Antonia Lucisano

Effect of fumonisin B1 on structure and function of macrophage plasma membrane

Fumonisin B1 (FB1), a mycotoxin produced by Fusarium moniliforme and related fungi, is nephrotoxic, neurotoxic, hepatotoxic, carcinogenic and immunosuppressive in animals and man. In this study we evaluate the modifications of fluidity, endocytosis and peroxidative damage of plasma membrane induced by FB1 in macrophage cell line J774A.1. In these immune cells FB1 (1-10 microM) enhances membrane fluidity and increases, time-dependently, the horseradish peroxidase (HRP) endocytosis. This effect is concentration-dependent, significant at 10 microM, and reverted by IFN-gamma (100 U/ml). Moreover, FB1 (1-10 microM) induces a membrane peroxidative damage as evident by the increase of malondialdehyde (MDA) production. All these mycotoxin effects provide additional insight into potential mechanism by which FB1, in macrophages, might enhance membrane damage and oxidative stress contributing to the pathogenesis of mycotoxin induced diseases.

Effect of fumonisin B1 on inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated J774A.1 cells

Fumonisin B1 (FB1) is a water-soluble fungal metabolite that elicits a wide spectrum of toxicological effects. Cellular targets of FB1 include immune cells and in particular macrophages. In the present study the cytotoxic effect of FB1 (1-100 microM) was evaluated using a murine macrophage cell line (J774A.1) as model system. The effect of FB1 on nitric oxide (NO) and prostaglandin E2 (PGE2) production induced by lipopolysaccharide (LPS, 10 and 100 ng/ml) was also investigated. Macrophages were pretreated with FB1 for 72 h and then stimulated with LPS for 24 h. The increase of LPS-induced production of these inflammatory mediators was observed at increasing concentrations of FB1 (0.1-10 microM) and was found to be concentration dependent. By western blot analysis we demonstrated that the observed increase of NO and PGE2 production by FB1 was related to an enhancement of iNOS and COX-2 expression.

Ochratoxin A affects COS cell adhesion and signaling

Ochratoxin A (OTA), a metabolite produced by strains of Aspergillus and Penicillium, has nephritogenic, carcinogenic, and teratogenic activity in animals and humans. Nanomolar concentrations of OTA promote apoptosis in a cell-type specific fashion. In this study, we have analyzed the molecular mechanism by which OTA affects COS cell adhesion and signaling resulting in an apoptotic response. OTA, at noncytotoxic doses, was able to detach collagen- and fibronectin-adherent cells from immobilized substratum. However, prior to inducing detachment of adherent cells, OTA caused apoptosis as measured by caspase-3 activation. The treatment of adherent cells by OTA caused a reduction of tyrosine phosphorylation levels of FAK and of the adapter protein paxillin. The down-regulation of FAK preceded apoptosis and cell detachment induced by OTA. The mycotoxin was also able to cause a decrease of the phosphorylation levels of the two Shc isoforms, P66 and P52, in adherent cells. Since these Shc isoforms have been implicated in the activation of protein kinase c-Src, which is required for FAK tyrosine phosphorylation, the observed dephosphorylation of FAK and of the FAK substrate paxillin by OTA could be ascribed to the early down-regulation of Shc isoforms. However, whether FAK and Shc phosphorylation contribute both to the same pathway leading to the induction of apoptosis by OTA or are involved in two parallel signaling pathways remains to be investigated.

METAL CONCENTRATIONS IN THE LIVER AND KIDNEY OF RAPTOR SPECIES FROM THE CALABRIA REGION, ITALY

We have focused our study on the concentrations of non essential trace metals Pb, Cd and Cr and essential heavy metals Zn and Cu, in the liver and kidney of raptor species from different areas of the Calabria region in Italy, with the aim of obtaining information concerning the quality and the contamination level of their habitat. No significant differences related to sampling areas and gender were found, while significant differences were found in metal concentrations among species. Mean Cd concentrations in the kidneys were generally 1.5-10 fold higher than hepatic ones, while Pb was mostly concentrated in the liver; a different pattern in tissue Cr concentration was observed between species. Referring to essential metals, Cu levels were higher in the liver, whereas higher Zn concentrations were constantly present in the kidneys. The ratio between kidney and liver metal concentrations (K:Ls) was also evaluated. The measured concentrations in toxic elements can be considered as indicative of chronic exposure to low amounts of pollutants. The essential metal concentrations were in the range of physiological values and did not show the presence of any deficiency or excess of metal. The present study can be considered as a starting point in the study of a possible correlation between levels of pollutants and the appearance of any adverse effects in raptor species in the Calabria area.

Trace metal concentration in wild avian species from Campania, Italy

AbstractThis study was conducted to determine heavy metals concentrations in tissues of 94 birds belonging to different species from coastal areas of Naples and Salerno (Southern Italy) in order to provide baseline data concerning trace element levels in wild birds living in or close to an area characterized by high anthropogenic impact. Additional aim of this study was to verify if diet influenced metal accumulation, so birds were classified as birds of prey, fish eating birds and insectivorous birds.Kidney was the primary organ for Cd accumulation in all groups considered, Pb was accumulated preferentially in bone, whereas Hg showed high values in liver of fish eating birds. Zn showed the highest mean concentrations, while Cu levels were one order of magnitude less. The variance analysis with respect to feeding habits disclosed only a lower accumulation of Hg in insectivores with respect to the other groups. For all metals, the concentrations measured in tissues should be considered indicative of chronic exposure to low, “background” environmental levels and/or to the presence of low bioavailable metals in the environment. In addition, metal levels were not of toxicological concern, being always well below the toxic thresholds defined for each metal.