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Histamine (HIS) intoxication is a poisoning caused by histamine in food. Cheese is one of the most common dairy products associated with histamine levels, varying depending on the processing methods. The final content of histamine in cheese is influenced by intrinsic and extrinsic factors, their interactions, and contamination stem ming from food processing. The application of control measures may be useful to inhibit/reduce production during cheese manufacture and processing but have a limited effect. To reduce histamine intoxication outbreaks from cheese consumption the introduction of quality control programs and appropriate risk mitigation options should be applied along the dairy chain from an overall perspective of food safety based on individual susceptibility and consumer sensitivity. As key food safety, this topic should be considered in future regulations in dairy products because the lack of a clear law on HIS limits in cheese may result in a significant potential deviation from the EU food safety strategy.

Bisphenol A (BPA) as a chemical hazard may enter the milk chain during primary production at the farm and, successively, during milk processing at a dairy company. To identify the potential pathways that play a role in the occurrence of BPA, a monitoring model for risk assessment based on the identification of the hazards at each stage of milk processing was investigated. Milk samples were analyzed using liquid chromatography with fluorescence detection. Quantifiable levels were detected in samples obtained from the raw milk storage tank, pasteurized milk from the storage tank, and packaged milk. The highest BPA contamination levels were detected in raw milk from the storage tank (mean 0.265 µg/L). Despite the fact that dietary exposure levels were below the temporary daily intake, BPA may have adverse effects, particularly for vulnerable population groups. New monitoring programs involving each stage of milk processing should therefore be applied.

Micro- and nanoplastics (MPs/NPs) are among the most widely distributed pollutants in the environment. It has been suggested that exposure to MPs/NPs can trigger toxicity pathways among which inflammation and oxidative stress (OS) play a pivotal role. Once absorbed, MPs/NPs may act locally or access the bloodstream and, following the translocation process, reach several organs and tissues, including the gonads. Notably, MPs/NPs can bioaccumulate in human and murine placenta, opening new scenarios for toxicological evaluations. We review recent studies on the effects of MPs/NPs on the reproductive health in aquatic and terrestrial organisms of both sexes, focusing on the role of OS and the antioxidant defence system failure as the main underlying mechanisms. Alterations in gametogenesis, embryonic and offspring development, and survival have been shown in most studies and often related to a broken redox balance. All these detrimental effects are inversely related to particle size, whereas they are closely linked to shape, plastic polymer type, superficial functionalization, concentration, and time of exposure. To date, the studies provide insights into the health impacts, but no conclusions can be drawn for reproduction toxicity. The main implication of the few studies on antioxidant substances reveals their potential role in mitigating MP-induced toxic effects.

The occurrence of analogues of bisphenol A (BPA), including bisphenol F(BPF) in milk is still not well known. BPF may enter the milk chain at the farm and during milk processing at the dairy company. This study identified the main BPF contamination pathways using a monitoring model based on the identification of the hazard at three stages along the dairy chain: raw milk from the storage tank, pasteurized milk from the storage tank, and cardboard packaged milk. Quantitative analysis was performed by high-performance liquid chromatography with fluorometric detection (HPLC/FD) system. BPF was detected in all analysed stages (fromLOQ to 2.686 μg/L). The structural and toxicological similarity between BPF and BPA suggested considering both bisphenols for a more comprehensive risk evaluation. The daily intake of BPF and of the sum of BPF and BPA, and the worst-case scenario through the consumption of packaged milk were calculated. Exposure levels below the temporary daily intake, fixed for only BPA, were detected in all consumer age classes. Nevertheless, the use of BPA substitutes represents a risk to human health because of their potential synergic effects. The application of a monitoring program at each stage of milk processing at the dairy company may represent a useful strategy to ensure food safety in the milk chain.

Aim The study aimed at evaluating the concentration levels of organochlorine pollutants in donkey milk and their modulation on the intestinal strongyle infection. Risk evaluation for consumer health was also investigated. Methods We analyzed milk of grazing donkeys living in areas of Southern of Italy affected by organochlorine compounds environmental pollution and parasite infection. The presence of pollutants was assessed through summary statistics; regression analysis of intestinal strongyle on pollutant concentration was performed to investigate the relationship between the two variables. Results PCB concentrations (mainly non-dioxin-like (ndl)-PCBs) were higher than OCP ones. Mean values of ndl-PCBs across areas ranged from 93.13 to 263.64 ng g−1. In all sample units we detected the six indicator PCBs with the prevalence of the PCB 153, followed by the PCB 28 and the PCB 101. Among the dioxin-like (dl)-PCBs, non-ortho PCB 169, 77 and 126 were assessed in some milk samples; in all areas we detected the mono-ortho PCB 118 and PCB 105. Positive correlation between infection level and six indicator PCBs as well as between the former and HCB, on WW and LW, were observed (at least statistically significant at 5 percent). In some cases, Dl-PCB concentrations emerged as dangerous given the EU maximum residue limit for PCDD/Fs and dl-PCBs. Conclusion Evidence supports the hypothesis of an immunosuppressive role of organochlorine pollutants; risk evaluation reveals the potential health impact of dl-PCB intake, particularly for major donkey milk consumers such as infants, children with cow milk and multiple food intolerance, and elders.

