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Enrico Sabbioni

Publications and source records attributed to Enrico Sabbioni.

At least 19 recordsLinked to original sources
PubMed2006

Metabolism of arsenic in Drosophila melanogaster and the genotoxicity of dimethylarsinic acid in the Drosophila wing spot test.

Inorganic arsenic is nongenotoxic in the Drosophila melanogaster wing somatic mutation and recombination test (SMART). Recent evidence in mammalian systems indicates that methylated metabolites of arsenic are more genotoxic than inorganic arsenic. Thus, we hypothesized that inorganic arsenic is nongenotoxic in Drosophila because they are unable to biotransform arsenic to methylated forms. In the present study, we fed trivalent and pentavalent inorganic arsenic to Drosophila larvae and adults and measured the production of methylated derivatives. No biomethylated arsenic species were found in the organisms or in the growth medium, which suggests that Drosophila are unable to biomethylate inorganic arsenic. Exposure of Drosophila to the methylated arsenic derivative dimethylarsinic acid (DMA(V)) resulted in incorporation of this organoarsenic compound without demethylation. In addition, we used the SMART wing spot assay, which measures loss of heterozygosity (LOH) resulting from gene mutation, chromosomal rearrangement, chromosome breakage, and chromosome loss, to evaluate the genotoxicity of DMA. DMA by itself induced significant increases in the frequency of total spots, small spots, and large single spots. These results are consistent with the important role of arsenic biomethylation as a determinant of the genotoxicity of arsenic compounds. The absence of biomethylation in Drosophila could explain the lack of genotoxicity for inorganic arsenic and the genotoxicity of methylated arsenic species in the SMART wing spot assay.

Animals↗
PubMed2006

Comparison of impedance-based sensors for cell adhesion monitoring and in vitro methods for detecting cytotoxicity induced by chemicals.

The recent European Commission REACH (Registration, Evaluation and Authorisation of Chemicals) policy outlines a plan for toxicological testing by using alternative non-animal in vitro methods. In this context, there is a need to develop and standardise high-throughput screening (HTS) methods for studying the cytotoxicity induced by chemicals. Electrochemical impedance spectroscopy (EIS) can be considered as a complementary technique to alternative in vitro testing for studying cell adhesion to the substrate, and can give real-time and kinetic information on cell responses to a toxicant. This paper describes the development of a home-made chip based on impedance spectroscopy, and its application in studying the kinetics of BALB/3T3 cell adhesion and the cellular responses to a toxic product as a function of time. Concentrations of sodium arsenite, ranging from 10 microM up to 1000 microM, were tested in the system, and the results were compared with those obtained with standard protocols used to study basal cytotoxicity induced by chemicals in the BALB/3T3 cell line. The results show that the sensitivity of the developed chip was better than that with the MTT test, with the additional advantages of online monitoring.

Animals↗
PubMed2005

Carcinogenicity.

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Animal Testing Alternatives↗
PubMed2005

Blast from the past: the aluminum's ghost on the lanthanum salts.

Hyperphosphatemia is a common serious complication of chronic renal diseases, which needs appropriate continuous treatment in order to avoid ominous side effects. Therefore, oral chelating agents able to avoid phosphate absorption by the gut are mandatory. In the past, Aluminium salts, and more recently Calcium and Magnesium salts, and a synthetic resin polyallylamine hydrochloride have been employed, but Aluminium was later abandoned, because it has been a silent killer of many uremic patients, due to subtle absorption eventually leading to toxicity on Central Nervous System and bone, with allucinations, seizures, dementia, and osteomalacia, bone pain, fracturing osteodystrophy, and death. Recently, a new chelating agent able to bind dietary phosphate, namely Lanthanum carbonate has been introduced, with a proven efficacy profile for short-term treatment. However, after careful examination of the very few scientific papers available to date, we strongly advise caution before adopting, at present, lanthanum carbonate as a phosphate binder in uremic patients. In fact, notwithstanding minimized, some data are worrying: first, Lanthanum ions are absorbed, though at a minimal extent, by human gut; 2) pharmacokinetic evaluations show a greater exposure to Lanthanum in uremic patients;3) Lanthanum concentration is increased tenfold in blood and fivefold in bone after short-term supplementation in uremic patients; 4) there is no proofs that Lanthanum cannot cross the blood brain barrier in uremic patients; 5)Lanthanum has many biological effects and is potentially highly toxic. The Aluminum story should serve as cautionary tale when considering the use of new metal ions.

