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Huan Jing Ke Xue= Huanjing Kexue Apr 2023Ozonation has gradually become a routine process for advanced wastewater treatment. During the technology innovation on the advanced treatment of wastewater by...
Ozonation has gradually become a routine process for advanced wastewater treatment. During the technology innovation on the advanced treatment of wastewater by ozonation, researchers have to assess the performance of abundant new technologies, new reactors, and new materials. However, they are usually puzzled by the rational selection of model pollutants to assess the capability of such new technologies to eliminate the chemical oxygen demand (COD) and total organic carbon (TOC) of practical wastewater. It is unclear how well the various model pollutants reported in the literature could represent the COD/TOC removal of actual wastewater. The rational selection and evaluation of model pollutants for advanced treatment of industrial wastewater is of great significance in establishing the technological standard system for advanced treatment of wastewater via ozonation. Herein, the aqueous solutions (including unbuffered solutions and bicarbonate-buffered solutions) of 19 model pollutants and four practical secondary effluents from industrial parks were investigated through ozonation under identical conditions. The similarity in COD/TOC removal of the above wastewater/solutions were evaluated using mainly clustering analysis. The results showed that the dissimilarity among the model pollutants was greater than that among the actual wastewaters, thus enabling the rational selection of several model pollutants to assess the performance of advanced treatment of wastewater using ozonation by different technologies. The errors of predicting the COD removal of secondary sedimentation tank effluent by ozonation in 60 min using the unbuffered aqueous solutions of ketoprofen (KTP), dichlorophenoxyacetic acid (2,4-D), and sulfamethazine (SMT) were less than 9%, and those using the bicarbonate-buffered solutions of phenacetin (PNT), SMT, and sucralose were less than 5%. The evolution of pH by using the bicarbonate-buffered solutions was more similar to that in practical wastewater than by using unbuffered aqueous solutions. In the similarity evaluation of COD/TOC removal between the bicarbonate-buffered solutions and the practical wastewaters, the results were almost the same whether considering different input ozone concentration conditions. Therefore, the protocol proposed in this study based on similarity evaluation to assess the performance treating actual wastewater could be extended to different ozone concentration conditions with certain universality.
PubMed: 37040966
DOI: 10.13227/j.hjkx.202205124 -
Frontiers in Pediatrics 2023drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been...
drug exposure is a significant public health threat to the well-being and normal development of the neonate. Recently, testing of umbilical cord tissue (UCT) has been employed to measure illicit drug exposure, as drugs used by the mother during the third trimester may be retained in the UCT. Focus has also been given to potential adverse health effects among drug users, resulting from exposure to pharmacologically active adulterants and cutting agents in the street drug supply. The effects of these substances have not been well studied in humans, nor has their presence been demonstrated as a means for assessing adverse health effects in the neonate. Here, we describe the application of a novel test method to analyze UCT for the presence of more than 20 common adulterating/cutting substances via LC/Q-TOF. In total, 300 de-identified UCT samples were analyzed-all had previously tested positive for cocaine or opiates. Generally, the positivity rates of individual compounds were similar between the Cocaine and Opiates Subgroups, apart from levamisole, xylazine, dipyrone (metabolites), and promethazine. Many of the adulterants used in the street drug supply do have legitimate medicinal/therapeutic uses, including several of the compounds most frequently detected in this study. Caffeine and lidocaine were the most frequently identified compounds both individually (>70% each) and in combination with each other. Alternatively, levamisole, an adulterant with no legitimate therapeutic use, was present in 12% of cases. Importantly, this data demonstrates that the detection of traditional drugs of abuse may serve as indicators of potential exposure to toxic adulterating substances during gestation. While there is cause for concern with respect to any unintentional drug exposure, illicit drug use during pregnancy, including uncontrolled dosing, poly-adulterant consumption, and the interactions of these drug mixtures, produces a significant public health threat to the neonate which warrants further study.
