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Dr. Marco Pelin
Università degli Studi di Trieste, Department of Life Science, Trieste, Italy

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0 Inflammation
0 Pharmacology
0 Toxicology
0 Marine Toxins
0 skin toxicity

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Marine Toxins
Oral toxicity
Methods of detection
Inflammation
skin toxicity
Algal toxins

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Paper
Published: 21 October 2020 in Environmental Science: Nano
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The environmental impact of graphene oxide was evaluated on the model organism Artemia franciscana for ecotoxicological studies considering different biological parameters.

ACS Style

Federica Cavion; Laura Fusco; Silvio Sosa; Chiara Manfrin; Beatriz Alonso; Amaia Zurutuza; Roberto Della Loggia; Aurelia Tubaro; Maurizio Prato; Marco Pelin. Ecotoxicological impact of graphene oxide: toxic effects on the model organism Artemia franciscana. Environmental Science: Nano 2020, 7, 3605 -3615.

AMA Style

Federica Cavion, Laura Fusco, Silvio Sosa, Chiara Manfrin, Beatriz Alonso, Amaia Zurutuza, Roberto Della Loggia, Aurelia Tubaro, Maurizio Prato, Marco Pelin. Ecotoxicological impact of graphene oxide: toxic effects on the model organism Artemia franciscana. Environmental Science: Nano. 2020; 7 (11):3605-3615.

Chicago/Turabian Style

Federica Cavion; Laura Fusco; Silvio Sosa; Chiara Manfrin; Beatriz Alonso; Amaia Zurutuza; Roberto Della Loggia; Aurelia Tubaro; Maurizio Prato; Marco Pelin. 2020. "Ecotoxicological impact of graphene oxide: toxic effects on the model organism Artemia franciscana." Environmental Science: Nano 7, no. 11: 3605-3615.

Journal article
Published: 15 August 2020 in Nanomaterials
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In the frame of graphene-based material (GBM) hazard characterization, particular attention should be given to the cutaneous effects. Hence, this study investigates if HaCaT skin keratinocytes exposed to high concentrations of few-layer graphene (FLG) or partially dehydrated graphene oxide (d-GO) for a short time can recover from the cytotoxic insult, measured by means of cell viability, mitochondrial damage and oxidative stress, after GBM removal from the cell medium. When compared to 24 or 72 h continuous exposure, recovery experiments suggest that the cytotoxicity induced by 24 h exposure to GBM is only partially recovered after 48 h culture in GBM-free medium. This partial recovery, higher for FLG as compared to GO, is not mediated by autophagy and could be the consequence of GBM internalization into cells. The ability of GBMs to be internalized inside keratinocytes together with the partial reversibility of the cellular damage is important in assessing the risk associated with skin exposure to GBM-containing devices.

ACS Style

Marco Pelin; Hazel Lin; Arianna Gazzi; Silvio Sosa; Cristina Ponti; Amaya Ortega; Amaia Zurutuza; Ester Vázquez; Maurizio Prato; Aurelia Tubaro; Alberto Bianco. Partial Reversibility of the Cytotoxic Effect Induced by Graphene-Based Materials in Skin Keratinocytes. Nanomaterials 2020, 10, 1602 .

AMA Style

Marco Pelin, Hazel Lin, Arianna Gazzi, Silvio Sosa, Cristina Ponti, Amaya Ortega, Amaia Zurutuza, Ester Vázquez, Maurizio Prato, Aurelia Tubaro, Alberto Bianco. Partial Reversibility of the Cytotoxic Effect Induced by Graphene-Based Materials in Skin Keratinocytes. Nanomaterials. 2020; 10 (8):1602.

Chicago/Turabian Style

Marco Pelin; Hazel Lin; Arianna Gazzi; Silvio Sosa; Cristina Ponti; Amaya Ortega; Amaia Zurutuza; Ester Vázquez; Maurizio Prato; Aurelia Tubaro; Alberto Bianco. 2020. "Partial Reversibility of the Cytotoxic Effect Induced by Graphene-Based Materials in Skin Keratinocytes." Nanomaterials 10, no. 8: 1602.

Journal article
Published: 14 August 2020 in International Journal of Molecular Sciences
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The marine polyether palytoxin (PLTX) is one of the most toxic natural compounds, and is involved in human poisonings after oral, inhalation, skin and/or ocular exposure. Epidemiological and molecular evidence suggest different inter-individual sensitivities to its toxic effects, possibly related to genetic-dependent differences in the expression of Na+/K+-ATPase, its molecular target. To identify Na+/K+-ATPase subunits, isoforms correlated with in vitro PLTX cytotoxic potency, sensitivity parameters (EC50: PLTX concentration reducing cell viability by 50%; Emax: maximum effect induced by the highest toxin concentration; 10−7 M) were assessed in 60 healthy donors’ monocytes by the MTT (methylthiazolyl tetrazolium) assay. Sensitivity parameters, not correlated with donors’ demographic variables (gender, age and blood group), demonstrated a high inter-individual variability (median EC50 = 2.7 × 10−10 M, interquartile range: 0.4–13.2 × 10−10 M; median Emax = 92.0%, interquartile range: 87.5–94.4%). Spearman’s analysis showed significant positive correlations between the β2-encoding ATP1B2 gene expression and Emax values (rho = 0.30; p = 0.025) and between Emax and the ATP1B2/ATP1B3 expression ratio (rho = 0.38; p = 0.004), as well as a significant negative correlation between Emax and the ATP1B1/ATP1B2 expression ratio (rho = −0.30; p = 0.026). This toxicogenetic study represents the first approach to define genetic risk factors that may influence the onset of adverse effects in human PLTX poisonings, suggesting that individuals with high gene expression pattern of the Na+/K+-ATPase β2 subunit (alone or as β2/β1 and/or β2/β3 ratio) could be highly sensitive to PLTX toxic effects.

