1,721,192 research outputs found
Effetti tossici delle tossine degli animali terrestri.
No full textI tossinologi generalmente distinguono gli animali velenosi da quelli tossici. Il termine animale velenoso viene attribuito a quelle creature capaci di produrre veleno da una ghiandola secernente fortemente sviluppata o da un gruppo di cellule e, quindi, di inoculare la tossina tramite un morso o un pungiglione. Sono invece considerati tossici quegli animali i cui tessuti, in parte o interamente, sono tali. Questi animali non hanno un meccanismo o una struttura per inoculare i loro veleni: l’intossicazione avviene tramite ingestione. In tutte le specie animali, inclusi gli uccelli, vi sono animali velenosi o tossici. Sono distribuiti ampiamente in tutto il regno animale, dal protista unicellulare Alexandrium (Gonyaulax) fino a certi mammiferi, l’ornitorinco e il topo ragno dalla coda corta.
Si contano almeno 400 specie di serpenti pericolosi per l’uomo e numerosissime specie di artropodi tossici e velenosi. Inoltre, si conoscono circa 1500 specie di animali marini tossici, presenti in quasi tutti i mari e gli oceani.
Il veleno può avere una o più funzioni nel sistema di difesa dell’animale: un ruolo d’attacco, come nella cattura e digestione del cibo, o di difesa dell’animale, per proteggersi da predatori ed aggressori. Può anche svolgere entrambe le funzioni. Il serpente usa principalmente il veleno per assicurarsi il cibo. A questo proposito, il veleno rappresenta un mezzo più efficace rispetto a velocità, dimensioni, forza, capacità di nascondersi o altre caratteristiche dei serpenti non velenosi. Il veleno, inoltre, gioca un ruolo nell’atteggiamento di difesa. I ragni velenosi usano la tossina per paralizzare la loro preda prima di estrarne l’emolinfa ed i liquidi corporei. Scopo primario del veleno non è, quindi, uccidere la preda, ma immobilizzarla. Lo stesso può essere detto degli scorpioni, sebbene questi non utilizzino il veleno per scopi difensivi. Nei pesci, quali i pesci scorpione e i pesci pietra, e negli elasmobranchi, quale la razza, l’apparato velenifero è usato per la difesa dell’animale e non per assicurarsi il cibo, come indicato anche dall’analisi chimica e farmacologica del veleno stesso. I veleni usati in azioni d’attacco si trovano nel polo orale dell’animale, mentre quelli usati in azioni di difesa si trovano nel polo aborale oppure nei tessuti dermici, come nel caso della razza e dei pesci scorpione. Il veleno può inoltre essere una sostanza derivante dalla catena alimentare o un prodotto del metabolismo. Man mano che il veleno passa da un animale all’altro attraverso la catena alimentare, sempre più tossina viene ad accumularsi
Genotossicità
No full textÈ ormai riconosciuto che l’esposizione a particolari agenti chimici od a miscele complesse può portare allo sviluppo di cancro. Più recentemente, è stato postulato che composti in grado di indurre modificazioni ereditarie nell’uomo possano causare lo sviluppo di patologie nella progenie. Tali modificazioni hanno origine in seguito a danno al DNA e risultano in mutazioni. Queste consistono in alterazioni più o meno grandi del materiale genetico, che possono portare alla sospensione del prodotto genico, alla diminuzione o all’aumento della sua attività, alla perdita delle sue capacità funzionali oppure non avere conseguenze. Il principale obiettivo della Tossicologia Genetica è l’identificazione di quegli agenti che sono in grado di interagire con gli acidi nucleici e che inducono alterazioni nelle componenti genetiche. Nell’industria, tale informazione è di fondamentale importanza per limitare od eliminare l’esposizione individuale a composti mutageni e, nel caso di farmaci, per procedere lungo la complessa strada dello sviluppo, una volta accertato che i benefici derivanti dall’impiego della molecola siano nettamente superiori ai rischi
Key Genetic and Epigenetic Mechanisms in Chemical Carcinogenesis
No full textDNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved
Castanea Sativa Mill. bark extract exerts chemopreventive properties triggering extrinsic apoptotic pathway in Jurkat cells
No full textChemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts has grown due to their phytochemical content. Castanea Sativa Mill. (CSM) bark extracts showed to exert positive effect in the counteraction of chronic/degenerative diseases, therefore, we evaluated its potential chemopreventive effect.
Flow cytometry (FCM) analyses of Jurkat cells treated with CSM bark extract 0-500 μg/mL for 24-72h allowed to evaluate its cytotoxicity and ability to induce apoptosis. Moreover, to define if CSM bark extract was selective towards cancer cells, its cytotoxic and proapoptotic effect was evaluated in human lymphocytes (PBL) from healthy donors.
