LEARNING OUTCOMES

The Toxicology module aims at providing students with the basic knowledge regarding the interactions between xenobiotics and living organisms and the mechanisms through which such interactions can lead to harmful effects.

AIMS AND LEARNING OUTCOMES

Students will acquire the fundamentals of Toxicology, the basic notions of toxicokinetics and toxicodynamics, and learn the basic concepts related to the evaluation of toxicity.

To this purpose, tha course will address the mechanisms with which xenobiotics penetrate the body, are distributed, metabolized and eliminated and the factors that influence these processes and the toxic effect (Toxicokinetics). Furthermore, the main mechanisms of cell toxicity (radical production, alterations in calcium homeostasis, mitochondrial damage, genotoxicity, chemical carcinogenesis and developmental toxicity) and the action of different natural toxins (Toxicodynamics) will be illustrated. With regard to organ toxicity, neurotoxicity will be treated with a particular focus on glutamatergic excitotoxicity and its role in neurodegenerative pathologies. Finally, toxicity tests and methods for toxicological risk assessment for humans will be illustrated.

In laboratory exercises, students will learn in vitro and in vivo methods for studying the release of neurotransmitters and the effects of xenobiotics.

TEACHING METHODS

Lessons with active learning techniques engaging students with scientific questions and reasonings. All the course topics will be illustrated in great detail during the lectures. The teaching materials used during the lectures will be available for students on the website of AulaWeb.

Given the extension of Covid-19 emergency and to minimize risks for students, lessons will be delivered by videoconference using the  Microsoft Teams online platform. Students will be promptly informed of any change by AulaWeb.

SYLLABUS/CONTENT

Introduction to Toxicology. Definition of toxic agent. General and specialist areas of toxicology. Local or systemic toxicity, immediate and delayed toxicity, reversible or irreversible toxicity.

Toxicokinetics. Factors influencing toxicity: absorbed dose, route of exposure, duration and frequency of exposure, toxication and detoxication processes, elimination rate.

Toxicodynamics. Reaction with the biological target: target attributes, types of reaction with the target, effects on the target. Major cellular toxicity mechanisms: structural damage or dysfunction. Oxidative stress, mitochondrial toxicity, alteration of calcium homeostasis. Methods for the measurement of free radicals, of oxidative stress of phospholipids, proteins and DNA, of intracellular calcium. Cell death: necrosis, apoptosis,autophagy and regulated necrosis (necroptosis, parthanatos, ferroptosis, pyroptosis). Cellular and tissue repair mechanisms. Genotoxicity, chemical carcinogenesis and developmental toxicity. 

Drug interactions. Introduction. Pharmacokinetic and pharmacodynamic mechanisms of drug-drug, drug-herb and drug-food interactions. Consultation databases.

Organ toxicity. Due to time constraints, organ toxicity will be limited to neurotoxicity. Neurotoxicity: neuronopathies, axonopathies, myelinopathies, neurotransmission toxicity. Glutamate excitotoxicity: toxic effects of monosodium glutamate and of natural occuring agonists of glutamate receptors. Glutamate excitotoxicity and its role in acute and chronic disorders of the central nervous system (cerebral ischemia, Parkinson's disease, Huntington's Chorea, Alzheimer's disease, amyotrophic lateral sclerosis, multiple sclerosis, neuroAIDS). Adult neurogenesis: a mechanism of cell replacement and neurorepair.

Natural toxins. Molecular targets, mechanisms of action and their use in pharmaco-toxicological studies.

Toxicity tests and risk assessment. Acute toxicity test and determination of the LD50. Therapeutic index (TI) and margin of safety (MOS). Subacute, subchronic and chronic toxicity tests. Short and long-term carcinogenesis tests. Genotoxicity tests. Developmental toxicity test. Risk assessment methods.

Laboratory exercises. Superfused synaptosomes and gliosomes for the study of neurotoxin effects.  Intracerebral microdialysis to study the effects of xenobiotics in vivo.

RECOMMENDED READING/BIBLIOGRAPHY

Galli, Corsini, Marinovich. Tossicologia. Ed. Piccin;

Greim, Deml. Tossicologia. Ed. Zanichelli;

Klaasen , Watkins III.  Casarett & Doull's. Elementi di Tossicologia. Ed. Ambrosiana;

Cantelli Forti, Galli, Hrelia, Marinovich. Tossicologia molecolare e cellulare. Ed. UTET.