ACS Style

Marco Pelin; Gabriele Stocco; Chiara Florio; Silvio Sosa; Aurelia Tubaro. In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase β2 Subunit Isoform. International Journal of Molecular Sciences 2020, 21, 5833 .

AMA Style

Marco Pelin, Gabriele Stocco, Chiara Florio, Silvio Sosa, Aurelia Tubaro. In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase β2 Subunit Isoform. International Journal of Molecular Sciences. 2020; 21 (16):5833.

Chicago/Turabian Style

Marco Pelin; Gabriele Stocco; Chiara Florio; Silvio Sosa; Aurelia Tubaro. 2020. "In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase β2 Subunit Isoform." International Journal of Molecular Sciences 21, no. 16: 5833.

Journal article
Published: 28 January 2020 in Toxins
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Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg−1). At the dose of 220 µg kg−1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg−1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 μg kg−1 (95% confidence limits: 155–281 µg kg−1) and to estimate a provisional NOEL of 120 µg kg−1.

ACS Style

Silvio Sosa; Marco Pelin; Federica Cavion; Fabienne Hervé; Philipp Hess; Aurelia Tubaro. Acute Oral Toxicity of Pinnatoxin G in Mice. Toxins 2020, 12, 87 .

AMA Style

Silvio Sosa, Marco Pelin, Federica Cavion, Fabienne Hervé, Philipp Hess, Aurelia Tubaro. Acute Oral Toxicity of Pinnatoxin G in Mice. Toxins. 2020; 12 (2):87.

Chicago/Turabian Style

Silvio Sosa; Marco Pelin; Federica Cavion; Fabienne Hervé; Philipp Hess; Aurelia Tubaro. 2020. "Acute Oral Toxicity of Pinnatoxin G in Mice." Toxins 12, no. 2: 87.

Review
Published: 26 December 2019 in World Journal of Stem Cells
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Adverse drug reactions (ADRs) are major clinical problems, particularly in special populations such as pediatric patients. Indeed, ADRs may be caused by a plethora of different drugs leading, in some cases, to hospitalization, disability or even death. In addition, pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs, leading, in some cases, to more severe consequences. To improve the comprehension, and thus the prevention, of ADRs, the set-up of sensitive and personalized assays is urgently needed. Important progress is represented by the possibility of setting up groundbreaking patient-specific assays. This goal has been powerfully achieved using induced pluripotent stem cells (iPSCs). Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body, this model may be accurate in predicting drug toxicity, especially when this toxicity is related to individual genetic differences. This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs, with particular attention to drugs used in the pediatric field. We especially focused on the intestinal, hepatic, pancreatic, renal, cardiac, and neuronal levels, also discussing progress in organoids creation. The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine, liver, pancreas, kidney, heart, and brain. Based on the existing knowledge, these models are powerful and promising tools in multiple clinical applications including toxicity screening, disease modeling, personalized and regenerative medicine.

ACS Style

Elena Genova; Federica Cavion; Marianna Lucafò; Luigina De Leo; Marco Pelin; Gabriele Stocco; Giuliana Decorti. Induced pluripotent stem cells for therapy personalization in pediatric patients: Focus on drug-induced adverse events. World Journal of Stem Cells 2019, 11, 1020 -1044.

AMA Style

Elena Genova, Federica Cavion, Marianna Lucafò, Luigina De Leo, Marco Pelin, Gabriele Stocco, Giuliana Decorti. Induced pluripotent stem cells for therapy personalization in pediatric patients: Focus on drug-induced adverse events. World Journal of Stem Cells. 2019; 11 (12):1020-1044.

Chicago/Turabian Style

Elena Genova; Federica Cavion; Marianna Lucafò; Luigina De Leo; Marco Pelin; Gabriele Stocco; Giuliana Decorti. 2019. "Induced pluripotent stem cells for therapy personalization in pediatric patients: Focus on drug-induced adverse events." World Journal of Stem Cells 11, no. 12: 1020-1044.

Journal article
Published: 24 December 2019 in Carbon
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Skin provides the first interface between body and environment, representing one of the most feasible exposure routes to graphene-based materials (GBMs). However, interactions of GBMs with the skin are poorly understood. In particular, low-concentration effects have not been investigated. Here we explored the ability of endotoxin-free, few-layer graphene (FLG) and dehydrated graphene oxide (d-GO) to initiate an inflammatory response at the cutaneous level by using human HaCaT keratinocytes. HaCaT cell exposure to low concentrations (0.01–1.0 μg/mL) of FLG or d-GO did not affect cell viability. FLG triggered the secretion of pro-inflammatory tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, and IL-6, while d-GO, and to a lesser extent FLG, prompted IL-8 (CXCL8) production. However, conditioned medium from HaCaT cells exposed to FLG or d-GO had no effect on THP-1 monocyte activation. Moreover, co-culture experiments did not show any effect of FLG- or d-GO-treated HaCaT cells on THP-1 cell migration. These results suggest that while GBMs are able to initiate an inflammatory response in keratinocytes, this does not necessarily lead to activation of monocytes. The present findings are relevant for potential dermal exposures to GBMs in occupational settings as well as the use of GBMs for cutaneous applications such as in wearable sensors.