CSM bark extract induced apoptosis in Jurkat cells in a dose- and time- dependent manner by activating the extrinsic pathways as evidenced by the activation of caspae 8. Moreover, at 24h treatment IC50 resulted 304 and 128 μg/mL in PBL and Jurkat cells respectively. CSM bark extract resulted a partially selective chemopreventive agent thanks to its ability to induce apoptosis in cancer cells at concentrations lower than in non-transformed cells
Pharmacogenetics of tyrosine kinase inhibitors in gastrointestinal stromal tumor and chronic myeloid leukemia
No full textIntroduction: Gastrointestinal stromal tumors (GIST) and chronic myeloid leukemia (CML) are two tumor types deeply different from each other. Despite the differences, these disorders share treatment with tyrosine kinase inhibitor imatinib. Despite the success of imatinib, the response rates vary among different individuals and pharmacogenetics may play an important role in the final clinical outcome. Areas covered: In this review, the authors provide an overview of the pharmacogenetic literature analyzing the role of polymorphisms in both GIST and CML treatment efficacy and toxicity. Expert opinion: So far, several polymorphisms influencing the pharmacokinetic determinants of imatinib have been identified. However, the data are not yet conclusive enough to translate pharmacogenetic tests in clinical practice. In this context, the major obstacles to pharmacogenetic test validation are represented by the small sample size of most studies, ethnicity and population admixture as confounding source, and uncertainty related to genetic variants analyzed. In conclusion, a combination of different theoretical approaches, experimental model systems and statistical methods is clearly needed, in order to appreciate pharmacogenetics applied to clinical practice in the near future
A molecular epidemiological approach to health risk assessment of urban air pollution
No full textThe ambient air of urban centres is polluted with potentially toxic chemicals mostly arising from the combustion or fuels used for transport. Among these compounds, benzene raises particular concern due to its haematoxicity and leukaemogenic risks. Although limits of benzene in air have been established in the European Union (5 microg/m(3)), individual exposure levels--and therefore risk estimates--cannot merely be extrapolated from environmental concentrations. Molecular epidemiology can facilitate health risk assessment by investigating the relationship between exposure to environmental pollutants and quantification of biomarkers that lie on the pathway of carcinogenesis upstream of clinical disease. We review the available for biomarker studies regarding health risks linked to environmental benzene exposure, and make some suggestions for future work
Sulforaphane as a promising molecule for fighting cancer
No full textCancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis. A great variety of phytochemicals have been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage. Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, in carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its potential therapeutic benefit in clinical settings. Overall, SFN appears to be an effective and safe chemopreventive molecule and a promising tool to fight cancer
Flow cytometry vs optical microscopy in the evaluation of the genotoxic potential of xenobiotic compounds
No full textBackground: It is now recognized that mutational events play a key role in the development of pathological processes like cancer, cardiovascular, and neurodegenerative disease. Therefore, it is crucial to have Genetics Toxicology tests that allow rapid and accurate identification of the mutagenic potential of a xenobiotic. Currently the most widely used technique is the "In vitro mammalian cell micronucleus test" performed by optical microscopy, but some problems have been highlighted, including the number of cells analyzed, the high subjectivity of the reading at the microscope and the long analysis times. Aim: The aim of this work was to develop a study protocol, for the automation of the "In vitro mammalian cell micronucleus test", by flow cytometry (FCM) analysis, to overcome the limits that afflict the optical microscopy. Methods: The study was conducted on peripheral blood lymphocytes treated with three known clastogens and three known aneugens. Results: The results obtained by the proposed FCM technique compared with those obtained through the validated method, demonstrated that the increase of micronuclei percentage is perfectly comparable between the two methods. Conclusions: This fact, in view of results supported by a high number of cells analyzed and obtained by an accurate and objective reading, with a considerable reduction of the analysis time, can support a future request for validation of the micronucleus analysis by FCM
Isothiocyanates Are Promising Compounds against Oxidative Stress, Neuroinflammation and Cell Death that May Benefit Neurodegeneration in Parkinson's Disease
Full text linkParkinson's disease (PD) is recognized as the second most common neurodegenerative disorder and is characterized by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the mechanisms involved in neuronal loss are not completely understood yet; however, misfolded proteins, oxidative stress, excitotoxicity and inflammation play a pivotal role in the progression of the pathology. Neuroinflammation may have a greater function in PD pathogenesis than initially believed, taking part in the cascade of events that leads to neuronal death. To date, no efficient therapy, able to arrest or slow down PD, is available. In this context, the need to find novel strategies to counteract neurodegenerative progression by influencing diseases' pathogenesis is becoming increasingly clear. Isothiocyanates (ITCs) have already shown interesting properties in detoxification, inflammation, apoptosis and cell cycle regulation through the induction of phase I and phase II enzyme systems. Moreover, ITCs may be able to modulate several key points in oxidative and inflammatory evolution. In view of these considerations, the aim of the present review is to describe ITCs as pleiotropic compounds capable of preventing and modulating the evolution of PD
Sulforaphane from Cruciferous Vegetables: Recent Advances to Improve Glioblastoma Treatment
Full text linkSulforaphane (SFN), an isothiocyanate (ITC) derived from cruciferous vegetables, particularly broccoli and broccoli sprouts, has been widely investigated due to its promising health-promoting properties in disease, and low toxicity in normal tissue. Although not yet fully understood, many mechanisms of anticancer activity at each step of cancer development have been attributed to this ITC. Given the promising data available regarding SFN, this review aimed to provide an overview on the potential activities of SFN related to the cellular mechanisms involved in glioblastoma (GBM) progression. GBM is the most frequent malignant brain tumor among adults and is currently an incurable disease due mostly to its highly invasive phenotype, and the poor efficacy of the available therapies. Despite all efforts, the median overall survival of GBM patients remains approximately 1.5 years under therapy. Therefore, there is an urgent need to provide support for translating the progress in understanding the molecular background of GBM into more complex, but promising therapeutic strategies, in which SFN may find a leading role
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