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E-cigarettes induce toxicological effects that can raise the cancer risk. The contribute of EPR radical trapping technique
No full textE-cigarettes induce toxicological effects that can raise the cancer
risk. The contribute of EPR radical probe technique
Donatella Canistro1, Fabio Vivarelli1, Silvia Cirillo1, Andrea Sapone1, Moreno Paolini1,
Paola Franchi2, Marco Lucarini2
1Department of Pharmacy and Biotechnology (University of Bologna, Via Irnerio 48, I-40126 Bologna, Italy)
2Department of Chemistry “G. Ciamician” (University of Bologna, Via San Giacomo 11, I-40126 Bologna, Italy)
E-mail: [email protected]
Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution rather than smoke and without tobacco combustion. Perceived as a safer alternative to conventional cigarettes, e-cigs are aggressively marketed as lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory guidelines. Despite the burgeoning worldwide consumption of e-cigs, their safety remains largely unproven and it is unknown whether these devices cause in vivo toxicological effects
that could contribute to cancer. Here we illustrate the contribute of EPR radical probe technique in a study where it was possible to demonstrate the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat lung model. It was found that e-cig have a powerful booster effect on phase-I carcinogen-bioactivating enzymes, and increase oxygen free radical production and DNA oxidation.
We are able to indirectly evaluate the content of reactive oxygen species (ROS) in lungs tissues of exposed rats, by using an appropriate hydroxylamine that in the presence of transient radical species gives rise to a persistent nitroxide radical. (see Scheme 1)
Scheme 1
We found a significant increase of radical species production in samples of lungs tissues from exposed rats compared to samples from non-exposed animals.
[1] Canistro, D.; Vivarelli, F.; Cirillo, S.; Babot Marquillas, C.; Buschini, A.; Lazzaretti, M.;Marchi, L.; Cardenia, V.; Rodriguez-Estrada, M.T.; Lodovici, M.; Cipriani, C.; Lorenzini, A.; Croco, E.; Marchionni, S.; Franchi, P.; Lucarini, M.; Longo, V.; Della Croce, C.M.; Vornoli, A.; Colacci, A.; Vaccari, M.; Sapone, A.; Paolini, M. SCIENTIFIC REPORTS. 2017, DOI:10.1038/s41598-017-02317-8
[2] Vivarelli, F.; Canistro, D.; Franchi, P.; Sapone, A.; Vornoli, A.; Della Croce, C.; Lucarini, M.; Paolini, M. Life Sciences, 2016, 145, 166-173. DOI:10.1016/j.lfs.2015.12.033
[3] Fabbri, R.; Sapone, A.; Paolini, M.; Vivarelli, F.; Franchi, P.; Lucarini, M.; Pasquinelli, G.; Vicenti, R.; Macciocca, M.; Venturoli, S.; Canistro, D. Hystology and Hystopatology, 2015, 30, 725-730 DOI: 10.14670/HH-30.72
E-cigarettes induce toxicological effects that can raise the cancer risk. A frame from drug-metabolism and antioxidant homeostasis
No full textE-CIGARETTES INDUCE TOXICOLOGICAL EFFECTS THAT CAN RAISE THE CANCER RISK. A FRAME
FROM DRUG-METABOLISM AND ANTIOXIDANT HOMEOSTASIS.
1)Canistro D. 2)Vivarelli F. 3)Cirillo S. 4)Cardenia V. 5)Rodriguez-estrada MT.
Dept of Pharmacy and Biotechnology, Unibo
Electronic cigarettes (e-cigs) are devices designed to deliver nicotine in a vaping solution without tobacco combustion. Perceived as a safer alternative to conventional cigarettes, e-cigs are aggressively marketed as lifestyle-choice consumables, thanks to few restrictions and a lack of regulatory guidelines. Despite the burgeoning worldwide consumption of e-cigs, their safety remains largely unproven and it is unknown whether these devices cause in vivo toxicological effects that could contribute to cancer occurrence.
In the present study, we investigated the co-mutagenic and cancer-initiating effects of e-cig vapour in a rat model. To explore whether e-cigs induce toxicological effects, such as those involving cytochrome P450 (CYP) changes, we analyzed the modulation of carcinogen metabolizingenzymes in the lung of rats exposed to e-cig vapour. We observed a significant increase in CYP1A1/2 (activating, for example, polychlorinated biphenyls, aromatic amines, dioxins and PAHs), CYP2B1/2 (activating olefins and halogenated hydrocarbons), 2C11 (activating nitrosamines and mycotoxins) and CYP3A (activating hexamethyl phosphoramide and nitrosamines) documented by the sharp rise in the corresponding probes.