ACS Style

Laura Fusco; Marco Pelin; Sourav Mukherjee; Sandeep Keshavan; Silvio Sosa; Cristina Martín; Viviana González; Ester Vázquez; Maurizio Prato; Bengt Fadeel; Aurelia Tubaro. Keratinocytes are capable of selectively sensing low amounts of graphene-based materials: Implications for cutaneous applications. Carbon 2019, 159, 598 -610.

AMA Style

Laura Fusco, Marco Pelin, Sourav Mukherjee, Sandeep Keshavan, Silvio Sosa, Cristina Martín, Viviana González, Ester Vázquez, Maurizio Prato, Bengt Fadeel, Aurelia Tubaro. Keratinocytes are capable of selectively sensing low amounts of graphene-based materials: Implications for cutaneous applications. Carbon. 2019; 159 ():598-610.

Chicago/Turabian Style

Laura Fusco; Marco Pelin; Sourav Mukherjee; Sandeep Keshavan; Silvio Sosa; Cristina Martín; Viviana González; Ester Vázquez; Maurizio Prato; Bengt Fadeel; Aurelia Tubaro. 2019. "Keratinocytes are capable of selectively sensing low amounts of graphene-based materials: Implications for cutaneous applications." Carbon 159, no. : 598-610.

Article
Published: 03 December 2019 in The Pharmacogenomics Journal
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The aim of the study was to validate the impact of the single-nucleotide polymorphism rs2413739 (T > C) in the PACSIN2 gene on thiopurines pharmacological parameters and clinical response in an Italian cohort of pediatric patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). In ALL, PACSIN2 rs2413739 T allele was associated with a significant reduction of TPMT activity in erythrocytes (p = 0.0094, linear mixed-effect model, multivariate analysis considering TPMT genotype) and increased severe gastrointestinal toxicity during consolidation therapy (p = 0.049). A similar trend was present also for severe hematological toxicity during maintenance. In IBD, no significant effect of rs2413739 could be found on TPMT activity, however azathioprine effectiveness was reduced in patients carrying the T allele (linear mixed effect, p = 0.0058). In PBMC from healthy donors, a positive correlation between PACSIN2 and TPMT protein concentration could be detected (linear mixed effect, p = 0.045). These results support the role of PACSIN2 polymorphism on TPMT activity and mercaptopurine adverse effects in patients with ALL. Further evidence on PBMC and pediatric patients with IBD supports an association between PACSIN2 variants, TPMT activity, and thiopurines effects, even if more studies are needed since some of these effects may be tissue specific.

ACS Style

Raffaella Franca; Gabriele Stocco; Diego Favretto; Nagua Giurici; Irene del Rizzo; Franco Locatelli; Luciana Vinti; Andrea Biondi; Antonella Colombini; Franca Fagioli; Elena Barisone; Marco Pelin; Stefano Martellossi; Alessandro Ventura; Giuliana Decorti; Marco Rabusin. PACSIN2 rs2413739 influence on thiopurine pharmacokinetics: validation studies in pediatric patients. The Pharmacogenomics Journal 2019, 20, 415 -425.

AMA Style

Raffaella Franca, Gabriele Stocco, Diego Favretto, Nagua Giurici, Irene del Rizzo, Franco Locatelli, Luciana Vinti, Andrea Biondi, Antonella Colombini, Franca Fagioli, Elena Barisone, Marco Pelin, Stefano Martellossi, Alessandro Ventura, Giuliana Decorti, Marco Rabusin. PACSIN2 rs2413739 influence on thiopurine pharmacokinetics: validation studies in pediatric patients. The Pharmacogenomics Journal. 2019; 20 (3):415-425.

Chicago/Turabian Style

Raffaella Franca; Gabriele Stocco; Diego Favretto; Nagua Giurici; Irene del Rizzo; Franco Locatelli; Luciana Vinti; Andrea Biondi; Antonella Colombini; Franca Fagioli; Elena Barisone; Marco Pelin; Stefano Martellossi; Alessandro Ventura; Giuliana Decorti; Marco Rabusin. 2019. "PACSIN2 rs2413739 influence on thiopurine pharmacokinetics: validation studies in pediatric patients." The Pharmacogenomics Journal 20, no. 3: 415-425.

Journals
Published: 27 November 2019 in Nanoscale
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Graphene related materials, if prepared with non-irritant exfoliation agents, do not induce skin irritation on a 3D model of human epidermis, following the OECD guideline 439.

ACS Style

Laura Fusco; Marina Garrido; Cristina Martín; Silvio Sosa; Cristina Ponti; Alba Centeno; Beatriz Alonso; Amaia Zurutuza; Ester Vázquez; Aurelia Tubaro; Maurizio Prato; Marco Pelin. Skin irritation potential of graphene-based materials using a non-animal test. Nanoscale 2019, 12, 610 -622.

AMA Style

Laura Fusco, Marina Garrido, Cristina Martín, Silvio Sosa, Cristina Ponti, Alba Centeno, Beatriz Alonso, Amaia Zurutuza, Ester Vázquez, Aurelia Tubaro, Maurizio Prato, Marco Pelin. Skin irritation potential of graphene-based materials using a non-animal test. Nanoscale. 2019; 12 (2):610-622.

