Molecular Toxicology

Full course description

Human molecular toxicology studies the molecular mechanisms underlying toxicity of compounds in man. The conversion to reactive intermediates and metabolites is key in the actual toxicity of compounds. Therefore, the role of metabolism in the formation of metabolites and reactive intermediates and the protection against these species is extensively addressed. Moreover, compounds generally display a toxicity that is restricted to a specific organ and type of toxicity. This concept of selective toxicity is elaborated. Focus is on redox-controlled processes in biotransformation and in modulation of cell function. Topics include a survey of the molecular mechanisms determining (selective) toxicity; the versatility of enzymes, such as cytochrome P450 and glutathione S-transferases in the biotransformation of compounds; consequences of genetic polymorphisms of biotransformation enzymes; chemical and biological properties of various classes of reactive intermediates; structure-activity relationships and other approaches applied to predict metabolism; and strategies to reduce toxicity including those employed in Chinese traditional medicine.

Course objectives

To gain knowledge on experimental approaches to identify and quantify metabolites, reactive intermediates and their selective interaction with specific cellular target molecules (selective toxicity);
To get acquainted with the procedures applied to assess the toxicity of drugs and chemicals;
To understand the role of bio activation and bio-inactivation in the toxicity of drugs and other xenobiotics and natural toxins;
To be able to apply strategies used to predict toxicity;
To understand strategies to reduce or prevent toxicity;
To understand risk factors involved in inter-individual susceptibility to xenobiotics, including genetic polymorphisms, drug-drug and food-drug interactions.

Prerequisites

None

Co-requisites

None

Molecular Toxicology