influence host physiology. Despite the importance of these metabolites to human health and disease, the origin of most microbially-produced molecules and their fate in the host remains largely unknown. Here, we uncover a host-microbe co-metabolic pathway for generation of hippuric acid, one of the most abundant organic acids in mammalian urine. Combining stable isotope tracing with bacterial and host genetics, we demonstrate reduction of phenylalanine to phenylpropionic acid by gut bacteria; the host re-oxidizes phenylpropionic acid involving medium-chain acyl-CoA dehydrogenase (MCAD). Generation of germ-free male and female MCAD−/− mice enabled gnotobiotic colonization combined with untargeted metabolomics to identify additional microbial metabolites processed by MCAD in host circulation. Our findings uncover a host-microbe pathway for the abundant, non-toxic phenylalanine metabolite hippurate and identify β-oxidation via MCAD as a novel mechanism by which mammals metabolize microbiota-derived metabolites.

Creep Feeding and Weaning Influence the Postnatal Evolution of the Plasma Metabolome in Neonatal Piglets

Data on the evolution of blood metabolites and metabolic markers in neonatal piglets are scarce, although this information is vital to detect physiological aberrations from normal development. We aimed to characterize age- and nutrition-related changes in the plasma metabolome and serum biochemistry of suckling and newly weaned piglets and assess metabolite patterns as physiological markers for the two phases. In two replicate batches (n = 10 litters/group), piglets either received sow milk alone or were additionally offered creep feed from day 10 until weaning (day 28). Blood was collected from one piglet/litter on days 7, 14, 21, 28, 31 and 35 of life, totaling five females and five males/group/day. Signature feature ranking identified plasma triglycerides (TG) as discriminative for age and nutrition during the suckling phase. Influential TG 20:4_36:5, TG 17:0_34:2 and TG 18:2_38:6 were higher in creep-fed piglets on days 14, 21 and 28 of life, respectively, compared to only sow milk-fed piglets. Metabolites belonging to pathways within histidine, D-glutamine and D-glutamate metabolism as well as hippuric acid were distinctive for the postweaning compared to the suckling period. In conclusion, plasma lipid profiles especially corresponded to the type of nutrition in the suckling phase and showed a strong weaning effect.

Eu(III)-Functionalized MOF-Based Dual-Emission Ratiometric Sensor Integrated with Logic Gate Operation for Efficient Detection of Hippuric Acid in Urine and Serum

With the introduction of Eu3+ ions as the secondary fluorescent signal reporter and sensing active sites, a dual-emission ratiometric sensor of Eu3+@NiMOF (Eu3+ functional NiMOF) for hippuric acid (HA) detection in urine and serum was fabricated via the postsynthetic encapsulating strategy. Based on the two emission signals at 441 nm (turn-on) and 628 nm (turn-off), the produced Eu3+@NiMOF ratiometric sensor provided enhanced sensitivity, higher selectivity, and 9.7 times lower limits of detection (LOD) for the detection of HA (2.38 μM, 0.42 μg·mL-1) than that of the pristine NiMOF. Considering the high sensitivity and visualization results, further exploration of intelligent applications in the HA sensing process was carried out by constructing a tandem combinational logic gate to improve the practicability and convenience with the help of a smartphone. This work provides a promising approach for developing MOF-based ratiometric sensors to detect biomarkers.

Synthesis and Characterization of Mixed Ligand Complexes of Co(II) And Ni(II) with Hippuric Acid, Ammonium Thiocyanate and Hydroxyl Ammonium Chloride

Synthesis and Characterization of Mixed Ligand Complexes of Co(II) And Ni(II) with Hippuric Acid, Ammonium Thiocyanate and Hydroxyl Ammonium Chloride

A metabolic readout of the urine metabolome of COVID-19 patients.

Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.

Efficient Optosensing of Hippuric Acid in the Undiluted Human Urine with Hydrophilic "Turn-On"-Type Fluorescent Hollow Molecularly Imprinted Polymer Microparticles.

The development of complex biological sample-compatible fluorescent molecularly imprinted polymers (MIPs) with improved performances is highly important for their real-world bioanalytical and biomedical applications. Herein, we report on the first hydrophilic "turn-on"-type fluorescent hollow MIP microparticles capable of directly, highly selectively, and rapidly optosensing hippuric acid (HA) in the undiluted human urine samples. These fluorescent hollow MIP microparticles were readily obtained through first the synthesis of core-shell-corona-structured nitrobenzoxadiazole (NBD)-labeled hydrophilic fluorescent MIP microspheres by performing one-pot surface-initiated atom transfer radical polymerization on the preformed "living" silica particles and subsequent removal of their silica core via hydrofluoric acid etching. They showed "turn-on" fluorescence and high optosensing selectivity and sensitivity toward HA in the artificial urine (the limit of detection = 0.097 μM) as well as outstanding photostability and reusability. Particularly, they exhibited much more stable aqueous dispersion ability, significantly faster optosensing kinetics, and higher optosensing sensitivity than their solid counterparts. They were also directly used for quantifying HA in the undiluted human urine with good recoveries (96.0%-102.0%) and high accuracy (RSD ≤ 4.0%), even in the presence of several analogues of HA. Such fluorescent hollow MIP microparticles hold much promise for rapid and accurate HA detection in the clinical diagnostic field.

