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  1. Article ; Online: Is the mushroom Meripilus giganteus a potential cancer chemopreventive agent?

    Lenzi, Monia / Gasperini, Sofia

    Phytotherapy research : PTR

    2023  Volume 38, Issue 3, Page(s) 1170–1172

    MeSH term(s) Humans ; Agaricales ; Polyporales ; Neoplasms
    Language English
    Publishing date 2023-04-22
    Publishing country England
    Document type Letter
    ZDB-ID 639136-9
    ISSN 1099-1573 ; 0951-418X
    ISSN (online) 1099-1573
    ISSN 0951-418X
    DOI 10.1002/ptr.7856
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  2. Article ; Online: Genotoxicity Evaluation of The Novel Psychoactive Substance MTTA.

    Lenzi, Monia / Gasperini, Sofia / Corli, Giorgia / Marti, Matteo / Hrelia, Patrizia

    International journal of molecular sciences

    2023  Volume 24, Issue 13

    Abstract: MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In ... ...

    Abstract MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test". To consider the in vitro effects of both the parental compound and the related metabolites, TK6 cells were treated with MTTA in the absence or presence of an exogenous metabolic activation system (S9 mix) for a short-term time (3 h) followed by a recovery period (23 h). No statistically significant increase in the MNi frequency was detected. Specifically, in the presence of S9 mix, only a slight increasing trend was observable at all tested concentrations, whereas, without S9 mix, at 75 µM, almost a doubling of the negative control was reached. For the purposes of comprehensive evaluation, a long-term treatment (26 h) was also included. In this case, a statistically significant enhancement in the MNi frequency was observed at 50 µM.
    MeSH term(s) Animals ; Micronucleus Tests/methods ; Mutagens/toxicity ; Mutagens/metabolism ; DNA Damage ; Central Nervous System Agents ; Mutagenicity Tests/methods ; Mammals/metabolism
    Chemical Substances Mutagens ; (5-methoxy-2-thienyl)thioacetic acid (58386-00-8) ; mephtetramine ; Central Nervous System Agents
    Language English
    Publishing date 2023-06-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241310498
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  3. Article ; Online: Anthraquinones: Genotoxic until Proven Otherwise? A Study on a Substance-Based Medical Device to Implement Available Data for a Correct Risk Assessment.

    Cocchi, Veronica / Gasperini, Sofia / Lenzi, Monia

    Toxics

    2022  Volume 10, Issue 3

    Abstract: A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The "In Vitro Mammalian Cell Micronucleus Test" was performed on human TK6 cells by flow ... ...

    Abstract A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The "In Vitro Mammalian Cell Micronucleus Test" was performed on human TK6 cells by flow cytometry. Cultures were treated with concentrations of SMD tested in the range of 0-2 mg/mL for short treatment time (3 h) both in the absence and presence of an exogenous metabolic activation system, followed by a recovery period in fresh medium (23 h) and for extended treatment time (26 h) without an exogenous metabolic activation system. At the end of both treatment times, cytotoxicity, cytostasis, apoptosis and micronuclei (MNi) frequency were analysed in treated cultures and then compared with those measured in concurrent negative control cultures. The SMD did not induce a statistically significant increase MNi frequency under any of experimental conditions tested. The negative outcome shows that the SMD is non-mutagenic in terms of its ability to induce chromosomal aberrations both in the absence and presence of an exogenous metabolic activation system. The study ended by analyzing intracellular ROS levels to exclude the pro-oxidant ability, typically linked to DNA damage. On the contrary, our results demonstrated the ability the SMD to counteract oxidative stress.
    Language English
    Publishing date 2022-03-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2733883-6
    ISSN 2305-6304 ; 2305-6304
    ISSN (online) 2305-6304
    ISSN 2305-6304
    DOI 10.3390/toxics10030142
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  4. Article: Antimutagenicity and Antioxidant Activity of

    Gasperini, Sofia / Greco, Giulia / Angelini, Sabrina / Hrelia, Patrizia / Fimognari, Carmela / Lenzi, Monia

    Pharmaceutics

    2023  Volume 15, Issue 10

    Abstract: ... Castanea ... ...

    Abstract Castanea sativa
    Language English
    Publishing date 2023-10-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15102465
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  5. Article: Antimutagenic and Chemopreventive Properties of 6-(Methylsulfinyl) Hexyl Isothiocyanate on TK6 Human Cells by Flow Cytometry.

    Cocchi, Veronica / Hrelia, Patrizia / Lenzi, Monia

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 1242

    Abstract: 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present ... ...

    Abstract 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), is the main bioactive compound present in
    Language English
    Publishing date 2020-08-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.01242
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  6. Article ; Online: Genotoxicological Characterization of (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and Their Association.

    Lenzi, Monia / Gasperini, Sofia / Cocchi, Veronica / Tirri, Micaela / Marti, Matteo / Hrelia, Patrizia

    International journal of molecular sciences

    2022  Volume 23, Issue 10

    Abstract: The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still ... ...

