Yadav, Rakhee published the artcileRole of calcium ion channels and cytoskeletal proteins in Thorium-232 induced toxicity in normal human liver cells (WRL 68) and its validation in swiss mice, Application In Synthesis of 21829-25-4, the publication is Chemosphere (2022), 288(Part_2), 132557, database is CAplus and MEDLINE.
Hepatic disorders reported in humans exposed to Thorium-232 (Th-232) rationalizes the present study investigating the toxicol. response of normal human liver cells (WRL 68) and its validation in Swiss mice. Cell count anal. of WRL 68 cells-treated with Th-nitrate (1-200μM) estimated IC50 of ∼24μM (at 24 h) and 35μM (at 48 h). Anal. of cell viability (trypan blue assay) showed the IC50 of ∼172μM. Phase contrast bright-field microscopy revealed Th-induced morphol. changes and cell-released microvesicle-like structures in extracellular space. Th-estimation by ICP-MS (Inductively-coupled plasma mass-spectrometry) showed uptake of Th by cells as a function of concentration and incubation time. Employing DTPA as a chelating agent in cell harvesting solution, cell-internalized/strongly-bound Th was estimated to be ∼42% of total incubated Th. Th-uptake studies in the presence of ion-channel specific inhibitors (e.g. nifedipine, thapsigargin) revealed the role of plasma membrane calcium channels and cytoplasmic calcium in modulating the Th-uptake. Transmission electron microscopy of Th-treated cells showed cell-derived extracellular vesicles, alterations in the shape and size of nucleus and mitochondria as well as cytoplasmic inclusions. The order of Th accumulation in various sub-cellular protein fractions was found to be as cytoskeleton (43%) > cytoplasmic (15%) > chromatin (7%) > nuclear (5%) & membrane (5%). Immunofluorescence anal. of WRL 68 cells showed that Th significantly altered the expression of cytoskeleton proteins (F-actin and keratin), which was further validated in liver tissues of Swiss mice administered with Th-232. Findings herein highlight the role of calcium channels and cytoskeleton in Th-induced toxicity. Keywords: Thorium toxicity; Liver cells; Calcium channels; Sub-cellular targets, Cytoskeleton; Swiss Mice.
Chemosphere published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C8H6KNO4S, Application In Synthesis of 21829-25-4.
Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem