Rewiring cis-2-butene-1,4-dial mediated urinary metabolomics fingerprints of short-term exposure to furan.

Furan represents one of the dietary-sourced persistent organic pollutants and thermal processing contaminants. Given its widespread occurrence in food and various toxicological effects, accurately assessing furan exposure is essential for informing public health risks. Furan is metabolized to a reactive primary product, cis-2-butene-1,4-dial (BDA) upon absorption. Some of the resulting BDA-derived metabolites have been proposed as potential exposure biomarkers of furan. However, the lack of quantification for recognized and feasible furan biomarkers has hampered the development of internal exposure risk assessment of furan. In this study, we employed reliable non-targeted metabolomics techniques to uncover urinary furan metabolites and elucidate their chemical structures. We characterized 8 reported and 11 new furan metabolites derived from the binding of BDA with glutathione (GSH), biogenic amines, and/or amino acids in the urine of male rats subjected to varying doses of furan. Notably, a mono-GSH-BDA adduct named cyclic GSH-BDA emerged as a highly prospective specific biomarker of furan exposure, as determined by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method. Cyclic GSH-BDA demonstrated a robust mass spectrometry ion response intensity and exhibited evident time- and dose response. Additionally, we conducted a comprehensive profiling of the kinetics of potential furan biomarkers over time to capture the metabolic dynamics of furan in vivo. Most urinary furan metabolites reached peak concentrations at either the first (3 h) or second (6 h) sampling time point and were largely eliminated within 36 h following furan treatment. The present study provides novel insights into furan metabolism and sheds light on the biomonitoring of furan exposure.

Assessing human exposure to phthalate esters in drinking water migrated from various pipe materials and water filter elements during water treatments and storage.

Plastic water-supply pipes and filter element are frequently used in municipal water supply systems. Leaching of phthalate esters (PAEs) from these pipes and filter elements to drinking water has become a common concern among the public. In this study, the migrations of 16 phthalate esters (PAEs) in seven different kinds of water-supply product materials were investigated. Di-n-butyl phthalate (DBP) had the highest detection frequency of 54.4% in the water leaching samples of various water supply pipes and water filter elements samples, followed by Diisobutyl phthalate (DIBP, 46/90, 51.1%). The maximum detected concentration level for di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate (DEP), and DBP in the leaching experiment was below the regulatory limit values of 8 µg/L, 300 µg/L, and 3 µg/L for each compound in China standards for drinking water quality. The increasing of the water temperature, the lower pH of the water, and the increasing of the leaching time will increase the migration of PAEs from plastic pipes into water. The chronic daily intake of children aged < 1-12 years to PAEs through drinking water was higher than the rest of the population groups. Carcinogenic risks (CR) of DEHP via drinking water were neglectable for most groups of people, while for young children with age of 1-2 years old, the CR is an acceptable risk.

Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND Compound porcine cerebroside and ganglioside injection (CPCGI) has been widely applied in clinical practice in China to treat functional confusion caused by brain diseases. Sevoflurane, a frequently-used inhalational anesthetic, was discovered to have neurotoxicity that can cause neurological damage in patients. The present study was performed to investigate the protective effect of CPCGI on sevoflurane-induced nerve damage and to reveal the neuroprotective mechanisms of CPCGI. MATERIAL AND METHODS Firstly, the hippocampal neurons were separated from Sprague-Dawley embryonic rats, and were stimulated by 3% sevoflurane for different times (0, 2, 4, and 6 h). Then, cell viability and cell apoptosis were assessed by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry (FCM), respectively. Western blot analysis was used to determine the apoptosis-related protein expression levels. RESULTS The results demonstrated that 3% sevoflurane significantly inhibited cell viability but induced cell apoptosis in neurons in a time-dependent manner. Treatment with 3% sevoflurane also promoted the Bax (B cell leukemia/lymphoma 2​ (Bcl2)-associated X protein) and cleaved caspase3 protein expressions, and suppressed Bcl-2 and pro-caspase3 expressions in hippocampal neurons. In addition, phosphorylated (p)-p38 and p-p65 expression and the ratio of p-p38/p38 and p-p65/p65 were upregulated in a time-dependent manner after 3% sevoflurane treatment. Further analysis indicated that all the effects of 3% sevoflurane on hippocampal neurons were reversed by CPCGI pre-treatment. CONCLUSIONS We demonstrated the neuroprotective role of CPCGI in sevoflurane-stimulated neuronal cell damage via regulation of the MAPK/NF-kappaB signaling pathway.

Detection of 20 phthalate esters in breast milk by GC-MS/MS using QuEChERS extraction method.