Chicago/Turabian Style

Laura Fusco; Marina Garrido; Cristina Martín; Silvio Sosa; Cristina Ponti; Alba Centeno; Beatriz Alonso; Amaia Zurutuza; Ester Vázquez; Aurelia Tubaro; Maurizio Prato; Marco Pelin. 2019. "Skin irritation potential of graphene-based materials using a non-animal test." Nanoscale 12, no. 2: 610-622.

Journal article
Published: 01 October 2019 in Stem Cell Research
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Crohn's disease is a debilitating and incurable chronic inflammatory bowel disease, affecting millions of individuals worldwide, with an increasing frequency. Surgery must be applicable in half of the cases often with a disabling course, and pharmacological treatments may have adverse complications. We generated three isogenic clones of iPSCs from peripheral blood mononuclear cells (PBMCs) of a patient with Crohn's Disease under pharmacological treatment without adverse effects. Sendai virus based vector was used and the iPSCs were characterized for genetic uniqueness, genomic integrity, pluripotency, and differentiation ability. These iPSCs will be a powerful tool to develop tailored therapies.

ACS Style

Gaetana Lanzi; Stefania Masneri; Rosalba Monica Ferraro; Elena Genova; Giovanna Piovani; Chiara Barisani; Marco Pelin; Gabriele Stocco; Giuliana Decorti; Matteo Bramuzzo; Silvia Giliani. Generation of 3 clones of induced pluripotent stem cells (iPSCs) from a patient affected by Crohn's disease. Stem Cell Research 2019, 40, 101548 .

AMA Style

Gaetana Lanzi, Stefania Masneri, Rosalba Monica Ferraro, Elena Genova, Giovanna Piovani, Chiara Barisani, Marco Pelin, Gabriele Stocco, Giuliana Decorti, Matteo Bramuzzo, Silvia Giliani. Generation of 3 clones of induced pluripotent stem cells (iPSCs) from a patient affected by Crohn's disease. Stem Cell Research. 2019; 40 ():101548.

Chicago/Turabian Style

Gaetana Lanzi; Stefania Masneri; Rosalba Monica Ferraro; Elena Genova; Giovanna Piovani; Chiara Barisani; Marco Pelin; Gabriele Stocco; Giuliana Decorti; Matteo Bramuzzo; Silvia Giliani. 2019. "Generation of 3 clones of induced pluripotent stem cells (iPSCs) from a patient affected by Crohn's disease." Stem Cell Research 40, no. : 101548.

Pharmacodynamics
Published: 28 August 2019 in European Journal of Clinical Pharmacology
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Idiopathic nephrotic syndrome (INS) is the most frequent form of childhood nephrotic syndrome. Steroids represent the best therapeutic option; however, inter-individual differences in their efficacy and side effects have been reported. To date, there is no way to predict patients' resistance and/or dependence. Alterations in the cytokine profile of INS patients might contribute to proteinuria and glomerular damage and affect drug sensitivity. The cytokine plasma levels were measured in 21 INS children at diagnosis to investigate the association among cytokines pattern and clinical response. Patients were selected on the basis of their clinical response: 7 steroid sensitive (SS), 7 dependent (SD), and 7 resistant (SR). Significant results were then analyzed in 41 additional pediatric INS patients. Within the 48 cytokines analyzed, macrophage migration inhibitory factor (MIF) was a good predictor of steroid response. Indeed, SR patients showed significantly higher MIF plasma levels compared with all others (p = 0.022; OR = 4.3, 95%CI = 1.2-25.4): a cutoff concentration of MIF > 501 pg/ml significantly discriminated SR patients (sensitivity = 85.7%, specificity = 71.4%). On the contrary, SD patients showed lower MIF plasma levels compared with others (p = 0.010; OR = 0.12, 95%CI = 9.2 × 10-3-6.7 × 10-1). Significant results were confirmed in the entire cohort. Our comprehensive cytokine analysis indicates that assessing MIF plasma levels at diagnosis could predict response to glucocorticoids in children with INS.

ACS Style

Eva Cuzzoni; Raffaella Franca; Sara De Iudicibus; Annalisa Marcuzzi; Marianna Lucafò; Marco Pelin; Diego Favretto; Elena Monti; William Morello; Luciana Ghio; Claudio La Scola; Francesca Mencarelli; Andrea Pasini; Giovanni Montini; Giuliana Decorti; Gabriele Stocco. MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome. European Journal of Clinical Pharmacology 2019, 75, 1675 -1683.

AMA Style

Eva Cuzzoni, Raffaella Franca, Sara De Iudicibus, Annalisa Marcuzzi, Marianna Lucafò, Marco Pelin, Diego Favretto, Elena Monti, William Morello, Luciana Ghio, Claudio La Scola, Francesca Mencarelli, Andrea Pasini, Giovanni Montini, Giuliana Decorti, Gabriele Stocco. MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome. European Journal of Clinical Pharmacology. 2019; 75 (12):1675-1683.

Chicago/Turabian Style

Eva Cuzzoni; Raffaella Franca; Sara De Iudicibus; Annalisa Marcuzzi; Marianna Lucafò; Marco Pelin; Diego Favretto; Elena Monti; William Morello; Luciana Ghio; Claudio La Scola; Francesca Mencarelli; Andrea Pasini; Giovanni Montini; Giuliana Decorti; Gabriele Stocco. 2019. "MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome." European Journal of Clinical Pharmacology 75, no. 12: 1675-1683.