Conversely, we observed that the antioxidant enzymes catalase, DT-diaphorase and glutathione peroxidase and the conjugating phase II glutathione S-transferases, mainly involved in xenobiotic detoxification, were noticeable decreased, whereas UDP-glucuronyl-transferase was substantially unchanged.
Extrapolated to humans, the corresponding boosted CYP-linked monooxygenases together with reduced activity of antioxidant and detoxifying machinery would predispose a subject to an enhanced cancer risk from the widely bioactivated e-cig vapour procarcinogens associated with an increased risk of lung cancer
Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.
No full textDevelopment of microparticles for oral administration of the non-conventional radical scavenger
IAC and testing in an inflammatory rat model
1)Cirillo S.. 2)Paolini M.. 3)Vivarelli F.. 4)Passerini N.. 5)Albertini B.. 6)Di sabatino M. 7)Corace G.. 8)Luppi B..
9)Canistro D..
University of Bologna
The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC) is an innovative nonconventional
radical scavenger used with success in several disease models, such as inflammation,
neurological disorders, hepatitis and diabetes. To date, the main limit for the drug use is
represented by the intraperitoneal (i.p.) route of administration used in the pharmacological
treatments. In order to develop a delivery system that allowed both oral administration and the
therapeutic efficacy, Solid Lipid Microparticles (SLMs) containing a theoretical 18% w/w of IAC
have been produced. Recently, three formulations (A, B, C) have been tested at different dosages
in an inflammation and pain rat model. Inflammatory model was induced by the use of an
intraplantar injection of 100ml/paw of Freund's complete adjuvant (FCA). Administered per os at
different dosages, IAC B (60% stearic acid-20% Compritol® HD5 ATO) was the most efficient
formulation in reducing oedema and alleviating pain, compared to the gold standard Paracetamol.
Since the anti-diabetic effects of the i.p. formulation of IAC was already demonstrated in vivo, we
are now investigating the therapeutic efficacy of the selected (B) oral IAC formulation (SLMs) in
streptozotocin-nicotinamide diabetic mice
Effects of electronic cigarette vapors exposure on oxidative damage and antioxidant status
No full textEffects of electronic cigarette vapors exposure on oxidative damage and antioxidant status.
1)Bigagli E. 2)Canistro D. 3)Paolini M. 4)Vivarelli F. 5)Cirillo S. 6)Lodovici M. 1)Neurofarba, University of florence, Florence, Italy 2)Farmacia e biotecnologie, University of bologna, Bologna, Italy 3)Farmacia e biotecnologie, University of bologna, Bologna, Italy 4)Farmacia e biotecnologie, University of bologna, Bologna, Italy 5)F
Electronic cigarettes (e-cigs) are devices designed to deliver nicotine without burning tobacco and therefore, they are perceived as a safer alternative to the conventional cigarettes. However, because of the high temperature reached by e-cig solutions (> 200 C°) many toxic substances, including polycyclic aromatic hydrocarbons, formaldehyde, nitrosamines, metals and carbonyls can be generated. Very few in vivo animal studies have been conducted so far, most of them based on short-term e-cig exposure.
The aim of this study was therefore to evaluate the influence of e-cigs on oxidative stress related parameters, classical markers associated to conventional cigarette toxicity.
Male Sprague Dawley rats (8 weeks of age), were housed in an inhalation chamber and exposed either to e- cig vapors (1 mL/day of e-liquid containing 18 mg/mL of nicotine) or to a saline solution. One cycle of treatment consisted in 17 sec puff, 6 sec on, 5 sec off, 6 sec on, followed by 20 minutes stop. e-cigs voltage was set at 5.5. Animals were submitted to 11 cycles/ day for 5 consecutive days/week, for 4 consecutive weeks. At sacrifice, liver, kidneys, lungs, bladder and plasma were collected for the analysis of protein (carbonyl residues) and DNA oxidative damage (8-hydroxy-2’-deoxyguanosine (8-OHdG)) and of the total antioxidant power (FRAP assay).
At lung level, we found that FRAP values of rats exposed to e-cigs vapors were markedly reduced compared to controls. A similar trend was observed in the plasma, even if the statistical significance was not reached. Plasma FRAP levels and carbonyl residues were inversely correlated in e-cig exposed rats but not in controls. We also found that 8-OHdG markedly increased in the lung of e-cig vapor exposed rats compared to controls. An inverse correlation between FRAP levels and 8-OHdG in lung tissue from exposed animals was also observed.
