IN VITRO TOXICITY TESTING

in vitro Toxicity Testing

Liver, heart, kidney and brain drug-induced toxicities currently account for more than 70% of drug attrition and drug withdrawal.

Porsolt  has developed a range of organ-specific cell-based assays to better predict the potential toxicity of drug candidates prior to in vivo studies.

Porsolt provides comprehensive in vitro toxicology and safety pharmacology services to assess drug safety profiles early in the discovery process.

We perform functional toxicity assays and can investigate the signaling pathways involved in detoxification and oxidative stress induced by drugs, using highly predictive cellular models, such as primary cell cultures.

Assessment of drug safety profiles with comprehensive in vitro services

> The kidney plays an important role in the elimination of many drugs and their metabolites. Drug-induced nephrotoxicity is a widespread complication. Several drugs have been implicated, among them antibiotics, and particularly aminoglycosides. Porsolt developed a range of nephrotoxicity assays in high-throughput format to provide an early assessment of nephrotoxic effects.

> Cardiotoxicity and Hepatotoxicity are the two main reasons for withdrawal of approved drugs from the market. We can profile the potential liver toxicity of a compound, using, high throughput, and High Content Analysis (HCA) assays using primary human hepatocytes, HepG2, and customized assays with other liver cells, to evaluate multiple endpoints including cytotoxicity, mitochondrial toxicity, oxidative stress, apoptosis, phospholipidosis, and more. In addition, our portfolio includes manual patch clamp and calcium transient assay on hiPSC-CMs.

> Neurotoxicity represents frequent and troublesome side effects, making the central and peripheral nervous systems important targets of toxicological studies. Porsolt neurotoxicity assays are based on primary cultures of nerve cells for greater predictivity. Neurotoxic effects are quantified using either automated high-content imaging or live-content imaging, for accurate and fast toxicity screens.

Eurotox 2018: Impact of assay medium on calcium transient assays performed on human-induced pluripotent stem cell-derived cardiomyocytes

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used as a preclinical tool for detecting cardiotoxicity. iCell® Cardiomyocytes² (iCell², from Cellular Dynamics International (CDI)) were used in this work as the potential cardiotoxicity model. CDI recommends the use of serum supplemented growth medium for calcium assays, however, serum can potentially bind molecules and affect their potency. The aim of this study was therefore to evaluate the effects of a different assay medium, a Tyrode solution, on the contractile activity of hiPSC-CMs after treatment with Cisapride, Quinidine and Nifedipine.

SPS 2018: Diversity of primary hepatocyte models allow for choosing the best tools for hepatotoxicity assessments.

Hepatotoxicity is considered a major cause of attrition of drug candidates. One of the major reasons is the lack of accurate and predictive models of hepatotoxicity in the early stages of drug development. An array of specific read-outs, using high content imaging and flow cytometry, were established for analyzing the effects of compounds on cell viability (cytolysis), mitochondrial membrane depolarization (MMP), lipid contents and Glutathione depletion. Hepatocyte primary cultures from three different species, mouse, rat, and Human were used, allowing for the comparison of the relevance of these models for specific purposes.