Enantioselective toxicity effect and mechanisms of bifenthrin enantiomers on normal human hepatocytes.

In recent decades, the toxicity of chiral pesticides to non-target organisms has attracted increasing attention. Cellular metabolic disorders are essential sensitive molecular initiating event for toxicological effects. BF is a typical chiral pesticide, and the liver is the main organ for BF accumulation. This study aimed to investigate the potential molecular mechanism of BF enantiomers' different toxic effects on L02 by a non-targeted metabolomic approach. Results revealed that the BF enantiomers exhibited different metabolic responses. In total, 51 and 36 differential metabolites were perturbed by 1S-cis-BF and 1R-cis-BF at the value of variable importance, respectively. When L02 were exposed to 1R-cis-BF, the significantly disturbed metabolic pathways were nicotinate and nicotinamide metabolism and pyrimidine metabolism. By comparison, more significantly perturbed metabolic pathways were received when the L02 were exposed to 1S-cis-BF, including glycine, serine and threonine metabolism, nicotinate and nicotinamide metabolism, arginine and proline metabolism, cysteine and methionine metabolism, glycerolipid metabolism, histidine metabolism, pyrimidine metabolism, amino sugar and nucleotide sugar metabolism and arginine biosynthesis. The results offer a new perspective in understanding the role of selective cytotoxicity of BF enantiomers, and help to evaluate the risk to human health at the enantiomeric level.

Simultaneous determination of five constituents of areca nut extract in rat plasma using UPLC-MS/MS and its application in a pharmacokinetic study.

Areca nuts have been used as a traditional Chinese medicine (TCM) for thousands of years. Recent studies have shown that it exhibits good pharmacological activity and toxicity. In this study, the pharmacokinetics of five major components of areca nut extract in rats were investigated using a highly sensitive ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC-MS/MS) method. Arecoline, arecaidine, guvacoline, guvacine, and catechin were separated and quantified accurately using gradient elution with mobile phases of (A) water containing 0.1 % formic acid-10 mM ammonium formate, and (B) methanol. The constituents were detected under a timing switch between the positive and negative ion modes using multiple reaction monitoring (MRM). Each calibration curve had a high R2 value of >0.99. The method accuracies ranged -7.09-11.05 % and precision values were less than 14.36 %. The recovery, matrix effect, selectivity, stability, and carry-over of the method were in accordance with the relevant requirements. It was successfully applied for the investigation of the pharmacokinetics of these five constituents after oral administration of areca nut extract. Pharmacokinetic results indirectly indicated a metabolic relationship between the four areca nut alkaloids in rats. For further clarification of its pharmacodynamic basis, this study provided a theoretical reference.

In vitro bloodbrain barrier permeability study of four main active ingredients from Alpiniae oxyphyllae fructus.

The fruits of Alpinia oxyphylla Miq., a broadly utilized traditional Chinese medicine, have a number of effects on the central nervous system (CNS). The main active constituents of Alpiniae oxyphyllae fructus (AOF) were nootkatone, tectochrysin, chrysin and protocatechuic acid. An immortalized human brain microvascular endothelial cell (hCMEC/D3) and astrocyte (HA1800) coculture model was used to investigate the permeability of the blood-brain barrier (BBB). The validation of ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) methods for the four compounds was conducted following industry guidelines. Calibration curves were generated with mean coefficients (R2) better than 0.99. The inter-day and intra-day precisions were less than 8.53% and 7.12%, respectively. The accuracies were lower than ± 11.57%, and recoveries were greater than 86.07%. The samples of the transport experiment were examined, and the apparent permeability coefficients (Papp) were calculated. The efflux ratios of the four compounds are all less than 2. The Papp values of protocatechuic acid, chrysin, nootkatone, tectochrysin were at the level of 10-5, 10-6, 10-6, and 10-7 cm/s, respectively. All four compounds crossed the BBB by passive diffusion, with protocatechuic acid having high permeability, and tectochrysin having poor permeability. This research indicated the permeability of protocatechuic acid, chrysin, nootkatone and tectochrysin through the BBB and offered a foundation for related research on AOF in the treatment of CNS illnesses.

A ratiometric fluorescence sensor for tetracycline detection based on two fluorophores derived from Partridge tea.

Blue fluorescent carbon dots (PCDs) were prepared by hydrothermal method with Partridge tea. The ethanol extract of Partridge tea (PEE) was found to emit red fluorescence. Thus, a novel ratiometric sensor was constructed by simply mixing the two fluorophores derived from Partridge tea. The presence of tetracycline (TET) at lower concentrations enhanced the emission peak at 508 nm of PCDs and had a negligible effect on the emission peak at 680 nm of PEE. TET at higher concentrations led to  quenching  both the fluorescence of PCDs and PEE via inner filter effect and fluorescence resonance energy transfer, separately. Good linearities for the detection of TET were obtained in the ranges 0.67 to 15.00 µM and 33.33 to 266.67 µM, with limit of detection of 0.095 µM. The sensor was successfully applied to detect TET in lake water and milk samples with good recoveries ranging from 93.27 ± 4.04% to 107.30 ± 6.16%. This study provided a simple, selective, sensitive, rapid, and environmentally friendly method of monitoring TET residues in the environment and food.