PubMed: 37025298
DOI: 10.3389/fped.2023.1127020 -
Molecules (Basel, Switzerland) Jan 2023Benzisothiazolinone (BIT), a biocide widely used as a preservative in household cleaning and personal care products, is cytotoxic to lung cells and a known skin allergen...
Benzisothiazolinone (BIT), a biocide widely used as a preservative in household cleaning and personal care products, is cytotoxic to lung cells and a known skin allergen in humans, which highlights the importance of assessing its toxicity and pharmacokinetics. In this study, a simple, sensitive, and accurate LC−MS/MS method for the quantification of BIT in rat plasma, urine, or tissue homogenates (50 μL) using phenacetin as an internal standard was developed and validated. Samples were extracted with ethyl acetate and separated using a Kinetex phenyl−hexyl column (100 × 2.1 mm, 2.6 μm) with isocratic 0.1% formic acid in methanol and distilled water over a run time of 6 min. Positive electrospray ionization with multiple reaction monitoring transitions of m/z 152.2 > 134.1 for BIT and 180.2 > 110.1 for phenacetin was used for quantification. This assay achieved good linearity in the calibration ranges of 2−2000 ng/mL (plasma and urine) and 10−1000 ng/mL (tissue homogenates), with r ≥ 0.9929. All validation parameters met the acceptance criteria. BIT pharmacokinetics was evaluated via an intravenous and dermal application. This is the first study that evaluated BIT pharmacokinetics in rats, providing insights into the relationship between BIT exposure and toxicity and a basis for future risk assessment studies in humans.
Topics: Humans; Rats; Animals; Chromatography, Liquid; Tandem Mass Spectrometry; Disinfectants; Phenacetin; Reproducibility of Results
PubMed: 36677902
DOI: 10.3390/molecules28020845 -
Drug Metabolism and Disposition: the... May 2023The tree shrew, a non-rodent primate-like species, is used in various fields of biomedical research, including hepatitis virus infection, myopia, depression, and...
The tree shrew, a non-rodent primate-like species, is used in various fields of biomedical research, including hepatitis virus infection, myopia, depression, and toxicology. Recent genome analysis found that the numbers of cytochrome P450 (P450 or ) genes are similar in tree shrews and humans and their sequence identities are high. Although the P450s are a family of important drug-metabolizing enzymes, they have not yet been fully investigated in tree shrews. In the current study, tree shrew CYP2A13 cDNA was isolated from liver, and its characteristics were compared with those of pig, dog, and human CYP2As. Tree shrew CYP2A13 amino acid sequences were highly identical (87-92%) to the human CYP2As and contained sequence motifs characteristic of P450s. Phylogenetic analysis revealed that tree shrew CYP2A13 was more closely related to human CYP2As than to rat CYP2As, similar to dog and pig CYP2As. Among the tissue types analyzed, tree shrew CYP2A13 mRNA was preferentially expressed in liver and lung, similar to dog CYP2A13 mRNA, whereas dog CYP2A25 and pig CYP2A19 mRNAs were predominantly expressed in liver. Tree shrew liver microsomes and tree shrew CYP2A13 proteins heterologously expressed in Escherichia coli catalyzed coumarin 7-hydroxylation and phenacetin -deethylation, just as human, dog, and pig CYP2A proteins and liver microsomes do. These results demonstrate that tree shrew is expressed in liver and lung and encodes a functional drug-metabolizing enzyme. SIGNIFICANCE STATEMENT: Novel tree shrew cytochrome P450 2A13 (CYP2A13) was identified and characterized in comparison with human, dog, and pig CYP2As. Tree shrew CYP2A13 isolated from liver had high sequence identities and close phylogenetic relationships to its human homologs and was abundantly expressed in liver and lung at the mRNA level. Tree shrew CYP2A13 metabolized coumarin and phenacetin, human selective CYP2A6 and CYP2A13 substrates, respectively, similar to dog and pig CYP2As, and is a functional drug-metabolizing enzyme likely responsible for drug clearances.
