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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 -
BMC Complementary Medicine and Therapies Feb 2022Echinacoside (ECH) possesses a wide range of biological activity. This present study analyzes the effect of ECH on cytochrome P450 isozymes (CYPs) activities of human...
BACKGROUND
Echinacoside (ECH) possesses a wide range of biological activity. This present study analyzes the effect of ECH on cytochrome P450 isozymes (CYPs) activities of human liver microsomes.
METHODS
The effect of ECH on CYPs enzyme activities were studied using the enzyme-selective substrates phenacetin (1A2), chlorzoxazone (2E1), S-mephenytoin (2C19), testosterone (3A4), coumarin (2A6), diclofenac (2C9), paclitaxel (2C8), and dextromethorphan (2D6). The IC50 values for CYP1A2, CYP2E1, CYP2C19, and CYP3A4 isoforms were examined to express the strength of inhibition. Further, the inhibition of CYPs was checked for time-dependent or not, and then fitted with competitive or non-competitive inhibition models. The corresponding parameters were also obtained.
RESULTS
ECH caused inhibitions on CYP1A2, CYP2E1, CYP2C19 and CYP3A4 enzyme activities in HLMs with IC50 of 21.23, 19.15, 8.70 and 55.42 μM, respectively. The obtained results showed that the inhibition of ECH on CYP3A4 was time-dependent with the KI/K value of 6.63/0.066 min·μM. Moreover, ECH inhibited the activity of CYP1A2 and CYP2E1 via non-competitive manners (K = 10.90 μM and K = 14.40 μM, respectively), while ECH attenuated the CYP2C19 activity via a competitive manner (K = 4.41 μM).
CONCLUSIONS
The results of this study indicate that ECH inhibits CYP1A2, CYP2E1, CYP2C19 and CYP3A4 activities in vitro. In vivo and clinical studies are warranted to verify the relevance of these interactions.
Topics: Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Glycosides; Humans; Isoenzymes
PubMed: 35180866
DOI: 10.1186/s12906-022-03517-0 -
Frontiers in Pharmacology 2022Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive,...
Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the profiles of drug absorption, distribution, metabolism, and excretion can be predicted. To evaluate the application of such an approach in preclinical investigations, the plasma pharmacokinetic profiles of seven commonly used probe substrates of microsomal enzymes, including phenacetin, tolbutamide, omeprazole, metoprolol, chlorzoxazone, nifedipine, and baicalein, were predicted in rats using bottom-up PBPK models built with data alone. The prediction's reliability was assessed by comparison with pharmacokinetic data reported in the literature. The overall predicted accuracy of PBPK models was good with most fold errors within 2, and the coefficient of determination (R) between the predicted concentration data and the observed ones was more than 0.8. Moreover, most of the observation dots were within the prediction span of the sensitivity analysis. We conclude that PBPK modeling with acceptable accuracy may be incorporated into preclinical studies to refine investigations, and PBPK modeling is a feasible strategy to practice the principles of 3Rs.
PubMed: 35645843
DOI: 10.3389/fphar.2022.895556 -
Pharmaceutics Mar 2020Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody-drug conjugates (ADCs) for cancer therapy. The effects of mertansine on uridine...
Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody-drug conjugates (ADCs) for cancer therapy. The effects of mertansine on uridine 5'-diphospho-glucuronosyltransferase (UGT) activities in human liver microsomes and its effects on the mRNA expression of cytochrome P450s (CYPs) and UGTs in human hepatocytes were evaluated to assess the potential for drug-drug interactions (DDIs). Mertansine potently inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-β-glucuronidation, and UGT1A4-catalyzed trifluoperazine -β-d-glucuronidation, with values of 13.5 µM, 4.3 µM, and 21.2 µM, respectively, but no inhibition of UGT1A6, UGT1A9, and UGT2B7 enzyme activities was observed in human liver microsomes. A 48 h treatment of mertansine (1.25-2500 nM) in human hepatocytes resulted in the dose-dependent suppression of mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, and UGT1A9, with IC values of 93.7 109.1, 36.8 18.3, 160.6 167.4, 32.1 14.9, 578.4 452.0, 539.5 233.4, 856.7 781.9, and 54.1 29.1 nM, respectively, and decreased the activities of CYP1A2-mediated phenacetin -deethylase, CYP2B6-mediated bupropion hydroxylase, and CYP3A4-mediated midazolam 1-hydroxylase. These in vitro DDI potentials of mertansine with CYP1A2, CYP2B6, CYP2C8/9/19, CYP3A4, UGT1A1, and UGT1A9 substrates suggest that it is necessary to carefully characterize the DDI potentials of ADC candidates with mertansine as a payload in the clinic.