Sodiumvalproate (VPA), an antiepileptic drug, may cause dose- and time-dependent hepatotoxicity. However, its iatrogenic molecular mechanism and the rescue therapy are disregarded. Recently, it has been demonstrated that sodium butyrate (NaB) reduces hepatic steatosis, improving respiratory capacity and mitochondrial dysfunction in obese mice. Here, we investigated the protective effect of NaB in counteracting VPA-induced hepatotoxicity using in vitro and in vivo models. Human HepG2 cells and primary rat hepatocytes were exposed to high VPA concentration and treated with NaB. Mitochondrial function, lipid metabolism, and oxidative stress were evaluated, using Seahorse analyzer, spectrophotometric, and biochemical determinations. Liver protection by NaB was also evaluated in VPA-treated epileptic WAG/Rij rats, receiving NaB for 6months. NaB prevented VPA toxicity, limiting cell oxidative and mitochondrial damage (ROS, malondialdehyde, SOD activity, mitochondrial bioenergetics), and restoring fatty acid oxidation (peroxisome proliferator-activated receptor α expression and carnitine palmitoyl-transferase activity) in HepG2 cells, primary hepatocytes, and isolated mitochondria. In vivo, NaB confirmed its activity normalizing hepatic biomarkers, fatty acid metabolism, and reducing inflammation and fibrosis induced by VPA. These data support the protective potential of NaB on VPA-induced liver injury, indicating it as valid therapeutic approach in counteracting this common side effect due to VPA chronic treatment.

Lines of evidence have shown the embryogenic and transgenerational impact of bisphenol A (BPA), an endocrine-disrupting chemical, on immune-metabolic alterations, inflammation, and oxidative stress, while BPA toxic effects in adult obese mice are still overlooked. Here, we evaluate BPA&rsquo, s worsening effect on several hepatic maladaptive processes associated to high-fat diet (HFD)-induced obesity in mice. After 12 weeks HFD feeding, C57Bl/6J male mice were exposed daily to BPA (50 &mu, g/kg per os) along with HFD for 3 weeks. Glucose tolerance and lipid metabolism were examined in serum and/or liver. Hepatic oxidative damage (reactive oxygen species, malondialdehyde, antioxidant enzymes), and mitochondrial respiratory capacity were evaluated. Moreover, liver damage progression and inflammatory/immune response were determined by histological and molecular analysis. BPA amplified HFD-induced alteration of key factors involved in glucose and lipid metabolism, liver triglycerides accumulation, and worsened mitochondrial dysfunction by increasing oxidative stress and reducing antioxidant defense. The exacerbation by BPA of hepatic immune-metabolic dysfunction induced by HFD was shown by increased toll-like receptor-4 and its downstream pathways (i.e., NF-kB and NLRP3 inflammasome) amplifying inflammatory cytokine transcription and promoting fibrosis progression. This study evidences that BPA exposure represents an additional risk factor for the progression of fatty liver diseases strictly related to the cross-talk between oxidative stress and immune-metabolic impairment due to obesity.

Bisphenol A (BPA) is a non-persistent anthropic and environmentally ubiquitous compound widely employed and detected in many consumer products and food items; thus, human exposure is prolonged. Over the last ten years, many studies have examined the underlying molecular mechanisms of BPA toxicity and revealed links among BPA-induced oxidative stress, male and female reproductive defects, and human disease. Because of its hormone-like feature, BPA shows tissue effects on specific hormone receptors in target cells, triggering noxious cellular responses associated with oxidative stress and inflammation. As a metabolic and endocrine disruptor, BPA impairs redox homeostasis via the increase of oxidative mediators and the reduction of antioxidant enzymes, causing mitochondrial dysfunction, alteration in cell signaling pathways, and induction of apoptosis. This review aims to examine the scenery of the current BPA literature on understanding how the induction of oxidative stress can be considered the “fil rouge” of BPA’s toxic mechanisms of action with pleiotropic outcomes on reproduction. Here, we focus on the protective effects of five classes of antioxidants—vitamins and co-factors, natural products (herbals and phytochemicals), melatonin, selenium, and methyl donors (used alone or in combination)—that have been found useful to counteract BPA toxicity in male and female reproductive functions.