Topics: Animals; Dogs; Humans; Rats; Cytochrome P-450 CYP2A6; Cytochrome P-450 Enzyme System; Liver; Lung; Phenacetin; Phylogeny; RNA, Messenger; Swine; Tupaia
PubMed: 36669854
DOI: 10.1124/dmd.122.001152 -
Drug Metabolism and Disposition: the... Apr 2023The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the...
The metabolism of exogenous substances is affected by the gut microbiota, and the relationship between them has become a hot topic. However, the mechanisms by which the microbiota regulates drug metabolism have not been clearly defined. This study characterizes the expression profiles of host drug-processing genes (DPGs) in antibiotics-treated rats by using an unbias quantitative RNA-sequencing method and investigates the effects of antibiotics-induced depletion of rat microbiota on the pharmacokinetic behaviors of cytochrome P450s (CYPs) probe drugs, and bile acids metabolism by ultra-performance liquid chromatography-tandem mass spectrometry. Our results show that antibiotics treatments altered the mRNA expressions of 112 DPGs in the liver and jejunum of rats. The mRNA levels of , , , , , and of CYP family members were significantly downregulated in antibiotics-treated rats. Furthermore, antibiotics treatments also resulted in a significant decrease in the protein expressions and enzyme activities of and in rat liver. Pharmacokinetic results showed that, except for tolbutamide, antibiotics treatments significantly altered the pharmacokinetic behaviors of phenacetin, omeprazole, metoprolol, chlorzoxazone, and midazolam. In conclusion, the presence of stable, complex, and diverse gut microbiota plays a significant role in regulating the expression of host DPGs, which could contribute to some individual differences in pharmacokinetics. SIGNIFICANCE STATEMENT: This study investigated how the depletion of rat microbiota by antibiotics treatments influences the expression profiles of host DPGs and the pharmacokinetic behaviors of CYPs probe drugs. Combined with previous studies in germ-free mice, this study will improve the understanding of the role of gut microbiota in drug metabolism and contribute to the understanding of individual differences in the pharmacokinetics of some drugs.
Topics: Rats; Animals; Mice; Cytochrome P-450 CYP2E1; Anti-Bacterial Agents; Rats, Sprague-Dawley; Cytochrome P-450 Enzyme System; Microbiota; RNA, Messenger
PubMed: 36623881
DOI: 10.1124/dmd.122.001173 -
Pharmaceutics Dec 2022The solubility of active pharmaceutical ingredients is a mandatory physicochemical characteristic in pharmaceutical practice. However, the number of potential solvents...
Solubility Characteristics of Acetaminophen and Phenacetin in Binary Mixtures of Aqueous Organic Solvents: Experimental and Deep Machine Learning Screening of Green Dissolution Media.
The solubility of active pharmaceutical ingredients is a mandatory physicochemical characteristic in pharmaceutical practice. However, the number of potential solvents and their mixtures prevents direct measurements of all possible combinations for finding environmentally friendly, operational and cost-effective solubilizers. That is why support from theoretical screening seems to be valuable. Here, a collection of acetaminophen and phenacetin solubility data in neat and binary solvent mixtures was used for the development of a nonlinear deep machine learning model using new intuitive molecular descriptors derived from COSMO-RS computations. The literature dataset was augmented with results of new measurements in aqueous binary mixtures of 4-formylmorpholine, DMSO and DMF. The solubility values back-computed with the developed ensemble of neural networks are in perfect agreement with the experimental data, which enables the extensive screening of many combinations of solvents not studied experimentally within the applicability domain of the trained model. The final predictions were presented not only in the form of the set of optimal hyperparameters but also in a more intuitive way by the set of parameters of the Jouyban-Acree equation often used in the co-solvency domain. This new and effective approach is easily extendible to other systems, enabling the fast and reliable selection of candidates for new solvents and directing the experimental solubility screening of active pharmaceutical ingredients.
