CODE 95311 ACADEMIC YEAR 2023/2024 CREDITS 5 cfu anno 1 MEDICAL-PHARMACEUTICAL BIOTECHNOLOGY 10598 (LM-9) - GENOVA SCIENTIFIC DISCIPLINARY SECTOR BIO/14 LANGUAGE English TEACHING LOCATION GENOVA SEMESTER 1° Semester MODULES Questo insegnamento è un modulo di: PHARMACOLOGY AND TOXICOLOGY AND LABORATORY TEACHING MATERIALS AULAWEB OVERVIEW The module of Toxicology is part of the integrated course of Pharmacology and Toxicology, which is taught during the first year of the Master's Degree in Biotechnology, and concerrns the study of the adverse effects of chemicals on living organisms. The module includes laboratory exercises. Lectures will be held in English. AIMS AND CONTENT 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, the 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; Toxicodynamics ) will be illustrated. Neurotoxicity will be discussed as an example of organ toxicity, with a particular focus on glutamatergic excitotoxicity and its role in neurodegenerative pathologies. Finally, toxicity tests for risk assessment will be illustrated. In laboratory exercises, students will learn in vitro and in vivo methods related to the study of the effects of xenobiotics in the CNS. TEACHING METHODS Lessons engaging students with scientific questions and reasonings. Use of the Wooclap platform for interactive student engagement. 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 AulaWeb portal. Lessons will be given face-to-face. In case of emergency (e.g., hydrogeologic emergency), lessons will be given online, using the Microsoft Teams platform. Students will be promptly informed by the teacher. SYLLABUS/CONTENT Introduction to Toxicology. Definition of xenobiotic, toxic agent and toxin. 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. Organ toxicity will be focused on 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. Toxicity tests. 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. Laboratory exercises. Preparation and purification of isolated nerve terminals (synaptosomes) Determination of synaptosome protein content by spectrophotometric analysis Assessment of synaptosome viability and response following exposure to xenobiotics by cytofluorimetric analysis Intracerebral microdialysis for in vivo pharmacological/toxicological studies in the central nervous system: theoretical and practical aspects. RECOMMENDED READING/BIBLIOGRAPHY Galli, Corsini, Marinovich. Tossicologia. Ed. Piccin; Greim, Deml. Tossicologia. Ed. Zanichelli; Curtis D. Klaassen. Casarett & Doull's. Toxicology. The basic science of poisons (9th edition). Ed.McGraw Hill Cantelli Forti, Galli, Hrelia, Marinovich. Tossicologia molecolare e cellulare. Ed. UTET. TEACHERS AND EXAM BOARD ERNESTO FEDELE Ricevimento: By appointment (tel. 010-3532659; e-mail: ernesto.fedele@unige.it). In presence or using the most common online platforms (Microsoft Teams, Zoom, Google Meet, Skype). MASSIMO GRILLI Ricevimento: on appointment Exam Board ERNESTO FEDELE (President) TULLIO FLORIO (President) ALESSANDRO CORSARO MASSIMO GRILLI LESSONS Class schedule The timetable for this course is available here: Portale EasyAcademy EXAMS EXAM DESCRIPTION The integrated course of Pharmacology and Toxicology involves an oral exam on the topics covered in the course. ASSESSMENT METHODS The assessment of learning outcomes will be carried out during the oral examination by evaluating the student's competence on the different topics of the course program, the use of appropriate scientific terminology and capabilities of scientific reasoning. Exam schedule Data appello Orario Luogo Degree type Note 15/02/2024 09:00 GENOVA Orale 05/06/2024 09:00 GENOVA Orale 02/07/2024 09:00 GENOVA Orale 02/07/2024 09:00 GENOVA Orale 30/07/2024 09:00 GENOVA Orale 30/10/2024 09:00 GENOVA Orale Agenda 2030 - Sustainable Development Goals Good health and well being