No abstract

Hydrogen sulfide exists widely in mammalian tissues and plays a vital role in physiological and pathophysiological processes. However, striking differences with orders of magnitude were observed for the detected hydrogen sulfide concentrations in biological matrices among different measurements in literature, which lead to the uncertainty for examination the biological relevance of hydrogen sulfide. Here, we developed and validated a liquid chromatography- mass spectrometry (LC-MS/MS) method for the determination of hydrogen sulfide in various biological matrices by determination of a derivative of hydrogen sulfide and monobromobimane named sulfide dibimane (SDB). 36S-labeled SDB was synthesized and validated for using as an internal standard. This method has been successfully used to measure hydrogen sulfide levels in a broad range of biological matrices, such as blood, plasma, tissues, cells, and enzymes, across different species. Moreover, a novel mode that hydrogen sulfide could loosely and non-covalently bind to human serum protein (HSA) and hemoglobin (HB) was revealed by using the developed method.

The absorption and transport mechanisms of berberine, palmatine, jateorhizine, and coptisine were studied using a Caco-2 cells uptake and transport model, with the addition of cyclosporin A and verapamil as P-glycoprotein (P-gp) inhibitors and MK-571 as a multidrug resistance-associated protein 2 (MRP(2)) inhibitor. In the uptake experiment, berberine, palmatine, jateorhizine, and coptisine were all taken into Caco-2 cells, and their uptakes were increased in the presence of cyclosporin A or verapamil. In the transport experiment, P(app) (AP-BL) was between 0.1 and 1.0 × 10(6) cm/sec for berberine, palmatine, jateorhizine, and coptisine and was lower than P(app) (BL-AB). ER values were all >2. Cyclosporin A and verapamil both increased P(app) (AP-BL) but decreased P(app) (BL-AB) for berberine, palmatine, jateorhizine, and coptisine; ER values were decreased by >50%. MK-571 had no influence on the transmembrane transport of berberine, palmatine, jateorhizine, and coptisine. At a concentration of 1-100 μM, berberine, palmatine, jateorhizine, and coptisine had no significant effects on the bidirection transport of Rho123. Berberine, palmatine, jateorhizine, and coptisine were all P-gp substrates; and at the range of 1-100 μM, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.

This paper describes a metabonomic study characterizing the nephrotoxicity induced by aristolochic acid (AA), a suspected kidney toxicant. For these studies, we examined the biochemical compositions of AA-treated rat urine using LC-MS and pattern recognition methods. The biochemical and histological patterns of rat groups treated with different AA sources showed distinct differences from those of the control group. Certain metabolic pathways, such as homocysteine formation and the folate cycle were significantly accelerated, while others, including arachidonic acid biosynthesis, were decreased. A subset-validation procedure using linear discriminant analysis (LDA) and selected predictive variables indicated that approximately 95% of the treated and nontreated rat urine samples were classified correctly into their respective treatment groups. The results suggested that this metabonomic approach is a promising methodology for the rapid in vivo screening of nephrotoxicity associated with ingesting multi-ingredient medicinal herb supplements, and provides a valid method for comprehending the chemical-induced perturbations in the metabolic network and the networked lesions.

An efficient, mild and practical method for the reduction of aromatic nitro compounds using Ni/SiO 2 as catalyst is reported. The catalyst has been prepared and characterized by XRD, FT-IR, TEM, SEM successfully. The Ni loading is about 55 wt.%. The prominent merit of the Ni/SiO 2 catalyst passivated with a gas mixture is that it can be stored safely in air below 423 K and needs no activation before use. In the catalytic test, Ni/SiO 2 is found to be a highly efficient and reusable catalyst for the reduction of various aromatic nitro compounds. This catalyst is applicable for the preparation of various aromatic amines with different groups, the conversion and selectivity are almost up to 100%. Moreover, it is inexpensive, can be prepared and scaled up easily.

An inorganic–organic hybrid fluorescence chemosensor (DA/SBA-15) was prepared by covalent immobilization of a dansylamide derivative into the channels of mesoporous silica material SBA-15 via (3-aminopropyl)triethoxysilane (APTES) groups. The primary hexagonally ordered mesoporous structure of SBA-15 was preserved after the grafting procedure. Fluorescence characterization shows that the obtained inorganic–organic hybrid composite is highly selective and sensitive to Hg2+ detection, suggesting the possibility for real-time qualitative or quantitative detection of Hg2+ and the convenience for potential application in toxicology and environmental science.

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the mean C max of midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0–12, C max, and t 1/2 of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.

Myricetin, a naturally occurring flavonol, shows multifarious pharmacological activities, e.g., antidiabetic, antioxidant, anti-inflammatory, antitumor, and liver protection effects. In order to obtain an understanding of the myricetin's metabolism in vivo, a rapid and sensitive method by high-performance liquid chromatography coupled with electrospray-ionization mass spectrometry (HPLC-MS n ) techniques was employed to investigate the biotransformation in rats after oral administration of myricetin. Recognition and structural exposition of the metabolites were operated by comparing the changes in molecular mass (DM) and MS n spectra with the parent drug. As a result, the parent compound and seven metabolites were found in rat plasma, urine, and feces. In addition, besides 3,5-dihydroxyphenylacetic acid (M1) and 3,4,5-trihydroxyphenylacetic acid (M2), five other compounds were first discovered in the metabolite research of myricetin. These results indicated that, besides ring-fission, there were methylate (M3, M4, M5) and glucuronide (M6, M7) biotransformations of myricetin occurring in vivo.