Journal article
Published: 25 May 2019 in Toxins
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In September 2015, a massive occurrence of the Ostreopsis species was recorded in central Adriatic Kaštela Bay. In order to taxonomically identify the Ostreopsis species responsible for this event and determine their toxin profile, cells collected in seawater and from benthic macroalgae were analyzed. Conservative taxonomic methods (light microscopy and SEM) and molecular methods (PCR-based assay) allowed the identification of the species Ostreopsis cf. ovata associated with Coolia monotis. The abundance of O. cf. ovata reached 2.9 × 104 cells L−1 in seawater, while on macroalgae, it was estimated to be up to 2.67 × 106 cells g−1 of macroalgae fresh weight and 14.4 × 106 cells g−1 of macroalgae dry weight. An indirect sandwich immunoenzymatic assay (ELISA) and liquid chromatography–high-resolution mass spectrometry (LC-HRMS) were used to determine the toxin profile. The ELISA assay revealed the presence of 5.6 pg palytoxin (PLTX) equivalents per O. cf. ovata cell. LC-HRMS was used for further characterization of the toxin profile, which showed that there were 6.3 pg of the sum of ovatoxins (OVTXs) and isobaric PLTX per O. cf. ovata cell, with a prevalence of OVTXs (6.2 pg cell−1), while the isobaric PLTX concentration was very low (0.1 pg cell−1). Among OVTXs, the highest concentration was recorded for OVTX-a (3.6 pg cell−1), followed by OVTX-b (1.3 pg cell−1), OVTX-d (1.1 pg cell−1), and OVTX-c (0.2 pg cell−1).

ACS Style

Živana Ninčević Gladan; Jasna Arapov; Silvia Casabianca; Antonella Penna; Giorgio Honsell; Valentina Brovedani; Marco Pelin; Luciana Tartaglione; Silvio Sosa; Carmela Dell’Aversano; Aurelia Tubaro; Ante Žuljević; Branka Grbec; Matea Čavar; Mia Bužančić; Ana Bakrač; Sanda Skejić. Massive Occurrence of the Harmful Benthic Dinoflagellate Ostreopsis cf. ovata in the Eastern Adriatic Sea. Toxins 2019, 11, 300 .

AMA Style

Živana Ninčević Gladan, Jasna Arapov, Silvia Casabianca, Antonella Penna, Giorgio Honsell, Valentina Brovedani, Marco Pelin, Luciana Tartaglione, Silvio Sosa, Carmela Dell’Aversano, Aurelia Tubaro, Ante Žuljević, Branka Grbec, Matea Čavar, Mia Bužančić, Ana Bakrač, Sanda Skejić. Massive Occurrence of the Harmful Benthic Dinoflagellate Ostreopsis cf. ovata in the Eastern Adriatic Sea. Toxins. 2019; 11 (5):300.

Chicago/Turabian Style

Živana Ninčević Gladan; Jasna Arapov; Silvia Casabianca; Antonella Penna; Giorgio Honsell; Valentina Brovedani; Marco Pelin; Luciana Tartaglione; Silvio Sosa; Carmela Dell’Aversano; Aurelia Tubaro; Ante Žuljević; Branka Grbec; Matea Čavar; Mia Bužančić; Ana Bakrač; Sanda Skejić. 2019. "Massive Occurrence of the Harmful Benthic Dinoflagellate Ostreopsis cf. ovata in the Eastern Adriatic Sea." Toxins 11, no. 5: 300.

Journal article
Published: 08 May 2019 in Marine Drugs
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Azaspiracids (AZAs) are marine toxins that are produced by Azadinium and Amphidoma dinoflagellates that can contaminate edible shellfish inducing a foodborne poisoning in humans, which is characterized by gastrointestinal symptoms. Among these, AZA1, -2, and -3 are regulated in the European Union, being the most important in terms of occurrence and toxicity. In vivo studies in mice showed that, in addition to gastrointestinal effects, AZA1 induces liver alterations that are visible as a swollen organ, with the presence of hepatocellular fat droplets and vacuoles. Hence, an in vitro study was carried out to investigate the effects of AZA1, -2, and -3 on liver cells, using human non-tumor IHH hepatocytes. The exposure of IHH cells to AZA1, -2, or -3 (5 × 10-12-1 × 10-7 M) for 24 h did not affect the cell viability and proliferation (Sulforhodamine B assay and 3H-Thymidine incorporation assay), but they induced a significant concentration-dependent increase of mitochondrial dehydrogenases activity (MTT reduction assay). This effect depends on the activity of mitochondrial electron transport chain complex I and II, being counteracted by rotenone and tenoyl trifluoroacetone, respectively. Furthermore, AZAs-increased mitochondrial dehydrogenase activity was almost totally suppressed in the K+-, Cl--, and Na+-free media and sensitive to the specific inhibitors of KATP and hERG potassium channels, Na+/K+, ATPase, and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels. These results suggest that AZA mitochondrial effects in hepatocytes derive from an imbalance of intracellular levels of K+ and, in particular, Cl- ions, as demonstrated by the selective reduction of toxin effects by CFTR chloride channel inhibition.

ACS Style

Marco Pelin; Jane Kilcoyne; Chiara Florio; Philipp Hess; Aurelia Tubaro; Silvio Sosa. Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions. Marine Drugs 2019, 17, 276 .

AMA Style

Marco Pelin, Jane Kilcoyne, Chiara Florio, Philipp Hess, Aurelia Tubaro, Silvio Sosa. Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions. Marine Drugs. 2019; 17 (5):276.