Area Under Curve↗
PubMed2004

Transmural distribution of iron in the hypoxic and reoxygenated rabbit left ventricular myocardium.

Transmural distribution of low molecular weight iron (LMWI), total iron, and protein carbonyls (PC) was investigated in the perfused rabbit heart under aerobic conditions, and after 60 min hypoxia followed or not by 3 min reoxygenation. In the aerobic perfused hearts, LMWI, total iron and PC did not show significant transmural differences. Hypoxia increased LMWI and PC levels, which were significantly higher in the subendocardium than in the subepicardium; further significant changes were not observed after reoxygenation. Total iron showed no transmural difference and was not significantly affected by both hypoxia and reoxygenation. Free iron was undetectable in the myocardial effluent of all experimental groups. Thus, hypoxia favors myocardial iron decompartmentalisation and oxidative stress, which are significantly greater in the inner than in the outer ventricular layers. Such findings may add further insight into the problem of the vulnerability of the mammalian subendocardium to injury induced by oxygen deprivation.

Animals↗
PubMed2004

In vitro DNA damage by arsenic compounds in a human lymphoblastoid cell line (TK6) assessed by the alkaline Comet assay.

Arsenic is classified as a carcinogen for humans, but as a possible genotoxic agent. Thus, taking into account the controversial data about how arsenic compounds are able to induce genetic damage, we investigated the possible genotoxic activity of different arsenic compounds in the TK6 human lymphoblastoid cell line using the alkaline Comet assay. Eight different inorganic and organic arsenical compounds have been selected as follows: three inorganic (sodium arsenite, sodium arsenate and sodium hexafluorarsenate) and five organic (monomethylarsonic and dimethylarsinic acids, arsenobetaine, tetramethylarsonium iodide and tetraphenylarsonium chloride). According to their toxicity and genotoxicity, the highest concentration tested was 10 mM, and the duration of the treatments was 30 min or 3 h. The results indicate that some compounds belonging to both the organic and inorganic species were able to induce significant increases in the tail moment, the parameter used to determine genotoxicity. Thus, the inorganic compounds sodium arsenite and sodium arsenate (but not sodium hexafluoroarsenate) were genotoxic, while among the organoarsenic species tested only tetramethylarsonium iodide and tetraphenylarsonium chloride compounds (but not monomethylarsonic, dimethylarsinic acids and arsenobetaine) induced significant increases in the tail moment. Nevertheless, genotoxic induction was generally only observed at the highest doses tested.

Arsenates↗
PubMed2004

A modular approach to the ECVAM principles on test validity.

The European Centre for the Validation of Alternative Methods (ECVAM) proposes to make the validation process more flexible, while maintaining its high standards. The various aspects of validation are broken down into independent modules, and the information necessary to complete each module is defined. The data required to assess test validity in an independent peer review, not the process, are thus emphasised. Once the information to satisfy all the modules is complete, the test can enter the peer-review process. In this way, the between-laboratory variability and predictive capacity of a test can be assessed independently. Thinking in terms of validity principles will broaden the applicability of the validation process to a variety of tests and procedures, including the generation of new tests, new technologies (for example, genomics, proteomics), computer-based models (for example, quantitative structure-activity relationship models), and expert systems. This proposal also aims to take into account existing information, defining this as retrospective validation, in contrast to a prospective validation study, which has been the predominant approach to date. This will permit the assessment of test validity by completing the missing information via the relevant validation procedure: prospective validation, retrospective validation, catch-up validation, or a combination of these procedures.