A detection method for 20 different phthalate esters (PAEs) in breast milk analyzed by quick, easy, cheap, effective, rugged, and safe (QuEChERS) clean-up with five internal standards and quantitative GC-MS/MS was established. This method can effectively remove interfering substances such as lipids and fatty acids from breast milk using acetonitrile as the extraction solvent and PSA/C18 as clean-up materials. The 20 PAEs had a linear range of 5.0-500.0 µg/L and recoveries of 83.3-123.3% with RSDs of 0.2-7.6% (n = 6). The method detection limits (LODs) were 0.004-1.3 µg/kg. Dimethyl phthalate (DMP), Diethyl phthalate (DEP), Diisobutyl phthalate (DIBP), Di-n-butyl phthalate (DBP) and bis(2-ethylhexyl) phthalate (DEHP) were detected in the 35 breast milk samples, with median levels of 1.2, 6.8, 7.3, 32.9 and 13.6 µg/kg, respectively, and the concentrations of 20 PAEs ranged between 0.5 and 137.3 µg/kg. This is a fast, simple, sensitive and accurate method for the detection of 20 PAEs in breast milk or dairy products.

Analysis of Numerous Androgen Disruptors in Fish by Gas Chromatography Tandem Mass Spectrometry.

An improved analytical method was developed for the simultaneous quantification of numerous androgen disruptors-vinclozolin, dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes, chlordane, heptachlor, dieldrin, endrin, and aldrin-in fish, followed by GC with tandem MS (MS/MS). Extraction, cleanup, and MS/MS parameters of analytes were optimized. The LOQs of the analytes ranged from 0.3 to 3.7 µg/kg. Reasonable recoveries (73.7-119.2%) were demonstrated at different spike levels with RSDs lower than 12.2%. This method was applied for the analysis of the target analytes in fish samples sold in Hangzhou, China, and DDTs were found to be the predominant contaminants in fish samples.

Simultaneous determination of 3-monochloropropane-1,2-diol and acrylamide in food by gas chromatography-triple quadrupole mass spectrometry with coupled column separation.

Both 3-monochloropropane-1,2-diol (3-MCPD) and acrylamide are contaminants found in heat-processed foods and their related products. A quantitative method was developed for the simultaneous determination of both contaminants in food by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS). The analytes were purified and extracted by the matrix solid-phase dispersion extraction (MSPDE) technique with Extrelut NT. A coupled column (a 3 m Innowax combined with a 30 m DB-5 ms) was developed to separate both compounds efficiently without derivatization. Triple quadrupole mass spectrometry in multiple reaction monitoring mode (MRM) was applied to suppress matrix interference and obtain good sensitivity in the determination of both analytes. The limit of detection (LOD) in the sample matrix was 5 µg kg(-1) for 3-MCPD or acrylamide. The average recoveries for 3-MCPD and acrylamide in different food matrices were 90.5-107% and 81.9-95.7%, respectively, with the intraday relative standard deviations (RSDs) of 5.6-13.5% and 5.3-13.4%, respectively. The interday RSDs were 6.1-12.6% for 3-MCPD and were 5.0-12.8% for acrylamide. Both contaminants were found in samples of bread, fried chips, fried instant noodles, soy sauce, and instant noodle flavoring. Neither 3-MCPD nor acrylamide was detected in the samples of dairy products (solid or liquid samples) and non-fried instant noodles.

[Simultaneous determination of ethyl carbamate and chloropropanols in flavorings by gas chromatography-triple quadrupole tandem mass spectrometry].

A simultaneous determination method for ethyl carbamate (EC) and chloropropanols (3-monochloropropane-1, 2-diol (3-MCPD) and 2-monochloropropane-1, 3-diol (2-MCPD)) in flavorings was developed by gas chromatography-triple quadrupole tandem mass spectrometry (GC-MS/MS). After spiked with internal standard, the sample was extracted by matrix solid-phase dispersion extraction technique with an Extrelut NT column. Hexane was used to wash the fat soluble matrix interferences and then an ethyl acetate-ethyl ether (20: 80, v/v) mixture was added to elute the analytes. The concentrated extract was detected by GC-MS/MS in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) were 2, 5 and 5 microg/kg for EC, 3-MCPD and 2-MCPD, respectively. The linear ranges were 5 - 1 000 microg/kg (r = 0.9997), 10-1000 microg/kg (r = 0.999 1) and 10-1000 microg/kg (r = 0.999 5) for EC, 3-MCPD and 2-MCPD, respectively. In soy sauce, yellow rice wine, salami sauce and flavoring of instant noodle matrices, the recoveries (RSDs, n = 7) in MRM mode at the levels of 20, 100 and 400 microg/kg were 87.7%-104% (4.3%-10.7%), 90.1%-109% (2.6%-10.2%), and 90.9%-103% (3.0%-9.5%), respectively. EC, 3-MCPD and 2-MCPD were found in some real samples of the soy sauce, wine and flavoring of instant noodle. EC or 3-MCPD was found in some of the salami samples. The method is accurate, fast and suitable for the simultaneous determination of EC, 3-MCPD and 2-MCPD in flavorings.