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Laboratory of Toxicology  

Lab. GalliCl

 

Director
Prof. Corrado L. Galli, corrado.galli@unimi.it

 

 

Collaborators
Emanuela Corsini, Associate Professor emanuela.corsini@unimi.it
Marina Marinovich, Associate Professor marina.marinovich@unimi.it
Patrizia Restani, Associate Professor patrizia.restani@unimi.it
Barbara Viviani, Assistant Professor barbara.viviani@unimi.it
Ellaine Ferioli, Secretary toxlab@unimi.it
Valentina Galbiati, PhD student valentina.galbiati@unimi.it
Mariaserena Boraso mariaserena.boraso@unimi.it
Chiara Di Lorenzo chiara.dilorenzo@unimi.it
Francesca Uberti, Research fellow allergia@unimi.it
Francesca Colombo, Research fellow francesca.colombo15@studenti.unimi.it
Yuri Manzoni, Research fellow yuri.manzoni@studenti.unimi.it

 

General Research Interests

Created in 1979, the primary function of the Laboratory of Toxicology is to study toxicological problems concerning food additives, with a concern of 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 and food safety.

 

Current Research Areas

Immunotoxicology/Immunopharmacology (Responsible: Emanuela Corsini)

The research program encompasses three distinct areas of immunotoxicology. 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 and keratinocytes, and to classify allergens according to their potency.  The other area of research centers on the understanding at the molecular level the mechanism of action of immunotoxic/immunomodulatory compounds (i.e. perfluorinated compounds, pesticides, vegetal extracts, anti-inflammatory drugs) on innate and adaptive immunity. Finally, immunosenescece represents the other area of interest of her laboratory. Specifically, studies are being conducted to define the role of RACK-1 and protein kinase C in the decline or remodeling of the immune responses associated with aging, and to identify compounds able to reverse such changes (i.e. DHEA, natural extracts).

Techniques

  • Human and rodent 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

Selected Publication

Corsini E, Sokooti M, Galli CL, Moretto A, Colosio C. Pesticide induced immunotoxicity in humans: A comprehensive review of the existing evidence. Toxicology. 2013 May 10;307:123-35.

Corsini E, Galbiati V, Mitjans M, Galli CL, Marinovich M. NCTC 2544 and IL-18 production: a tool for the identification of contact allergens. Toxicol In Vitro. 2013 Apr;27(3):1127-34.

Corsini E, Sangiovanni E, Avogadro A, Galbiati V, Viviani B, Marinovich M, Galli CL, Dell'Agli M, Germolec DR. In vitro characterization of the immunotoxic potential of several perfluorinated compounds (PFCs). Toxicol Appl Pharmacol. 2012 Jan 15;258(2):248-55.

Galbiati V, Carne A, Mitjans M, Galli CL, Marinovich M, Corsini E. Isoeugenol destabilizes IL-8 mRNA expression in THP-1 cells through induction of the negative regulator of mRNA stability tristetraprolin. Arch Toxicol. 2012 Feb;86(2):239-48.

Buoso E, Lanni C, Molteni E, Rousset F, Corsini E, Racchi M. Opposing effects of cortisol and dehydroepiandrosterone on the expression of the receptor for Activated C Kinase 1: implications in immunosenescence. Exp Gerontol. 2011 Nov;46(11):877-83.

 

Risk Assessment (Responsible: Marina Marinovich)

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, the role of calcium, reactive oxygen species, inflammatory mediators, activation of gene transcription in the onset and maintenance of the damage.

Techniques

  • Risk assessment deriving from the use of pesticides
  • 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
  • Characterization of biochemical processes involved in skin response to irritants or allergens
  • Quantitative risk assessment, which emphasizes reliance on numerical expressions of risk, qualitative expressions of risk, and indication of the attendant uncertainties

Selected Publications from 2001

1 Aspartame, low-calorie sweeteners and disease: regulatory safety and epidemiological issues
Marinovich M, Galli C.L., Bosetti C., Gallus S., La Vecchia C. Food and Chemical Toxicology, 2013 in pubblicazione.

2 Comparison of wood smoke PM2.5 obtained from the combustion of FIR and beech pellets on inflammation and DNA damage in A549 and THP-1 human cell lines.
Corsini E, Budello S, Marabini L, Galbiati V, Piazzalunga A, Barbieri P, Cozzutto S, Marinovich M, Pitea D, Galli CL. - Arch Toxicol. 2013 May 14. [Epub ahead of print]. PMID: 23670201

3 NCTC 2544 and IL-18 production: a tool for the identification of contact allergens.
Corsini E, Galbiati V, Mitjans M, Galli CL, Marinovich M. Toxicol In Vitro. 2013 Apr;27(3):1127-34. PMID: 23063874, doi: 10.1016/j.tiv.2012.05.018.

4 Skin immunosenescence: decreased receptor for activated C kinase-1 expression correlates with defective tumour necrosis factor-alpha production in epidermal cells.
Corsini E, Racchi M, Lucchi L, Donetti E, Bedoni M, Viviani B, Galli CL, Marinovich M. Br J Dermatol. 2009 Jan;160(1):16-25. doi: 10.1111/j.1365-2133.2008.08885.x. PMID: 18945317

5 Is the acceptable daily intake as presently used an axiom or a dogma?
C. L. Galli, M. Marinovich, M. Lotti. Toxicol Lett. 2008 Aug 15; 180(2): 93-9. PMID: 18588960, doi: 10.1016/j.toxlet.2008.06.003      .   

 

Food Chemistry and Toxicology (Responsible: Patrizia Restani)

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.