Chicago/Turabian Style

Marco Pelin; Jane Kilcoyne; Chiara Florio; Philipp Hess; Aurelia Tubaro; Silvio Sosa. 2019. "Azaspiracids Increase Mitochondrial Dehydrogenases Activity in Hepatocytes: Involvement of Potassium and Chloride Ions." Marine Drugs 17, no. 5: 276.

Review
Published: 02 November 2018 in ACS Nano
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Graphene and its derivatives are heralded as ‘miracle’ materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.

ACS Style

Bengt Fadeel; Cyrill Bussy; Sonia Merino; Ester Vázquez; Emmanuel Flahaut; Florence Mouchet; Lauris Evariste; Laury Gauthier; Antti J. Koivisto; Ulla Vogel; Cristina Martín; Lucia G. Delogu; Tina Buerki-Thurnherr; Peter Wick; Didier Beloin-Saint-Pierre; Roland Hischier; Marco Pelin; Fabio Candotto Carniel; Mauro Tretiach; Fabrizia Cesca; Fabio Benfenati; Denis Scaini; Laura Ballerini; Kostas Kostarelos; Maurizio Prato; Alberto Bianco. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano 2018, 12, 10582 -10620.

AMA Style

Bengt Fadeel, Cyrill Bussy, Sonia Merino, Ester Vázquez, Emmanuel Flahaut, Florence Mouchet, Lauris Evariste, Laury Gauthier, Antti J. Koivisto, Ulla Vogel, Cristina Martín, Lucia G. Delogu, Tina Buerki-Thurnherr, Peter Wick, Didier Beloin-Saint-Pierre, Roland Hischier, Marco Pelin, Fabio Candotto Carniel, Mauro Tretiach, Fabrizia Cesca, Fabio Benfenati, Denis Scaini, Laura Ballerini, Kostas Kostarelos, Maurizio Prato, Alberto Bianco. Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment. ACS Nano. 2018; 12 (11):10582-10620.

Chicago/Turabian Style

Bengt Fadeel; Cyrill Bussy; Sonia Merino; Ester Vázquez; Emmanuel Flahaut; Florence Mouchet; Lauris Evariste; Laury Gauthier; Antti J. Koivisto; Ulla Vogel; Cristina Martín; Lucia G. Delogu; Tina Buerki-Thurnherr; Peter Wick; Didier Beloin-Saint-Pierre; Roland Hischier; Marco Pelin; Fabio Candotto Carniel; Mauro Tretiach; Fabrizia Cesca; Fabio Benfenati; Denis Scaini; Laura Ballerini; Kostas Kostarelos; Maurizio Prato; Alberto Bianco. 2018. "Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment." ACS Nano 12, no. 11: 10582-10620.

Journal article
Published: 22 August 2018 in Nanoscale
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The most significant routes associated with occupational exposure to graphene-based materials (GBMs) are the inhalation, cutaneous, ocular and oral ones. The manuscript presents a review of the in vivo toxicity data of GBMs after these exposure routes.

ACS Style

Marco Pelin; Silvio Sosa; Maurizio Prato; Aurelia Tubaro. Occupational exposure to graphene based nanomaterials: risk assessment. Nanoscale 2018, 10, 15894 -15903.

AMA Style

Marco Pelin, Silvio Sosa, Maurizio Prato, Aurelia Tubaro. Occupational exposure to graphene based nanomaterials: risk assessment. Nanoscale. 2018; 10 (34):15894-15903.

Chicago/Turabian Style

Marco Pelin; Silvio Sosa; Maurizio Prato; Aurelia Tubaro. 2018. "Occupational exposure to graphene based nanomaterials: risk assessment." Nanoscale 10, no. 34: 15894-15903.

Journal article
Published: 14 August 2018 in Toxins
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The marine algal toxin palytoxin (PLTX) and its analogues are some of the most toxic marine compounds. Their accumulation in edible marine organisms and entrance into the food chain represent their main concerns for human health. Indeed, several fatal human poisonings attributed to these compounds have been recorded in tropical and subtropical areas. Due to the increasing occurrence of PLTX in temperate areas such as the Mediterranean Sea, the European Food Safety Authority (EFSA) has suggested a maximum limit of 30 µg PLTX/kg in shellfish meat, and has recommended the development of rapid, specific, and sensitive methods for detection and quantitation of PLTX in seafood. Thus, a novel, sensitive cell-based ELISA was developed and characterized for PLTX quantitation in mussels. The estimated limits of detection (LOD) and quantitation (LOQ) were 1.2 × 10−11 M (32.2 pg/mL) and 2.8 × 10−11 M (75.0 pg/mL), respectively, with good accuracy (bias = 2.5%) and repeatability (15% and 9% interday and intraday relative standard deviation of repeatability (RSDr), respectively). Minimal interference of 80% aqueous methanol extract allows PLTX quantitation in mussels at concentrations lower than the maximum limit suggested by EFSA, with an LOQ of 9.1 µg PLTX equivalent/kg mussel meat. Given its high sensitivity and specificity, the cell-based ELISA should be considered a suitable method for PLTX quantitation.

ACS Style

Marco Pelin; Silvio Sosa; Valentina Brovedani; Laura Fusco; Mark Poli; Aurelia Tubaro. A Novel Sensitive Cell-Based Immunoenzymatic Assay for Palytoxin Quantitation in Mussels. Toxins 2018, 10, 329 .