Art of Writing Flowchart in Organic Chemistry Practicals Induces Logical Thinking in Chemistry Students

In this article we present an art of writing flowcharts in organic chemistry preparation practicals. We divided students into two groups. One group of students was trained to write procedural flowchart and the other group of students was educated to write chemical flowchart for the preparation of p-nitroacetanilde from acetanilde and preparation of hippuric acid from glycine. The procedural flowchart simply represents the steps involved in an organic preparation. While, chemical flowchart describes chemical species involved in each step of preparation. We found that students educated to write chemical flowchart have gained superior knowledge in chemistry over the students who were trained to write procedural flowchart.

Effective extraction of the metabolites of toluene and xylene based on a postsynthetic-modified magnetic covalent organic polymer

Toluene and xylene are volatile organic compounds, and long-term exposure to toluene and xylene may cause brain structure and nervous system damage. To evaluate exposure to toluene and xylene in the environment, it is usually possible to monitor their metabolites in organisms, hippuric acid (HA) and methylhippuric acid (MHA). In this work, we designed a new magnetic solid phase extraction (MSPE) sorbent, zirconium postsynthetic-modified magnetic covalent organic polymer (Fe3O4@COP-COOZr), for purifying and enriching HA and 4-MHA. Zirconium ions were immobilized on the magnetic COP surface by postsynthetic modification without the use of additional coating layers or chelating ligands. The developed Fe3O4@COP-COOZr interacted with HA and 4-MHA through the π-π stacking effect and electrostatic interactions, as well as strong chelation with coordinatively unsaturated zirconium sites. The promising affinity material of Fe3O4@COP-COOZr in MSPE had high stability and recyclability. The established MSPE-HPLC-UV method showed low sorbent consumption (10 mg) and high sensitivity (LODs less than 0.1 μg L−1), and can be used for the analysis of HA and 4-MHA in real samples. The recoveries of the proposed method in real urine samples for the simultaneous determination of HA and 4-MHA were in the range of 83.5–103.2 %, and the RSDs were 0.9–7.1 %.

Serum organic acid metabolites can be used as potential biomarkers to identify prostatitis, benign prostatic hyperplasia, and prostate cancer.

Noninvasive methods for the early identify diagnosis of prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer (PCa) are current clinical challenges. The serum metabolites of 20 healthy individuals and patients with prostatitis, BPH, or PCa were identified using untargeted liquid chromatography-mass spectrometry (LC-MS). In addition, targeted LC-MS was used to verify the organic acid metabolites in the serum of a validation cohort. Organic acid metabolites had good sensitivity and specificity in differentiating prostatitis, BPH, and PCa. Three diagnostic models identified patients with PROSTATITIS: phenyllactic acid (area under the curve [AUC]=0.773), pyroglutamic acid (AUC=0.725), and pantothenic acid (AUC=0.721). Three diagnostic models identified BPH: citric acid (AUC=0.859), malic acid (AUC=0.820), and D-glucuronic acid (AUC=0.810). Four diagnostic models identified PCa: 3-hydroxy-3-methylglutaric acid (AUC=0.804), citric acid (AUC=0.918), malic acid (AUC=0.862), and phenyllactic acid (AUC=0.713). Two diagnostic models distinguished BPH from PCa: phenyllactic acid (AUC=0.769) and pyroglutamic acid (AUC=0.761). Three diagnostic models distinguished benign BPH from PROSTATITIS: citric acid (AUC=0.842), ethylmalonic acid (AUC=0.814), and hippuric acid (AUC=0.733). Six diagnostic models distinguished BPH from prostatitis: citric acid (AUC=0.926), pyroglutamic acid (AUC=0.864), phenyllactic acid (AUC=0.850), ethylmalonic acid (AUC=0.843), 3-hydroxy-3-methylglutaric acid (AUC=0.817), and hippuric acid (AUC=0.791). Three diagnostic models distinguished PCa patients with PROSTATITISA < 4.0 ng/mL from those with PSA > 4.0 ng/mL: 5-hydromethyl-2-furoic acid (AUC=0.749), ethylmalonic acid (AUC=0.750), and pyroglutamic acid (AUC=0.929). Conclusions: These results suggest that serum organic acid metabolites can be used as biomarkers to differentiate prostatitis, BPH, and PCa.