PubMed: 32131538
DOI: 10.3390/pharmaceutics12030220 -
Forensic Science International Aug 2020The cutting agents, classified as diluents (pharmacologically inactive) or adulterants (pharmacologically active), are substances commonly used to cut drugs of abuse to...
The cutting agents, classified as diluents (pharmacologically inactive) or adulterants (pharmacologically active), are substances commonly used to cut drugs of abuse to increase profits. These substances are constantly changing over time, increasing the risks to the user's health caused by the compounds' potential individual toxicities as well as their drug-drug interactions. This work aimed to develop and validate a screening method using a portable quadrupole-based gas chromatography mass spectrometer (FLIR Griffin™ G510) to identify drugs of abuse and adulterants in seized material, and compare it with a well validated standard technology, gas chromatography mass spectrometry (GC-MS). The method was validated for the identification of alprazolam, amphetamine, aminopyrine, benzocaine, caffeine, cocaine, codeine, diltiazem, ephedrine, fentanyl, fenethylline, furanylfentanyl, heroin, hydroxyzine, levamisole, lidocaine, methamphetamine, morphine, noramidopyrine (a marker of metamizole), phencyclidine, phenacetin, procaine, strychnine and xylazine. The targeted substances were chosen based on current intelligence regarding prevalent adulterants observed in multiple jurisdictions. Interference, precision, robustness and carryover were evaluated. The method was successfully validated and proved to be suitable to detect and identify the 24 target compounds proposed. The reliability of the instrument for detecting the presence of targeted compounds was analyzed by using Receiver Operating Characteristic (ROC) analysis. The portable quadrupole-based gas chromatography mass spectrometer was considered suitable for use in forensic analysis as a screening method.
Topics: Drug Contamination; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Illicit Drugs; Limit of Detection; Reproducibility of Results
PubMed: 32474342
DOI: 10.1016/j.forsciint.2020.110342 -
Beijing Da Xue Xue Bao. Yi Xue Ban =... Apr 2024The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early... (Comparative Study)
Comparative Study
OBJECTIVE
The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early stage of autologous tendon reconstruction of the anterior cruciate ligament (ACL) of the knee joint were compared.
METHODS
Retrospective analysis of postoperative pain and drug analgesia in 45 patients performed by the same group from November 2018 to February 2019. The random area group design was divided into two groups according to whether ACL rupture was combined with meniscal injury, group A was 24 patients with ACL reconstruction of knee joint and group B was 21 patients with ACL fracture combined with meniscus injury. The two groups were divided into three subgroups respectively according to the actual treatment of postoperative analgesic drugs received by the patients, including 4 cases of compound aminopyrine phenacetin tablets, 11 cases of oral tramcontin, 9 cases of intramuscular dolantin combined with phenergan in group A; 3 cases of compound aminopyrine phenacetin tablets, 10 cases of oral tramcontin, and 8 cases of intramuscular dolantin combined with phenergan in group B. When the early postoperative patients complain about pain and actively ask for analgesia. When the patients complained about pain after the operation and actively asked for analgesia, they were randomly given painkillers, tramcontin or dolantin combined with phenergan to relieve pain. Pain visual analogue scale (VAS) was used to evaluate pain relief and observe the occurrence of adverse reactions.
RESULTS
There were no significant dif-ferences in gender, age, body mass index, and time of hospital stay between the two groups of patients ( > 0.05). In the patients who used tramcontin and dolantin combined with phenergan to relieve pain judging by VAS score before and 1 h after taking the drug, it was found that the pain situation of the patient was significantly relieved, and the difference before and after taking the drug had statistical significance ( < 0.05). Pairwise comparisons of the three drugs applied in the two groups showed significantly greater pain relief in the dolantin combined with phenergan group than in the remaining two drugs. There was no significant difference ( > 0.05). Dolantin was prone to nausea and vomiting, but the application of phenergan was also used to reduce side effects. In terms of adverse reactions, only 1 case of nausea occurred in the tramcontin group for simple ACL reconstruction, and none of the patients in the other groups showed serious complications and allergic reactions.
