Studying the intracellular bile acid concentration and toxicity in drug-induced cholestasis: Comprehensive LC-MS/MS analysis with human liver slices.

Drug-induced cholestasis (DIC) is a leading cause of drug-induced liver injury post-drug marketing, characterized by bile flow obstruction and toxic bile constituent accumulation within hepatocytes. This study investigates the toxicity associated with intracellular bile acid (BA) accumulation during DIC development. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, we examined intracellular BA concentrations in human precision-cut liver slices (PCLS) following the administration of cyclosporin A and chlorpromazine, both with and without an established BA mixture.

The Promiscuity of Squalene Synthase-Like Enzyme: Dehydrosqualene Synthase, a Natural Squalene Hyperproducer?

Dehydrosqualene synthase (CrtM), as a squalene synthase-like enzyme from , can naturally utilize farnesyl diphosphate to produce dehydrosqualene (CH). However, no study has documented the natural production of squalene (CH) by CrtM. Here, based on an HPLC-Q-Orbitrap-MS/MS study, we report that the expression of or in 168 both results in the output of squalene, dehydrosqualene, and phytoene (CH).

Online coupling of a catalytic continuous microflow reactor to mass spectrometry.

Flow cell reactors used for catalyst development and applications are upcoming due to their small environmental and economic footprint. Online microflow reactor coupling with mass spectrometry (MS) opens new possibilities for monitoring catalyst performance and identifying reaction products in real time. This is demonstrated for the metabolic relevant dealkylation of lidocaine on catalytic gold micro-particles using regular liquid chromatography modules.

Functionalized Fluorescent Nanodiamonds for Simultaneous Drug Delivery and Quantum Sensing in HeLa Cells.

Here, we present multifunctional fluorescent nanodiamonds (FNDs) for simultaneous drug delivery and free radical detection. For this purpose, we modified FNDs containing nitrogen vacancy (NV) centers with a diazoxide derivative. We found that our particles enter cells more easily and are able to deliver this cancer drug into HeLa cells.

Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits.

The biocide tetrakis(hydroxymethyl)phosphonium sulphate (THPS) and other members of the tetrakis(hydroxymethyl) phosphonium salts (THPX) family are associated with liver toxicity in several mammalian species and teratogenicity in rabbits. Malformations include skeletal changes and abnormalities in eye development and are very similar to those seen with vitamin A deficiency or excess. For this reason, it was hypothesized that teratogenicity of THPS(X) might be attributed to disturbances in retinol availability and/or metabolism as a result of maternal toxicity, for example, either due to insufficient dietary intake by the mothers or due to liver toxicity.