Preparation of thioglycerol-modified silica through thiol-epoxy click reaction and its application in HILIC for detection of oligosaccharide in beverages.

A novel preparation scheme of thioglycerol-modified silica through thiol-epoxy click reaction was proposed aiming at introducing additional quantities of hydroxyl groups into the structure. When applied as the stationary phase of hydrophilic interaction liquid chromatography (HILIC) for separation of oligosaccharide compounds, the material revealed higher polar separation capability than which synthesized through traditional thiol-ene click reaction. Hydrogen-bond interactions were speculated to be the predominant retention mechanism, while partitioning also participated in the retention of disaccharides and trisaccharides. The column also showed good stability and inter-batch reproducibility. Finally, the column was employed for determination of oligosaccharide compounds in commercial beverages, and good linearities, high accuracy, favorable precision, satisfactory reproducibility and resistance to matrix interference were achieved. In the detection of real samples, the determined content was consistent with the labeled content. This work provided an efficient and practicable method for quantity monitoring of commercial diet drinks in routine laboratory.

Novel ß-cyclodextrin doped carbon dots for host-guest recognition-assisted sensing of isoniazid and cell imaging.

In the present study, novel ß-cyclodextrin doped carbon dots (CCDs) were prepared via a simple one-pot hydrothermal method at a mild temperature (140 °C), using mixtures of ß-cyclodextrin and citric acid as precursors. By characterizing the chemical properties of CCDs prepared at 140 °C and 180 °C, the importance of low-temperature reaction for preservation of the specific structure of ß-CD was elucidated. The CCDs showed excellent optical properties and were stable to changes in pH, ionic strength and light irradiation. Since the fluorescence of the CCDs could be selectively quenched by isoniazid (INZ) through specific host-guest recognition effects, a convenient isoniazid fluorescence sensor was developed. Under the optimal conditions, the sensor exhibited a relatively low detection limit of 0.140 µg mL-1 and a wide detection range from 0.2 µg mL-1 to 50 µg mL-1 for INZ detection. Furthermore, the sensor was employed successfully for the determination of INZ in urine samples with satisfactory recovery (91.1-109.5%), displaying potential in clinical applications. Finally, low cytotoxicity of the prepared CCDs was confirmed using the CCK-8 method, followed by application in HepG2 cell imaging.

Amino Acid Profiling Study of Psidium guajava L. Leaves as an Effective Treatment for Type 2 Diabetic Rats.

Type 2 diabetes mellitus (T2DM) has become a major disease threatening human health worldwide. At present, the treatment of T2DM cannot cure diabetes and is prone to many side effects. Psidium guajava L. leaves have been reported to possess hypoglycemic activity, and they have been widely used in diabetes treatment in the folk. However, the antidiabetic mechanism has not been clearly explained. Also, the change in amino acid profile can reflect a metabolic disorder and provide insights into system-wide changes in response to physiological challenges or disease processes. The study found that P. guajava L. leaves can decrease fasting blood glucose and lipid levels in type 2 diabetic rats induced by streptozotocin. Through the analysis of amino acid profiling following 20 days of gavage administration, the concentration data were modeled by principal component analysis and orthogonal partial least squares discriminant analysis to find the different metabolites and related metabolic pathways (including cysteine and methionine metabolism, valine, leucine, and isoleucine biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis) for the explanation of the hypoglycemic mechanism of P. guajava L., which provides an experimental and theoretical basis for diabetes prediction and for the development of new drugs for the treatment of diabetes.

Photodegradation kinetics, transformation, and toxicity prediction of ketoprofen, carprofen, and diclofenac acid in aqueous solutions.

Photodegradation of 3 commonly used nonsteroidal anti-inflammatory drugs, ketoprofen, carprofen, and diclofenac acid, was conducted under ultraviolet (UV) irradiation. The kinetic results showed that the 3 pharmaceuticals obeyed the first-order reaction with decreasing rate constants of 1.54 × 10-4 , 5.91 × 10-5 , and 7.78 × 10-6 s-1 for carprofen, ketoprofen, and diclofenac acid, respectively. Moreover, the main transformation products were identified by ion-pair liquid-liquid extraction combined with injection port derivatization-gas chromatography-mass spectrometry and high-performance liquid chromatography-quadrupole-time of flight mass spectrometric analysis. There were 8, 3, and 6 transformation products identified for ketoprofen, carprofen, and diclofenac acid, respectively. Decarboxylation, dechlorination, oxidation, demethylation, esterification, and cyclization were proposed to be associated with the transformation of the 3 pharmaceuticals. Toxicity prediction of the transformation products was conducted on the EPI Suite software based on ECOSAR model, and the results indicate that some of the transformation products were more toxic than the parent compounds. The present study provides the foundation to understand the transformation behavior of the studied pharmaceuticals under UV irradiation. Environ Toxicol Chem 2017;36:3232-3239. © 2017 SETAC.