These results demonstrate that e-cig vapor causes DNA oxidative damage and impairs antioxidant defenses in rats; given that these toxicological outcomes are typically induced by conventional cigarettes smoking, further investigations to better identify harmful e-cig effects especially in the long term, are of paramount importance
The prediction of protein secondary structure with a cascade correlation learning architecture of neural networks
No full textA Cascade Correlation Learning Architecture (CCLA) of neural networks is tested on the task of predicting the secondary structure of proteins. The results are compared with those obtained with Neural Networks (NN) trained with the back-propagation algorithm (BPNN) and generated with genetic algorithms. CCLA proceeds towards rite global minimum of the error function more efficiently than BPNN. However; only a slight improvement in the average efficiency value is noticeable (61.82% as compared with 61.61% obtained with BPNN). The values of the three correlation coefficients for the discriminated secondary structures are also rather similar (C-alpha, and C-beta and C-coil are 0.36, 0.29 and 0.36 with CCLA, and 0.36, 0.31 and 0.35 with BPNN). This indicates that the efficiency of the prediction does not depend upon the training algorithm, and confirms our previous observation that when single sequences are used as input code to the network system
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Anticancer potential of allicin: A review
Full text linkPhytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product
The chemopreventive effects of isothiocyanate moringin isolated from Moringa oleifera seeds.
No full textThe chemopreventive effects of isothiocyanate moringin isolated from Moringa oleifera seeds
1)Vivarelli F. 2)Paolini M. 3)Michl C. 4)Rascle A. 5)Weigl J. 6)De nicola G. 7)Iori R. 8)Cirillo S. 9)Canistro D.
University of Bologna
Over the past years, there has been a growing interest in the natural constituents of vegetables as
a potential means of cancer control. Isothiocyanates (ITCs) are considered as ideal
chemopreventive agents, due to their abundance in easily accessible brassica vegetables, their
ability to target multiple pathways involved in cancer aetiology coupled with a favourable
toxicological profile. Recently it was reported that sulphoraphane (SFN) inhibits STAT5-mediated
transcription. STAT5 (Signal Transducer and Activator of transcription 5) belongs to a family of
transcription factors (STAT1-6) mainly present in an inactive form in the cytoplasm of numerous
cell types and which are activated by phosphorylation in response to specific cytokines hormones
and growth factors. STAT5 plays a key role in the control of cell proliferation and survival, via the
regulation of genes such as c-Myc, Pim-1, Bcl-x, Osm or Cis and it also contributes to immune cell
differentiation and function. Its activity is normally tightly controlled, and is hence frequently
found deregulated in cancer where it is often constitutively activated. For these reasons STAT
inhibitors are considered as potential candidates for cancer prevention or therapy. Beside SFN,
more recently the isothiocyanate moringin (GMG-ITC), isolated from the Moringa oleifera, has
caught the interest of scientific community for its anti-inflammatory activity through the inhibition
of the NF-κ B pathway and it showed interesting anti cancer effects against mouse multiple
myeloma and human astrocytoma cell line. However, till now, very little is known about the
activity of GMG-ITC on cell signaling pathways.
The present study was conceived to explore the potential inhibitory effect of GMG-ITC on crucial
pathways commonly up-regulated in cancer, such as JAK/STAT and NF-κB comparing results with
those obtained with SFN. Results showed how SFN and GMG-ITC were able to suppress IL-3-
induced expression of STAT5 target genes in mouse pro-B cells, however, GMG-ITC reported a
stronger inhibitory activity compared to SFN. Both GMG-ITC and SFN did not inhibit STAT5
phosphorylation, suggesting a downstream inhibitory event. Expression of interferon (IFNα)-
stimulated STAT1/STAT2 target genes (G1P3, ISG15, STAT1, IRF9) in HeLa cells were downregulated
by GMG-ITC and SFN without altering STAT1 and STAT2 phosphorylation. Also in this
case GMG-ITC exhibited a more marked activity then those observed with SFN. Notable, basal
expression of c-Myc remained unaffected upon treatment with up to 10 μM SFN or GMG-ITC,
indicating that both ITCs inhibit STAT5-induced but not basal c-Myc. GMG-ITC and SFN had a
limited effect on IFNα-induced STAT1 and STAT2 activity, indicating that both ITCs differentially
target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar
range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. TNF-induced expression
of IL-8 and IL-6 was inhibited by both SFN and GMG-ITC, but this last appeared to be more
effective. Interestingly, SFN and GMG-ITC inhibit NF-κ B signaling with a greater potency than that
mediated by the well-known NF-κB inhibitor curcumin. As a whole, our data indicate how GMGITC
could be considered as a potent inhibitor of STAT5, NF-κ B as well as STAT1/STAT2 signaling
pathways, often overcoming the effects obtained with SFN. Given the implication of these
pathways in the carcinogenesis, inflammatory diseases and immune disorders, GMG-ITC could
represent a newsworthy and attractive chemopreventive agent
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