English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Carbamazepine and selegiline, although neuroprotective themselves, are presumed to have toxic metabolites. The aim of this study was to investigate the possible metabolism-induced toxicity of selegiline and carbamazepine with a novel in vitro method: The drugs were incubated with target cells (neuroblastoma SH-SY5Y) with or without a pre- incubation with mouse or human hepatocytes. The viability of SH-SY5Y cells was then measured by using total cellular ATP as an indicator of the cell viability. For the pre-incubation with hepatocytes two different methods were used: Hepa- tocytes were grown either in multiwell plates (Model 1) or in filter inserts (Model 2). Selegiline itself increased SH-SY5Y viability, but the pre-incubation with both mouse and human hepatocytes made se- legiline slightly toxic to SH-SY5Y cells. The biotransformation of carbamazepine seemed to be more complex and showed variation in different hepatocyte models. In general, human hepatocytes increased carbamazepine toxicity to SH- SY5Y cells, whereas mouse hepatocytes had no such effect. The methodology used (especially Model 1) could form a ba- sis in developing a test system for a qualitative detection of metabolism-induced (neuro)toxicity in the early phase of drug discovery. In this respect, the present study might be promising for further evaluation by means of a larger number of in- dependent experiments and different types of compounds.

Metabolism-Induced Toxicity of Selegiline and Carbamazepine Studied with an In Vitro Method