Animal Testing Alternatives↗
PubMed2004

In vitro effects of platinum compounds on lymphocyte proliferation and cytokine release.

In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those used in cancer treatment were studied. Spontaneous and PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) and in vitro release of TNF-alpha, IFN-gamma, and IL-5 were assessed in presence of high and very low concentrations of Pt salts: 10(-4) and 10(-7) M (NH4)2[PtCl6], (NH4)2[PtCl4], PtCl4, PtCl2, Na2PtI6, and cis-diaminedichloroPt (CisPt). Spontaneous and PHA-stimulated PBMC proliferation were both inhibited by 10(-4) M (NH4)2[PtCl6] and (NH4)2[PtCl4], while only PHA-stimulated proliferation was inhibited by 10(-4) M CisPt, without significant effects of the other Pt salts. TNF-alpha release from PBMC was reduced by 10(-4) M (NH4)2[PtCl6] and INF-gamma release was reduced by 10(-4) and 10(-7) M hexa- and tetrachloroplatinate and 10(-4) M Na2PtI6, but not by other Pt salts. IL-5 release (related to the Th2 immune response) was inhibited by 10(-4) M (NH4)2[PtCl6], (NH4)2[PtCl4] and Na2PtI6, but it was enhanced by both 10(-4) and 10(-7) M PtCl4. PtCl2 did not influence the immune effects. The study shows Pt salts have immune effects and their potency is ranked in the following order: (NH4)2[PtCl6] > (NH4)2[PtCl4] > Na2PtI6 and CisPt > PtCl4 > PtCl2. These results indicate that certain Pt salts affect lymphocyte proliferation and cytokine release. The intracellular mechanisms responsible for such effects have not been identified.

Adult↗
PubMed2004

Different effects of platinum, palladium, and rhodium salts on lymphocyte proliferation and cytokine release.

The effects of graded concentrations of Pt, Pd, and Rh salts on spontaneous and PHA-stimulated peripheral blood mononuclear cell (PBMC) proliferation and IFN-gamma, TNF-alpha, and IL-5 release were the focus of this study. Spontaneous PBMC proliferation was inhibited by all 10(-4) M salts (with the exception of PtCl2), while it was enhanced by 10(-5) M PtCl2 as well as by 10(-5) and 10(-6) M (NH4)2[RhCl6] and RhCl3 (but not by 10(-7) M salts). Pt, Pd, and Rh compounds showed similar effects on PHA-stimulated PBMC proliferation and cytokine release; however, the effects on IFN-gamma release were stronger. Thus, 10(-4) and 10(-5) M (NH4)2[PtCl6] and 10(-4) M (NH4)2[PtCl4] inhibited the PHA-stimulated immune activity; 10(-4) M PtCl2 did not exert activity, while 10(-6) M (NH4)2[PtCl6] and 10(-5) and 10(-6) M (NH4)2[PtCl4] and PtCl2 enhanced PBMC proliferation and/or cytokine release. (NH4)2[PdCl6] showed stronger dose-related inhibitory effects (present also at 10(-7) M concentration) on PHA-stimulated proliferation and cytokine release than (NH4)2[PdCl4], PdCl2, or Rh salts; the inhibitory activity of (NH4)2[RhCl6] was slightly higher than that of RhCl3. In conclusion, this study shows that: (a) the immune capacity of Pt, Pd, and Rh depends on speciation; (b) low concentrations of Pt salts stimulate spontaneous and PHA-stimulated immune responses; (c) the in vitro activity of Pd compounds (which are only inhibitory) is higher than that of Pt and Rh salts. These findings are consistent with the observations that sensitization and allergic contact dermatitis in response to Pd are increased in the general population, although the roles of cross-sensitization to Pd and Ni are difficult to determine.