CONCLUSION
Whether in cruciate ligament reconstruction alone or combined with meniscus molding or suture, compound aminopyrine phenacetin tablets, tramcontin, dolantin combined with phenergan can effectively relieve pain. Among the three drugs, dolantin caused the largest pain relief. At the same time, the combination of phenergan effectively reduced the adverse reactions, such as vomiting and nausea, and increased the drug safety.
Topics: Humans; Aminopyrine; Analgesics; Anterior Cruciate Ligament Injuries; Anterior Cruciate Ligament Reconstruction; Knee Joint; Meperidine; Nausea; Pain, Postoperative; Phenacetin; Promethazine; Retrospective Studies; Treatment Outcome; Vomiting
PubMed: 38595247
DOI: 10.19723/j.issn.1671-167X.2024.02.014 -
Chemistry, An Asian Journal Mar 2022SnO -CNF was prepared by coaxial blending technology, and MoS was grown uniformly on SnO -CNF composite by adding a hydrothermal post-treatment step. The uniform...
SnO -CNF was prepared by coaxial blending technology, and MoS was grown uniformly on SnO -CNF composite by adding a hydrothermal post-treatment step. The uniform distribution of MoS on one-dimensional SnO -CNF can effectively establish a layered three-dimensional structure. Accordingly, the prepared MoS -coated SnO -CNF composite material has higher surface area and more active sites to obtain better electrochemical performance. We constructed an electrochemical sensor within the composite material with enhanced performance to realize the simultaneous and highly sensitive detection of phenacetin and indomethacin. The sensor has linear ranges of 0.050-7200 μM and 0.05-500 μM, respectively, and the detection limits were 0.016 μM and 0.013 μM. Furthermore, the sensor has good anti-interference ability and stability, which also achieves good recovery rate in the actual sample detection.
Topics: Carbon; Electrochemical Techniques; Indomethacin; Molybdenum; Nanofibers; Phenacetin
PubMed: 35018742
DOI: 10.1002/asia.202101372 -
The Science of the Total Environment Jul 2024Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its...
Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.
Topics: Nitrification; Waste Disposal, Fluid; Phenacetin; Wastewater; Drug Resistance, Microbial; Water Pollutants, Chemical; Bacteria
PubMed: 38744392
DOI: 10.1016/j.scitotenv.2024.173190 -
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 -
Journal of Molecular Modeling Sep 2020Spectroscopic analysis and different quantum mechanical studies of four pharmaceutically active compounds phenacetin, p-acetanisidide, 4'-butoxyacetanilide, and...
Spectroscopic analysis and different quantum mechanical studies of four pharmaceutically active compounds phenacetin, p-acetanisidide, 4'-butoxyacetanilide, and 4'-(3-chloropropoxy)acetanilide are reported in this manuscript. Simulated IR spectrum of these compounds was compared with experimentally available data, and essential functional group assignments were made. We also report the frontier orbital properties and other derived local energy descriptors which talks about the relative stability and reactivity. Photovoltaic efficiency of the compounds was studied from the simulated electronic spectra. The compound was found to interact with graphene and fullerene, to form molecular self-assembly. These self-assemblies showed tremendous enhancement in various physicochemical properties when compared with its constituents. The nature of the interactions between studied chemical species was discussed with the help of chemical reactivity principles. Biological activity of the compounds was predicted using molecular docking studies. It is interesting to see that on adsorption with a graphene/fullerene surface, all adsorbed complex shows enhancement in the Raman activity giving surface enhanced Raman spectra (SERS). This can be used for the detection of these drugs in a pharmacological or biological sample. Interestingly the graphene/fullerene drug molecular assembly shows enhanced biological activity when compared with individual drug molecules. Graphical abstract.
PubMed: 32876867
DOI: 10.1007/s00894-020-04485-3