Techniques

  • 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

Selected Publications

C. Di Lorenzo, M. Dell’Agli, E. Sangiovanni, A. Dos Santos, F. Uberti, E. Moro, E. Bosisio, P. Restani. Correlation between catechin content and NF-kB inhibition by infusions of green and black tea. Plant Foods Hum Nutr (2013) 68:149-54.

C. Di Lorenzo, E. Moro, A. Dos Santos, F. Uberti, P.Restani. Could 1,3 dimethylamylamine (DMAA) in food supplements have a natural origin?            Drug Test Anal. (2013) 5:116-123 - DOI: 10.1002/dta. 1391           

C. Stockley, PL. Teissedre, M. Boban, C. Di Lorenzo, P. Restani.  Bioavailability of wine-derived phenolic compounds in humans: a review. Food Funct. (2012) 3: 995-1007.

C. Ballabio, F. Uberti, C. Di Lorenzo, A. Brandolini, E. Penas, P. Restani. Biochemical and immunochemical characterization of different varieties of amaranth (Amaranthus L.  ssp.) as a safe ingredient for gluten-free products. J. Agric. Food Chem. (2011) 59: 12969-74

P. Restani, C. Ballabio, C. Di Lorenzo, S. Tripodi, A. Fiocchi. Molecular aspects of milk allergens and their role in clinical events. Anal. Bioanal. Chem. (2009) 395:47-56.

 

Neurotoxicology (Responsible: Barbara Viviani)

The laboratory of Neurotoxicology has focused 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 focussed 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 working in vitro on understanding the pivotal role of proinflammatory cytokines and their associated transducing machinery (receptors and associated proteins) in orchestrating the post-synaptic glutamatergic response.

Techniques

  • 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

Selected Publications

Giatti S., Boraso MS, Melcangi RC, Viviani B. (2012) Neuroactive steroids, their metabolites and neuroinflammation J. Mol. Endocrinol. 49, R125-34.

F. Gardoni, M. Boraso, E. Zianni, E. Corsini, C.L. Galli, F. Cattabeni, M. Marinovich, M. Di Luca and B. Viviani (2011) Distribution of interleukin-1 receptor complex at the synaptic membrane driven by interleukin-1beta and NMDA stimulation J. Neuroinflammation 8, 14

B. Viviani, S. Bartesaghi, M. Binaglia, E. Corsini, M. Boraso,  E. Grazi, C.L. Galli, M. Marinovich (2008). Dithiocarbamate Propineb induces acetylcholine release through cytoskeletal actin depolymerization in PC12 cells. Toxicology Letters 182, 63-68

Viviani B., Gardoni F., Bartesaghi S., Corsini E., Facchi, Galli CL, DiLuca M., Marinovich M. (2006) IL-1beta released by gp120 drives neural death through tyrosine phosphorylation and trafficking of NMDA receptors. J. Biol. Chem.;  281: 30212-30222

B. Viviani, S. Bartesaghi, E. Corsini, P. Villa, P. Ghezzi, A. Garau, C.L. Galli, M. Marinovich (2005) Erythropoietin protects primary hippocampal neurons increasing the expression of brain-derived neurotrophic factor. J. Neurochem 93: 412-421. 

 

Genotoxicology  (Responsible: Laura Marabini)

Research activity is essentially focalized on genotoxiciy evaluation in vitro on different cell lines by alkaline and neutral comet tests, micronucleus assays and γ- 1H2X foci formation. Besides our aim is identify the molecular pathway of genotoxic substances (PCBs  mixtures, UV radiations, alkenylbenzene compounds) and possible protection system  (vegetable  polyphenol extracts).

Techiques 

  • 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 metho

Selected Publications

Braga P.C., Dal Sasso M.,  Lattuada N., Marabini L., Calò R., Antonacci R., Bertelli A., Falchi M. and Verducci P.  (2013). Antioxidant activity of Melilotus officinalis extract investigated by means of the radical scavenging activity, the chemiluminescence of human neutrophil bursts and lipoperoxidation assay. Journal of Medicinal Plants Research 7(7): 358-365.

L. Marabini, R. Calò, S.  Fucile (2011). Genotoxic Effects Of Polychlorinated  Biphenyls (PCB 153, 138, 101, 118) in a Fish Cell Line (RTG-2). Toxicology in Vitro 25 : 1045-1052.

P.C. Braga, M. Dal Sasso., M. Culici., A. Spallino., L. Marabini, T. Bianchi, G. Nappi (2010). Effects of sulphurous water on human neutrophil elastase release. Therapeutic Advances in Respiratory Disease  4(6): 333-340.

F. Maffei, F. Carbone, G. Cantelli Forti, A. Buschini, P. Poli, C. Rossi, L. Marabini, S.  Radice, E. Chiesara, P. Hrelia (2009). Drinking water quality: an in vitro approach for the assessment of cytotoxic and genotoxic load in water sampled along distribution system. Environment International 35 (7):1053-1061 

S.Radice, E. Chiesara, S. Fucile , L. Marabini  (2008). Different effects of PCB101, PCB118, PCB138       and PCB153 alone or mixed in MCF-7 breast cancer cells. Food and Chemical Toxicology 46, 2561-2567   

 

Links

Italian Toxicology Society
http://www.pharmtox.org/sitox/

Federation of European Toxicologists and Societies of Toxicology
http://www.eurotox.com/

International Union of Toxicology
http://www.iutox.org/

International Assembly for the Recognition of Toxicologists (IART)
http://www.iutox.org/iart.asp

European Food Safety Authority
http://www.efsa.eu.int/

European Commission Health and Consumer Protection Authority
http://europa.eu.int/comm/health/

Italian Health Authority
http://www.ministerosalute.it/

Italian Education and Research Authority
http://www.miur.it/

Association for the research of Children Allergies and Asthma
http://www.allegriallergia.org/

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