AMA Style

Marco Pelin, Silvio Sosa, Valentina Brovedani, Laura Fusco, Mark Poli, Aurelia Tubaro. A Novel Sensitive Cell-Based Immunoenzymatic Assay for Palytoxin Quantitation in Mussels. Toxins. 2018; 10 (8):329.

Chicago/Turabian Style

Marco Pelin; Silvio Sosa; Valentina Brovedani; Laura Fusco; Mark Poli; Aurelia Tubaro. 2018. "A Novel Sensitive Cell-Based Immunoenzymatic Assay for Palytoxin Quantitation in Mussels." Toxins 10, no. 8: 329.

Review
Published: 04 July 2018 in Current Medicinal Chemistry
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Understanding the biological and molecular processes underlying human pathologies is fundamental in order to develop innovative approaches to treat or prevent them. Among the technologies that could provide innovative disease models, induced pluripotent stem cells (iPSCs) is one of the most promising. Indeed, one application of this technology is patient-specific disease modeling. iPSCs obtained by reprogramming patients’ cells collected from accessible tissues, have the unique capability to differentiate, under an adequate stimulus, into any human cell type. In particular, iPSCs technology can be applied to study drug adverse effects, that is a key part of the drug discovery process. Indeed, drug induced adverse effects are among the most common causes that lead to abandon the development of new candidate therapeutic molecules, increasing the cost of drug discovery. An innovative strategy that could be used in drug design to solve drug attrition rate, and to establish innovative pharmacological models, could be the application of iPSCs technology in the early stage of the drug discovery process to model druginduced adverse events. In this review, recently developed disease models based on iPSCs will be discussed, with a particular focus on available models of drugs’ adverse effect, in particular hepatic/pancreatic toxicity.

ACS Style

Elena Genova; Marco Pelin; Katsunori Sasaki; Fengming Yue; Gaetana Lanzi; Stefania Masneri; Alessandro Ventura; Gabriele Stocco; Giuliana Decorti. Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention. Current Medicinal Chemistry 2018, 25, 2826 -2839.

AMA Style

Elena Genova, Marco Pelin, Katsunori Sasaki, Fengming Yue, Gaetana Lanzi, Stefania Masneri, Alessandro Ventura, Gabriele Stocco, Giuliana Decorti. Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention. Current Medicinal Chemistry. 2018; 25 (24):2826-2839.

Chicago/Turabian Style

Elena Genova; Marco Pelin; Katsunori Sasaki; Fengming Yue; Gaetana Lanzi; Stefania Masneri; Alessandro Ventura; Gabriele Stocco; Giuliana Decorti. 2018. "Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention." Current Medicinal Chemistry 25, no. 24: 2826-2839.

Journals
Published: 11 June 2018 in Nanoscale
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Graphene based nanomaterials induce a reactive oxygen species-mediated mitochondrial depolarization, caused by the activation of NADH dehydrogenase and xanthine oxidase.

ACS Style

Marco Pelin; Laura Fusco; Cristina Martín; Silvio Sosa; Javier Frontiñán-Rubio; Jose Miguel González-Domínguez; Mario Durán-Prado; Ester Vázquez; Maurizio Prato; Aurelia Tubaro. Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase. Nanoscale 2018, 10, 11820 -11830.

AMA Style

Marco Pelin, Laura Fusco, Cristina Martín, Silvio Sosa, Javier Frontiñán-Rubio, Jose Miguel González-Domínguez, Mario Durán-Prado, Ester Vázquez, Maurizio Prato, Aurelia Tubaro. Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase. Nanoscale. 2018; 10 (25):11820-11830.

Chicago/Turabian Style

Marco Pelin; Laura Fusco; Cristina Martín; Silvio Sosa; Javier Frontiñán-Rubio; Jose Miguel González-Domínguez; Mario Durán-Prado; Ester Vázquez; Maurizio Prato; Aurelia Tubaro. 2018. "Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase." Nanoscale 10, no. 25: 11820-11830.

Journal article
Published: 01 April 2018 in Analytica Chimica Acta
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Surface-enhanced Raman spectroscopy (SERS) is a promising and emerging technique to analyze the cellular environment. We developed an alternative, rapid and label-free SERS-based method to get information about the cellular environment by analyzing cells lysates, thus avoiding the need to incorporate nanoparticles into cells. Upon sonicating and filtrating cells, we obtained lysates which, mixed with Au or Ag nanoparticles, yield stable and repeatable SERS spectra, whose overall profile depends on the metal used as substrate, but not on the buffer used for the lysis process. Bands appearing in these spectra were shown to arise mostly from the cytosol and were assigned to adenine, guanine, adenosine and reduced glutathione (GSH). Spectral differences among various cell types also demonstrated that this approach is suitable for cell type identification.

ACS Style

E. Genova; Marco Pelin; G. Decorti; G. Stocco; Valter Sergo; A. Ventura; A. Bonifacio. SERS of cells: What can we learn from cell lysates? Analytica Chimica Acta 2018, 1005, 93 -100.

AMA Style

E. Genova, Marco Pelin, G. Decorti, G. Stocco, Valter Sergo, A. Ventura, A. Bonifacio. SERS of cells: What can we learn from cell lysates? Analytica Chimica Acta. 2018; 1005 ():93-100.

Chicago/Turabian Style

E. Genova; Marco Pelin; G. Decorti; G. Stocco; Valter Sergo; A. Ventura; A. Bonifacio. 2018. "SERS of cells: What can we learn from cell lysates?" Analytica Chimica Acta 1005, no. : 93-100.