PubMed: 36559321
DOI: 10.3390/pharmaceutics14122828 -
Pharmaceutics Dec 2022Obtusifolin, a major anthraquinone component present in the seeds of Cassia tora, exhibits several biological activities, including the amelioration of memory...
Obtusifolin, a major anthraquinone component present in the seeds of Cassia tora, exhibits several biological activities, including the amelioration of memory impairment, prevention of breast cancer metastasis, and reduction of cartilage damage in osteoarthritis. We aimed to evaluate the inhibitory effects of obtusifolin and its analogs on CYP1A enzymes, which are responsible for activating procarcinogens, and investigate its inhibitory mechanism and chemopreventive effects. P450-selective substrates were incubated with human liver microsomes (HLMs) or recombinant CYP1A1 and CYP1A2 in the presence of obtusifolin and its four analogs. After incubation, the samples were analyzed using liquid chromatography-tandem mass spectrometry. Molecular docking simulations were performed using the crystal structure of CYP1A2 to identify the critical interactions between anthraquinones and human CYP1A2. Obtusifolin potently and selectively inhibited CYP1A2-mediated phenacetin O-deethylation (POD) with a Ki value of 0.031 µM in a competitive inhibitory manner in HLMs, whereas it exhibited negligible inhibitory effect against other P450s (IC50 > 28.6 µM). Obtusifolin also inhibited CYP1A1- and CYP1A2-mediated POD and ethoxyresorufin O-deethylation with IC50 values of <0.57 µM when using recombinant enzymes. Our molecular docking models suggested that the high CYP1A2 inhibitory activity of obtusifolin may be attributed to the combination of hydrophobic interactions and hydrogen bonding. This is the first report of selective and potent inhibitory effects of obtusifolin against CYP1A, indicating their potential chemopreventive effects.
PubMed: 36559174
DOI: 10.3390/pharmaceutics14122683 -
Journal of Pharmaceutical and... Feb 2023In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic...
In this study, we investigated the effect of type 1 diabetes mellitus on the modulation of the activities of CYP450s in dynamics by a UHPLC-MS/MS method. The diabetic rat model was constructed by an intraperitoneal single injection of streptozotocin. Fasting blood glucose levels > 16.7 mmol/L were considered as diabetic. The rats were given a cocktail of four probe drugs (10 mg/kg phenacetin, 1 mg/kg tolbutamide, 10 mg/kg metoprolol, and 10 mg/kg midazolam) by oral administration for the pharmacokinetic study. Thereafter, the metabolic ratio (MR) of the metabolites to probe substrates were determined. The results indicated that two weeks after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin (CYP1A2) and 4-hydroxyl tolbutamide/tolbutamide (CYP2C9); however, it decreased the MRs of α-hydroxy metoprolol/metoprolol (CYP2D6) and 1-hydroxy midazolam/midazolam (CYP3A4). Two months after diabetes was induced, diabetes increased the MRs of acetaminophen/phenacetin and 4-hydroxyl tolbutamide/tolbutamide. The MR of α-hydroxy metoprolol/metoprolol was decreased and the MR of 1-hydroxy midazolam/midazolam was increased but the difference was not significant. According to the results, CYP1A2 and CYP2C9 activities were enhanced in the diabetic rats. and CYP2D6 activity was inhibited in a short period of diabetes; however, the decrease in CYP2D6 activity was not significant in the long period. CYP3A4 activity was decreased in a short period of diabetes and increased in a long period of diabetes but was not significant in the two periods. This study suggests the activity change rule of the CYP450 enzyme system in diabetes mellitus, which can provide a reference for precise clinical medication.
Topics: Animals; Rats; Acetaminophen; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Diabetes Mellitus, Experimental; Metoprolol; Midazolam; Phenacetin; Tandem Mass Spectrometry; Tolbutamide
PubMed: 36512868
DOI: 10.1016/j.jpba.2022.115191 -
Current Drug Metabolism Dec 2022The use of herbal medicines has tremendously increased over the past few decades. Case reports and controlled clinical investigations of herbal-drug interactions have...