    Abstract The novel psychoactive substance (NPS) 4-Methyl-5-(4-methylphenyl)-4,5-dihydroxazol-2-amine (4,4'-DMAR) shows psychostimulant activity. Data on the acute toxicity of 4,4'-DMAR are becoming increasingly available, yet the long-term effects are still almost unknown. In particular, no data on genotoxicity are available. Therefore, the aim of the present study was to evaluate its genotoxic potential using the "In Vitro Mammalian Cell Micronucleus Test" (MNvit) on (±)cis-4,4'-DMAR and (±)trans-4,4'-DMAR and their associations. The analyses were conducted in vitro on human TK6 cells. To select suitable concentrations for MNvit, we preliminarily evaluated cytotoxicity and apoptosis. All endpoints were analysed by flow cytometry. The results reveal the two racemates' opposite behaviours: (±)cis-4,4'-DMAR shows a statistically significant increase in micronuclei (MNi) frequency that (±)trans-4,4'-DMAR is completely incapable of. This contrast confirms the well-known possibility of observing opposite biological effects of the cis- and trans- isomers of a compound, and it highlights the importance of testing single NPSs that show even small differences in structure or conformation. The genotoxic capacity demonstrated stresses an additional alarming toxicological concern related to this NPS. Moreover, the co-treatments indicate that consuming both racemates will magnify the genotoxic effect, an aspect to consider given the unpredictability of illicit drug composition.
    MeSH term(s) Animals ; Central Nervous System Stimulants/pharmacology ; Humans ; Illicit Drugs/pharmacology ; Isomerism ; Mammals ; Oxazoles/pharmacology
    Chemical Substances Central Nervous System Stimulants ; Illicit Drugs ; Oxazoles ; para-methyl-4-methylaminorex (18Y239214S)
    Language English
    Publishing date 2022-05-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23105849
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  7. Article ; Online: 6-(Methylsulfonyl) Hexyl Isothiocyanate: A Chemopreventive Agent Inducing Autophagy in Leukemia Cell Lines.

    Cocchi, Veronica / Jávega, Beatriz / Gasperini, Sofia / O'Connor, José-Enrique / Lenzi, Monia / Hrelia, Patrizia

    Biomolecules

    2022  Volume 12, Issue 10

    Abstract: Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged ... ...

    Abstract Autophagy is a fundamental catabolic process of cellular survival. The role of autophagy in cancer is highly complex: in the early stages of neoplastic transformation, it can act as a tumor suppressor avoiding the accumulation of proteins, damaged organelles, and reactive oxygen species (ROS), while during the advanced stages of cancer, autophagy is exploited by cancer cells to survive under starvation. 6-(Methylsulfonyl) hexyl isothiocyanate (6-MITC) is the most interesting compound in the Wasabia Japonica rizhome. Recently, we proved its ability to induce cytotoxic, cytostatic, and cell differentiation effects on leukemic cell lines and its antimutagenic activity on TK6 cells. In the current study, to further define its chemopreventive profile, Jurkat and HL-60 cells were treated with 6-MITC for 24 h. The modulation of the autophagic process and the involvement of ROS levels as a possible trigger mechanisms were analyzed by flow cytometry. We found that 6-MITC induced autophagy in Jurkat and HL-60 cells at the highest concentration tested and increased ROS intracellular levels in a dose-dependent manner. Our results implement available data to support 6-MITC as an attractive potential chemopreventive agent.
    MeSH term(s) Humans ; Reactive Oxygen Species ; Cytostatic Agents/pharmacology ; Isothiocyanates/pharmacology ; Leukemia/drug therapy ; Autophagy ; HL-60 Cells ; Apoptosis ; Cell Line, Tumor
    Chemical Substances 6-(Methylsulfinyl)hexyl isothiocyanate ; Reactive Oxygen Species ; Cytostatic Agents ; isothiocyanic acid (3129-90-6) ; Isothiocyanates
    Language English
    Publishing date 2022-10-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom12101485
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  8. Article ; Online: The Genotoxicity of Acrylfentanyl, Ocfentanyl and Furanylfentanyl Raises the Concern of Long-Term Consequences.

    Gasperini, Sofia / Bilel, Sabrine / Cocchi, Veronica / Marti, Matteo / Lenzi, Monia / Hrelia, Patrizia

    International journal of molecular sciences

    2022  Volume 23, Issue 22

    Abstract: Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). ... ...