Adult↗
PubMed2003

Influence of metal ions on gene expression of BALB 3T3 fibroblasts.

It is widely recognized that metal compounds may modify gene expression. In this context, we have searched for genes whose expression may be affected by cadmium and platinum ions within the context of a cell culture system. Cadmium is well known for its carcinogenic potential while platinum is destined to become more and more interesting because of its increasing use in the automotive industries. By applying differential display to cultures of mouse fibroblast, we have identified two transcripts (acute lymphoblastic leukemia-1, All-1, and a novel gene named metal-responsive gene, MERE-1) that were responsive to platinum and cadmium ions. Moreover, further experiments with a panel of metal compounds have shown that MERE-1 was strongly induced also by La(NO3)2 and Cr(NO3)3, and to a lesser extent, by Na2CrO4 and (NH4)2TeCl6.

Animals↗
PubMed2003

Platinum toxicity and gene expression in Xenopus embryos: analysis by FETAX and differential display.

Since the level of platinum in the environment is destined to increase, because of its use in vehicle catalytic converters, the toxicity of platinum needs further investigation. In this study, the frog embryo teratogenesis assay-Xenopus (FETAX) was used to compare the embryotoxicity and teratogenicity of two common platinum species, (NH4)2PtCl4 and (NH4)2PtCl6. The uptake rates of the two platinum species were studied, and also their effects on the expression of genes encoding metallothionein and heat-shock protein 70, which are known to be induced by several stress factors. In addition, the differential display technique was used to search for genes that were specifically induced by platinum. A gene for the type I collagen alpha-chain and a novel gene were identified.

Abnormalities, Drug-Induced↗
PubMed2003

ECVAM's response to the changing political environment for alternatives: consequences of the European Union chemicals and cosmetics policies.

The European Centre for the Validation of Alternative Methods (ECVAM) has restructured its services by directly targeting the animal tests that need to be replaced. In view of the short time-lines for making available and implementing validated methods, ECVAM is offering to steer the process by bringing together the inputs of stakeholders and encouraging the early involvement of regulators. In essence, steering groups formed by ECVAM senior staff, and complemented with external experts, will carry out the project management and will coordinate the various inputs.

Administration, Topical↗
PubMed2003

Effects of resveratrol on lymphocyte proliferation and cytokine release.

Resveratrol, synthesized in dietary plants and contained in wine, has been reported to play a beneficial role in certain cardiovascular regulatory mechanisms and to inhibit carcinogenesis by activating immune and inflammatory responses and apoptosis. The object of this study was to elucidate the "in vitro" effects of different concentrations of resveratrol (10(-4), 10(-5), and 10(-7) M) on human peripheral blood mononuclear cell (PBMC) proliferation and cytokine release. Spontaneous PBMC proliferation was unaffected by resveratrol, while the compound at 10(-4) M inhibited (69%) the PHA-stimulated PBMC proliferation. The proliferation stimulation index (ie, the ratio of PHA-stimulated PBMC proliferation/spontaneous PBMC proliferation) of cultures containing 10(-4) M resveratrol was very low in relation to the control, while the proliferation stimulation index values at 10(-5) and 10(-7) M were similar and slightly higher (without statistical significance), respectively. At 10(-4) M, resveratrol strongly inhibited PHA-stimulated IFN-gamma and TNF-alpha release from PBMC, but it did not cause inhibition at 10(-5) or 10(-7) M. The concomitant immune effects of resveratrol on PBMC proliferation and release of IFN-gamma and TNF-alpha may be explained by an inhibitory effect on transcription factor NF-kappaB. This study suggests that resveratrol, which is typically present in red wine at about 10(-5) M, is unlikely to cause inhibitory immune effects. However, a stimulatory effect of low concentrations of resveratrol on the immune system cannot be excluded.

Adult↗