Created in 1979, the primary goal of the Laboratory of Toxicology is to study the mechanism of action of toxic substances at molecular level and its relevance for human risk assessment. For the last two decades several areas of toxicological relevance have been created: in vitro alternative methods, skin toxicity, immunotoxicology, neurotoxicity, food safety and genotoxicity.

Research topics

- Hazard Identification and characterization
The activity is focused on hazard characterization, the qualitative and/or quantitative evaluation of the nature of the adverse effects associate with biological, chemical and physical agents through the identification and characterization of biochemical mechanisms involved in cell response to toxic agents, exploring molecular pathways such as the role of calcium, reactive oxygen species, inflammatory mediators, activation of gene transcription in the onset and maintenance of the damage.
- Cutaneous toxicity
At present, the primary focus of her laboratory centers on the refinement of alternative in vitro tests to identify and discriminate contact allergens from irritants and respiratory sensitizers, based on the use of DC-like cells, keratinocytes and reconstituted human epidermis, and to classify allergens according to their potency.
- Food Chemistry and Toxicology
The main interest of the laboratory is associated with Food Safety, including the safety of dietetic products developed for specific groups of consumers, such as subjects suffering from food allergy and intolerance. Another important research area includes quality control of plant food supplements, development of analytical methods for the detection of active substances and xenobiotics in foods and plant food supplements.
- Neurotoxicology
The laboratory focuses its attention on the functional and structural characterization of proteins and pathways involved in the neuroinflammatory response and its relevance for neuronal function. The laboratory has a solid experience in describing the mechanisms underlying glial activation, neuronal death/survival and glia-neurons crosstalk following toxic insults or reproducing a condition of damage. Particular attention is focused on: ionic channels, intracellular calcium homeostasis, signal transduction (phosphorylation pathways, trancription factors), cytokines (Interleukin -1beta, Tumor necrosis factor-alfa), neurotrofic factors (Erythropoietin). Currently, the group is focusing on the pivotal role of proinflammatory cytokines and their associated transducing machinery (receptors and associated proteins) in orchestrating the post-synaptic glutamatergic response and the development of the excitatory synapse in both pathological and toxicological contexts. Particular attention is devoted to the impact of environmental contaminants (i.e. heavy metals) and micronutrients as corrective approach. Part of the identified molecular mechanisms are under investigation to design novel drugs.
- Genotoxicology
Our research activity is essentially focused on in vitro genotoxicity evaluation on different cell lines (by alkaline and neutral comet tests, micronucleus and γ- H2X foci formation assays) and on the molecular pathways of several genotoxic substances (PCBs mixtures, UV radiations, alkenylbenzene compounds). Moreover, we study the molecular mechanisms behind the genotoxic damage and the DNA repair pathways, such as NER, evaluating the potential protective effect of different botanicals.

Techniques

• Integration of information on mechanism of action in the evaluation of risk identification of the mechanism of action of toxic substances at cellular and molecular level, mainly of environmental contaminants (pesticides, metals, solvents, etc…) and its relevance in the risk assessment for human beings
• Human leukocyte purification
• Immune functional assays. i.e. proliferation, cytokine production
• Cytotoxicity, antibody production, etc.
• Cell function analysis, i.e. cell viability, DNA and RNA synthesis
• Protein synthesis and expression, mRNA expression, reactive oxygen species generation
• Flow cytometer analysis of leukocyte subpopulations
• Western blot analysis
• Immunoenzymatic assay, i.e. ELISA
• Real-time polymerase chain reaction
• DNA array
• Chromatography (HPTLC, HPLC, LC-MS, affinity, ion exchanges, gel permeation)
• Electrophoretic technique (PAGE, SDS-PAGE, Isoelettrofocusing)
• Immunochemical techniques (ELISA, immunoblotting)
• Food analysis by enzymatic kit
• Chemical methods
• Cell cultures
• Measurement of calcium and ion homeostasis
• Cell death and viability: apoptosis and necrosis
• Measurement of oxidative damage
• Western blot analysis
• Immunoenzymatic assay, i.e. ELISA
• Real-time polymerase chain reaction
• Confocal microscopy
• Evaluation of genotoxic damage (DNA fragmentation and repair) by micronucleus test, electrophoresis /fluorescence microscopy (comet test), immunohistochemical analysis
• Oxidative stress evaluation (LPO, ROS, CAT, SOD, GSH/CSSSG) spectro-fluorimetric methods
• Cytotoxicity assay, apoptosis / necrosis by biochemical enzymatic analysis and flow cytometry methods
• Evaluation of the expression of key genes involved in DNA damage signaling, repair and apoptosis induction

Selected publications

1: Berardesca E, Zuberbier T, Sanchez Viera M, Marinovich M. Review of the safety of octocrylene used as an ultraviolet filter in cosmetics. J Eur Acad Dermatol Venereol. 2019 Nov;33 Suppl 7:25-33.
doi: 10.1111/jdv.15945. Review. PubMed PMID: 31588614.

2: Galbiati V, Cornaghi L, Papale A, Donetti E, Marinovich M, Corsini E. Study on the inflammasome nlrp3 and blimp-1/nlrp12 after keratinocyte exposure to contact allergens. Toxicol Lett. 2019 Oct 1;313:130-136.
doi: 10.1016/j.toxlet.2019.07.003. Epub 2019 Jul 2. PubMed PMID: 31276767.

3: Marabini L, Galli CL, La Fauci P, Marinovich M. Effect of plant extracts on the genotoxicity of 1'-hydroxy alkenylbenzenes. Regul Toxicol Pharmacol. 2019 Jul;105:36-41.
doi: 10.1016/j.yrtph.2019.03.017. Epub 2019 Mar 29. PubMed PMID: 30935955.

4: Corsini E, Ozgen S, Papale A, Galbiati V, Lonati G, Fermo P, Corbella L, Valli G, Bernardoni V, Dell'Acqua M, Becagli S, Caruso D, Vecchi R, Galli CL, Marinovich M. Insights on wood combustion generated proinflammatory ultrafine particles (UFP). Toxicol Lett. 2017 Jan 15;266:74-84.
doi: 10.1016/j.toxlet.2016.12.005. Epub 2016 Dec 15. PubMed PMID: 27988394.

5: Bal-Price A, Hogberg HT, Crofton KM, Daneshian M, FitzGerald RE, Fritsche E, Heinonen T, Hougaard Bennekou S, Klima S, Piersma AH, Sachana M, Shafer TJ, Terron A, Monnet-Tschudi F, Viviani B, Waldmann T, Westerink RHS, Wilks MF, Witters H, Zurich MG, Leist M. Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. ALTEX. 2018;35(3):306-352.
doi: 10.14573/altex.1712081. Epub 2018 Feb 23. Erratum in: ALTEX. 2019;36(3):506. PubMed PMID: 29485663; PubMed Central PMCID: PMC6545888.