    Abstract Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property. The ability to induce structural and numerical chromosomal aberrations in human lymphoblastoid TK6 cells was evaluated by employing the flow cytometric protocol of the in vitro mammalian cell micronucleus test. Our study demonstrated the non-genotoxicity of Fentanyl, i.e., the pharmaceutical progenitor of the class, while its illicit non-pharmaceutical analogues were found to be genotoxic. In particular, Acrylfentanyl led to a statistically significant increase in the MNi frequency at the highest concentration tested (75 μM), while Ocfentanyl and Furanylfentnyl each did so at both concentrations tested (150, 200 μM and 25, 50 μM, respectively). The study ended by investigating reactive oxygen species (ROS) induction as a possible mechanism linked to the proved genotoxic effect. The results showed a non-statistically significant increase in ROS levels in the cultures treated with all molecules under study. Overall, the proved genotoxicity raises concern about the possibility of serious long-term consequences.
    MeSH term(s) Humans ; Reactive Oxygen Species ; Fentanyl/toxicity ; DNA Damage
    Chemical Substances acrylfentanyl (T64K7YD33B) ; furanyl fentanyl (3F7C9J1LS7) ; Reactive Oxygen Species ; Fentanyl (UF599785JZ)
    Language English
    Publishing date 2022-11-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms232214406
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  9. Article: Naxitamab Activity in Neuroblastoma Cells Is Enhanced by Nanofenretinide and Nanospermidine.

    Galassi, Lucrezia / Rossi, Martina / Lodeserto, Pietro / Lenzi, Monia / Borsetti, Francesca / Voltattorni, Manuela / Farruggia, Giovanna / Blasi, Paolo / Orienti, Isabella

    Pharmaceutics

    2023  Volume 15, Issue 2

    Abstract: Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven ... ...

    Abstract Neuroblastoma cells highly express the disialoganglioside GD2, a tumor-associated carbohydrate antigen, which is also expressed in neurons, skin melanocytes, and peripheral nerve fibers. Immunotherapy with monoclonal anti-GD2 antibodies has a proven efficacy in clinical trials and is included in the standard treatment for children with high-risk neuroblastoma. However, the strong neuro-toxicity associated with anti-GD2 antibodies administration has hindered, until now, the possibility for dose-escalation and protracted use, thus restraining their therapeutic potential. Strategies to increase the efficacy of anti-GD2 antibodies are actively sought, with the aim to enable chronic treatments that could eradicate minimal residual disease and subsequent relapses, often occurring after treatment. Here, we report that Nanofenretinide and Nanospermidine improved the expression of GD2 in neuroblastoma cells (CHP-134) and provided different effects in combination with the anti-GD2 antibody naxitamab. In particular, Nanofenretinide significantly increased the cytotoxic effect of naxitamab while Nanospermidine inhibited cell motility at extents proportional to naxitamab concentration. In neuroblastoma cells characterized by a low and heterogeneous basal expression of GD2, such as SH-SY5Y, which may represent the cell heterogeneity in tumors after chemotherapy, both Nanofenretinide and Nanospermidine increased GD2 expression in approximately 50% of cells, thus shifting the tumor population towards improved sensitivity to anti-GD2 antibodies.
    Language English
    Publishing date 2023-02-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527217-2
    ISSN 1999-4923
    ISSN 1999-4923
    DOI 10.3390/pharmaceutics15020648
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  10. Article ; Online: Evaluation of Cytotoxic and Mutagenic Effects of the Synthetic Cathinones Mexedrone, α-PVP and α-PHP.

    Lenzi, Monia / Cocchi, Veronica / Gasperini, Sofia / Arfè, Raffaella / Marti, Matteo / Hrelia, Patrizia

    International journal of molecular sciences

    2021  Volume 22, Issue 12

    Abstract: Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present ... ...

    Abstract Mexedrone, α-PVP and α-PHP are synthetic cathinones. They can be considered amphetamine-like substances with a stimulating effect. Actually, studies showing their impact on DNA are totally absent. Therefore, in order to fill this gap, aim of the present work was to evaluate their mutagenicity on TK6 cells. On the basis of cytotoxicity and cytostasis results, we selected the concentrations (35-100 µM) to be used in the further analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by flow cytometry. Mexedrone demonstrated its mutagenic potential contrary to the other two compounds; we then proceeded by repeating the analyzes in the presence of extrinsic metabolic activation in order to check if it was possible to totally exclude the mutagenic capacity for α-PVP and α-PHP. The results demonstrated instead the mutagenicity of their metabolites. We then evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the highlighted effects but the results did not show a statistically significant increase in ROS levels for any of the tested substances. Anyway, our outcomes emphasize the importance of mutagenicity evaluation for a complete assessment of the risk associated with synthetic cathinones exposure.
    MeSH term(s) Alkaloids/toxicity ; Apoptosis/drug effects ; Cell Death/drug effects ; Cell Line ; Cell Survival/drug effects ; Humans ; Methamphetamine/analogs & derivatives ; Methamphetamine/toxicity ; Micronucleus, Germline/drug effects ; Micronucleus, Germline/metabolism ; Mutagens/toxicity ; Pentanones/toxicity ; Pyrrolidines/toxicity ; Reactive Oxygen Species/metabolism
    Chemical Substances Alkaloids ; Mutagens ; Pentanones ; Pyrrolidines ; Reactive Oxygen Species ; alpha-pyrrolidinohexanophenone ; mexedrone ; Methamphetamine (44RAL3456C) ; cathinone (540EI4406J) ; 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (767K3AWA4R)
    Language English
    Publishing date 2021-06-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22126320
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