Journal article
Published: 06 November 2017 in Toxicology Letters
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Azaspiracids (AZAs) are marine algal toxins that can be accumulated by edible shellfish to cause a foodborne gastrointestinal poisoning in humans. In the European Union, only AZA1, −2 and −3 are currently regulated and their concentration in shellfish is determined through their toxic equivalency factors (TEFs) derived from the intraperitoneal lethal potency in mice. Nevertheless, considering the potential human exposure by oral route, AZAs TEFs should be calculated by comparative oral toxicity data. Thus, the acute oral toxicity of AZA1, −2 and −3 was investigated in female CD-1 mice treated with different doses (AZA1: 135–1100 μg/kg; AZA2 and AZA3: 300–1100 μg/kg) and sacrificed after 24 h or 14 days. TEFs derived from the median lethal doses (LD50) were 1.0, 0.7 and 0.5, respectively for AZA1, −2 and −3. In fact, after 24 h from gavage administration, LD50s were 443 μg/kg (AZA1; 95% CL: 350−561 μg/kg), 626 μg/kg (AZA2; 95% CL: 430−911 μg/kg) and 875 μg/kg (AZA3; 95% CL: 757−1010 μg/kg). Mice dead more than 5 h after the treatment or those sacrificed after 24 h (doses: ≥175 μg AZA1/kg, ≥500 μg AZA2/kg and ≥600 μg AZA3/kg) showed enlarged pale liver, while increased serum markers of liver alteration were recorded even at the lowest doses. Blood chemistry revealed significantly increased serum levels of K+ ions (≥500 mg/kg), whereas light microscopy showed tissue changes in the gastrointestinal tract, liver and spleen. No lethality, macroscopic, tissue or haematological changes were recorded two weeks post exposure, indicating reversible toxic effects. LC–MS/MS analysis of the main organs showed a dose-dependency in gastrointestinal absorption of these toxins: at 24 h, the highest levels were detected in the stomach and, in descending order, in the intestinal content, liver, small intestine, kidneys, lungs, large intestine, heart as well as detectable traces in the brain. After 14 days, AZA1 and AZA2 were still detectable in almost all the organs and intestinal content.

ACS Style

M. Pelin; J. Kilcoyne; C. Nulty; S. Crain; P. Hess; A. Tubaro; S. Sosa. Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, −2 and −3 in mice. Toxicology Letters 2017, 282, 136 -146.

AMA Style

M. Pelin, J. Kilcoyne, C. Nulty, S. Crain, P. Hess, A. Tubaro, S. Sosa. Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, −2 and −3 in mice. Toxicology Letters. 2017; 282 ():136-146.

Chicago/Turabian Style

M. Pelin; J. Kilcoyne; C. Nulty; S. Crain; P. Hess; A. Tubaro; S. Sosa. 2017. "Toxic equivalency factors (TEFs) after acute oral exposure of azaspiracid 1, −2 and −3 in mice." Toxicology Letters 282, no. : 136-146.

Journal article
Published: 01 September 2017 in Chemico-Biological Interactions
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To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity.Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by Trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival. Statistical significance was determined by analysis of variance.Azathioprine and mercaptopurine had a significant time-dependent cytotoxic effect (p-value ANOVA = 0.012), with a viable cell count compared to controls of 55.5% and 67.5% respectively after 48 h and 23.7% and 36.1% after 96 h; no significant difference could be observed between the two drugs. Quantification of thiopurine metabolites evidenced that the most abundant metabolite was TIMP, representing 57.1% and 40.3% of total metabolites after 48 and 96 h. Total thiopurine metabolites absolute concentrations decreased over time: total mean content decreased from 469.9 pmol/million cells to 83.6 pmol/million cells (p-value ANOVA = 0.0030). However, considering the relative amount of thiopurine metabolites, TGMP content significantly increased from 11.4% cells to 26.4% (p-value ANOVA = 0.017). A significant association between thiopurine effects on viable cell counts could be detected only for MeTIMP: lower MeTIMP concentrations were associated with lower cell survival (p-value ANOVA = 0.011). Moreover, the ratio between MeTIMP and TGMP metabolites directly correlated with cell survival (p-value ANOVA = 0.037).Detailed quantification of thiopurine metabolites in a human hepatocytes model provided useful insights on the association between thioguanine and methyl-thioinosine nucleotides with cell viability.

ACS Style

Marco Pelin; Elena Genova; Laura Fusco; Monzer Marisat; Ute Hofmann; Diego Favretto; Marianna Lucafò; Andrea Taddio; Stefano Martelossi; Alessandro Ventura; Gabriele Stocco; Matthias Schwab; Giuliana Decorti. Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay. Chemico-Biological Interactions 2017, 275, 189 -195.

AMA Style

Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti. Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay. Chemico-Biological Interactions. 2017; 275 ():189-195.

Chicago/Turabian Style

Marco Pelin; Elena Genova; Laura Fusco; Monzer Marisat; Ute Hofmann; Diego Favretto; Marianna Lucafò; Andrea Taddio; Stefano Martelossi; Alessandro Ventura; Gabriele Stocco; Matthias Schwab; Giuliana Decorti. 2017. "Pharmacokinetics and pharmacodynamics of thiopurines in an in vitro model of human hepatocytes: Insights from an innovative mass spectrometry assay." Chemico-Biological Interactions 275, no. : 189-195.