Easy Route to New Fused Dihydroisoquinoline-Naphthyridinone Frameworks

AbstractThe reaction of 1-methyl-3,4-dihydroisoquinolines with azlactone, obtained from hippuric acid and phthalic anhydride, provided 2-(3-benzamido-4-oxo-6,7-dihydro-4H-pyrido[2,1-a]isoquinolin-2-yl)benzoic acids, which were converted into previously unknown dihydroisoquinoline-naphthyridinones by the action of hydrazine hydrate. Further reaction of the prepared naphthyridine-5,7-diones with POCl3 under various conditions led to the formation of 5-chloro-9,10-dihydro-7H-benzo[c]isoquinolino[1,2-g][1,7]naphthyridin-7-ones or 4,6-dichloro-2-(2-(2-methylprop-1-en-1-yl)phenyl)benzo[c][1,7]naphthyridines. It was also shown that the halogen atom in the C-5 position enters into a substitution reaction with primary and secondary amines.

Comparative effects of benzoic acid and sodium benzoate in diets for nursery pigs on growth performance and acidification of digesta and urine.

The objective of this study was to evaluate the comparative effects of benzoic acid and sodium benzoate in feeds on digesta pH, urinary pH, and growth performance for nursery pigs. A total of 432 pigs (6.9 ± 0.9 kg BW) were assigned to eight treatments (6 pigs per pen, replication = 9) in a randomized complete block design with initial body weight (BW) as a block and fed for 41 d in three phases (7/17/17 d, respectively). Treatments were 1) a basal diet (NC), 2) NC + 0.25% bacitracin methylene disalicylate (antibiotic; bacitracin: 250 g/t feed; PC), 3) NC + 0.25% benzoic acid, 4) NC + 0.35% benzoic acid, 5) NC + 0.50% benzoic acid, 6) NC + 0.30% sodium benzoate, 7) NC + 0.40% sodium benzoate, and 8) NC + 0.60% sodium benzoate. Growth performance and fecal scores were measured for each phase. One gilt representing the median BW of each pen was euthanized to collect digesta from the stomach, proximal jejunum, distal jejunum, and cecum, and urine. The PC tended to improve average daily gain (ADG) in phase 1 (P = 0.052) and phase 2 (P = 0.093) as well as average daily feed intake (ADFI) in phase 2 (P = 0.052). Overall, increasing supplemental benzoic acid tended to have a quadratic effect on ADG (P = 0.094), but no difference in ADFI was observed. Increasing supplemental sodium benzoate showed a quadratic effect (P < 0.05) on ADG and linearly increased (P < 0.05) ADFI. Urinary pH linearly decreased (P < 0.05) with increasing supplemental benzoic acid, but was not affected by supplemental sodium benzoate. Increasing supplemental benzoic acid or sodium benzoate linearly increased (P < 0.05) benzoic acid content in digesta of the stomach. Increasing supplemental benzoic acid or sodium benzoate also linearly increased (P < 0.05) urinary hippuric acid. However, the PC did not decrease urinary pH or increase urinary benzoic acid and hippuric acid. With slope-ratio assay using ADG and urinary hippuric acid as dependent variables and benzoic acid intake as an independent variable, the relative bioavailability of benzoic acid compared to sodium benzoate was not different. In conclusion, supplementation of benzoic acid and sodium benzoate could improve the growth performance of nursery pigs. The relative bioavailability of sodium benzoate to benzoic acid of nursery pigs did not differ based on BW gain and urinary hippuric acid.

Monitoring the level of urinary metabolites of toluene and xylene in pregnant women in Isfahan and Khansar and their relationship with demographic factors and air quality index

Aim: In this study, the levels of urinary metabolites of toluene and xylene isomers in pregnant women in Isfahan and Khansar cities and their associations with air quality index (AQI) and demographic factors were investigated. Materials and Methods: Depending on the population, 55 pregnant women from Isfahan and 15 pregnant women from Khansar, a total of 70 people were enrolled in the study and 140 urine samples were collected during their 1st and 3rd trimesters of pregnancy (autumn and spring). Urinary metabolites of hippuric acid (HA), ortho-, meta-, and para-methyl HA (o-m-p-MHA) were extracted by dispersive liquid-liquid microextraction method, derivatized and analyzed using gas chromatography/mass spectrometer. The results were statistically correlated with AQI level and demographic factors using appropriate statistical methods. Results: Mean urinary concentrations of HA, o-m-p-MHA in the 1st trimester of pregnancy were 371.2, 1.14, 2.48, and 1.97 mg/g cr, and those in the 3rd trimester were 582.1, 3.54, 6.93, and 2.43 mg/g cr, respectively. In the 1st trimester, the mean urinary level of ortho-MHA was significantly associated with the outdoor exposure time on workdays and fragrances use (P < 0.05). In the 3rd trimester, the mean concentration of HA was significantly correlated to age and outdoor exposure time on workdays (P < 0.05). Conclusion: The mean urinary concentrations of HA and MHA isomers in the 1st trimester of pregnancy in Isfahan were more than those in Khansar. Because the level of air pollution in Isfahan was higher than Khansar and that in autumn was higher than spring. In the 3rd trimester of pregnancy, the mean levels of MHA isomers in Isfahan were more than those in Khansar. Only the amount of p-MHA was significantly associated with AQI in the 1st trimester of pregnancy. Thus, women who lived in high-traffic urban areas with high AQI were more exposed to toluene and xylene compounds.