BACKGROUND
The use of herbal medicines has tremendously increased over the past few decades. Case reports and controlled clinical investigations of herbal-drug interactions have been reported. Since Cytochrome P450 (CYP) enzymes play an important role in drug interactions. The evaluation of the influence of herbal medicines on the activities of CYPs is beneficial to promote scientific and rational clinical use of herbal medicines.
OBJECTIVE
Herein, we aimed to develop and validate a method to simultaneously quantify seven CYP cocktail probe drugs consisting of phenacetin (PNC), bupropion (BPP), losartan potassium (LK), omeprazole (OMP), dextromethorphan (DM), chlorzoxazone (CZZ) and midazolam (MDZ) and their respective metabolites in a single acquisition run and use this method to evaluate the influence of Zhuanggu Guanjie Pill (ZGGJP) on seven CYPs.
METHODS
A cost-effective and simple UHPLC-(±)ESI-MS/MS method for simultaneous determination of seven probe drugs and metabolites in rat plasma was developed and validated. Male and female rats were randomly divided into three groups and treated with 1.2 g/kg/d ZGGJP, 5 g/kg/d ZGGJP and 0.5% CMC-Na for 14 consecutive days. After 24 h of the last administration, all rats were administrated orally with probe drugs. The influence of ZGGJP on the CYPs was carried out by comparing the metabolic ratio (Cmax, AUC0-t) of metabolites/probe drugs in rats.
RESULTS
The calibration curves were linear, with correlation coefficient > 0.99 for seven probe drugs and their corresponding metabolites. Intra- and inter-day precisions were not greater than 15% RSD and the accuracies were within ±15% of nominal concentrations. The ZGGJP showed significant inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats.
CONCLUSION
ZGGJP had inductive effects on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats.
PubMed: 36503399
DOI: 10.2174/1389200224666221209154002 -
Journal of Environmental Management Feb 2023Chitosan, as a bio-friendly and abundant biochar precursor, was employed to prepare cobalt-based catalyst (CoO@BCC) by calcination for activating peroxymonosulfate (PMS)...
Chitosan, as a bio-friendly and abundant biochar precursor, was employed to prepare cobalt-based catalyst (CoO@BCC) by calcination for activating peroxymonosulfate (PMS) to degrade phenacetin (PNT). Various characterization technologies and experimental designs were performed to investigate the physicochemical properties and catalytic performance of CoO@BCC. Approximately 99.0% of phenacetin (10 mg/L) was degraded in the system of CoO@BCC (0.05 g/L)/PMS (1.0 mM) within 15 min and the rate constant was 6 times higher than that in the system of CoO (0.05 g/L)/PMS (1.0 mM). The results demonstrated that BCC as a carrier not only dispersed CoO nanoparticles and improved the stability of catalyst, but also provided abundant electron-rich groups to facilitate the activation of PMS and the production of reactive oxygen species (ROS). CoO@BCC composite also exhibited good universality and reusability. More than 90% of BPA, SIZ and CAP was degraded by CoO@BCC activated PMS within 15 min at pH 7. The degradation rate of PNT was recovered from 90% to 98.0% via the regeneration of the used catalyst after the third run (calcination at 400 °C for 5 min). SO, •OH and O were identified to be responsible for PNT degradation. Furthermore, the activation mechanism of PMS and the possible pathways of PNT degradation were reasonably speculated according to the results of electron paramagnetic resonance (EPR), X-ray photoelectron spectroscopy (XPS), quenching experiments and HPLC-TOF-MS. This study explored the application of chitosan as a recycled material and provides a feasible strategy for designing and fabricating environmentally friendly and efficient catalysts for PMS activation to degrade organic pollutants.
Topics: Phenacetin; Chitosan; Peroxides
PubMed: 36463841
DOI: 10.1016/j.jenvman.2022.116895