PREDICTIVE TOXICITY

Drug toxicity is one of the major reasons for drug attrition. Existing traditional methods do not have adequate in vitro predictability. Porsolt combines the most predictive cell models (e.g. primary cultures of target organs) with optimized assays specific to each type of toxicity, analysis and specific methods. We have accurate toxicity prediction in vitro services conducted in true target cells and within the physiological environment found with primary cultures.

PREDICTIVE TOXICITY CAPABILITIES

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PREDICTIVE TOXICITY

Cardiotoxicity

Cardiotoxicity describes the property of a substance that damages the heart muscle and/or tissue.

IN VITRO MODELS

Comprehensive in vitro Proarrhythmia Assay (CiPA):

Electrophysiology measurement (conventional manual patch-clamp)	Cardiac ion channels
Proarrhythmic risk assessment (MEA & Calcium transient assay)	human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs)

Drug Induced Vascular Injury

Drug Induced Vascular Injury (DIVI)

Drug-induced vascular injury (DIVI) in pre-clinical toxicology studies involves damage to endothelial and smooth muscle cells.

IN VITRO MODELS

Cell toxicity	HUVEC
Coagulation impairment Tissue Factor and Thrombomodulin	HUVEC
Leucocyte recruitment VCAM-1, E-Selectin and ICAM-1	HUVEC

Gastrointestinal System

Gastrointestinal system side effects are among the most common classes of adverse reactions associated with orally absorbed drugs.

IN VITRO MODELS

Gastric mucosal cell damage

Primary Rat gastric mucosal cells

General Toxicity

General Toxicity includes acute and preliminary chronic toxicity tests to help define and characterize the intrinsic toxicity of new substances.

IN VIVO MODELS

Acute toxicity	Rat – Mouse – Dog – Mini-pig
Preliminary chronic toxicity	Rat – Mouse

Hepatotoxicity

Hepatotoxicity is the injury or damage to the liver caused by exposure to a substance.

IN VITRO MODELS

Cholestasis & bile canaliculi network	Primary hepatocytes (R) sandwich configuration
Cytolysis (2D & 3D)	Primary hepatocytes (H,R & M) and HepG2
Oxidative stress: Glutathione (GSH) depletion	Primary hepatocytes (H & R) and HepG2
Phospholipidosis	Primary hepatocytes (H & R) and HepG2
Steatosis: intracellular lipid accumulation triglycerides	Primary hepatocytes (H & R) and HepG2

Nephrotoxicity

Nephrotoxicity is the deterioration or damage to the kidney function due to toxic effect of a substance.

IN VITRO MODELS

Cytolysis	Primary human renal proximal tubule epithelial cells Human renal proximal tubule epithelial cell line (HK-2) MDCK-II, CRFK,…
Lysosomal activity	Primary human renal proximal tubule epithelial cells Human renal proximal tubule epithelial cell line (HK-2)
Mitochondrial membrane potential	Primary human renal proximal tubule epithelial cells Human renal proximal tubule epithelial cell line (HK-2)

Neurotoxicity

Neurotoxicity is the effect caused to the normal activity of the nervous system by a substance.

IN VITRO MODELS

Cytolysis	Primary neurons (R,M) cell lines
Excitotoxicity Calcium measurement	Primary neurons (R,M) cell lines
Mitochondrial membrane potential	Primary neurons (R,M) cell lines
Neurite outgrowth	Primary neurons (R,M) cell lines

Skin Toxicity

Skin toxicity is the is the damage or deterioration of skin tissue after exposure to a substance.

IN VITRO MODELS

Cytotoxicity - Cell viability	3T3 & L929 fibroblasts
Ocular irritation (HET-CAM)	Chicken egg
Skin irritation	Reconstituted human epidermis
Skin sensitization	Monocyte cell line (THP1)

PREDICTIVE TOXICITY PUBLICATIONS

Porsolt

Z.A. de Glatigné
53940 Le Genest-Saint-Isle, France
Telephone +33 2 43 69 36 07

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