The study compared the polycyclic aromatic hydrocarbons (PAH) profile of human milk collected from Italian mothers and different brands of infant formula available on Italian market. Levels of 14 PAHs most frequently occurred in food, PAH markers listed by Commission Regulation (EC) No. 1881/2006, and carcinogenic PAHs classified by the International Agency for Research on Cancer, were determined by high-pressure liquid chromatography with fluorescence detector. The average concentrations of total PAHs were 114.93 in breast milk and 53.68μgkg-1in infant formula. Furthermore, Benzo(a)pyrene (BaP) and the sum of ∑PAH4 markers (BaP, Chrysene, Benzo(a,h)anthracene and Benzo(b)fluoranthene) were higher than the permissible limit of 1μgkg-1in 43% and 86% for breast milk and in 10% and 76% for infant formula samples, respectively. Breast milk showed higher levels (P&nbsp

Several organochlorine compounds (OCs) were measured in European eels from the Tevere river (Italy). It followed that some of them are still important chemical contaminants. Concentrations of dichlorodiphenyltrichloroethanes (DDTs) are hazardous for the consumer health; those of the 6 indicator polychlorinated biphenyls (PCBs) are often close to the current European maximum residue limit and always higher than the former limit. The relationship between OC concentrations, biometric parameters and the lipid content was then investigated. A strong positive correlation with eel size emerged for the indicator PCBs and DDTs concentrations expressed on wet weight basis. This is explained by the corresponding higher lipid percentage that characterizes bigger eels and the absence of a dilution effect for compounds of main concerns. On the basis of the PCB-TDI threshold for a 70 kg person, we suggest that 1 should consume no more than 2 eels per week each weighing about 100 g. Thus, we conclude that eel consumption should be limited and restricted to eels relatively shorter and lighter.

Chemical hazards may enter the milk chain during primary production. The study, for the first time, investigated the occurrence of bisphenol A (BPA) levels in cow milk samples collected on the farm following manual or mechanical milking and from the cooling tank. We applied a new monitoring model based on the identification of the hazards at each stage of the milk chain to identify potential pathways for contamination along the milk chain. We evaluated exposure to BPA through milk consumption based on detected contamination levels and the temporary tolerable daily intake established by the European Food Safety Authority (EFSA). Milk samples (n = 72) were analyzed using liquid chromatography with fluorescence detection. The mean BPA concentrations were 0.757 µg/L in manually milked samples, 0.580 µg/L in mechanically milked samples, and 0.797 µg/L in milk from the cooling tank. Bisphenol A occurred in the milk chain as a result of different stages of milking, and reached the highest levels at the end of the milk chain. Although the dietary intake of BPA was below the EFSA's temporary tolerable daily intake, exposure to BPA, even at low doses, through milk consumption represents a public health concern. Therefore, to ensure milk safety, new monitoring plans should be applied based on the identification of hazards at each stage of the milk chain.

Diet represents the primary route for human exposure to bisphenol A (BPA). As endocrine disruptor (ED), BPA has raised concerns about its adverse effects on human health. Therefore, EFSA recommended a tolerable daily intake (t-TDI) of 4 µg/kg bw/day and the EU Regulation n. 2018/213 fixed a specific migration limit (SML) of 0.05 mg/kg for BPA in food from plastic materials intended to come in contact with food. Considering the widespread consumption of milk and milk products, the contamination of dairy products is a matter of public health concern. The aim of the study was to investigate the BPA contamination levels of raw cow’s milk from two farms located in Campania region, Italy. The milk samples (n.22), weekly collected from the cooling tank, were analyzed using liquid chromatography with fluorescence detection. In raw milk from both farms, preliminary results showed the occurrence of BPA levels lower than the SML limit, ranging from not detected to 2.34 µg/L. The consumer exposure calculated considering hypothetical raw milk consumption and three possible scenarios was below the t-TDI. BPA could be present in milk due to environmental contamination, and also as a result of the migration from contact materials used during milking and storage. Despite the low levels of exposure through milk consumption, low doses can have lasting effects during human development. Thus, new approaches, methods, and plans should be applied to monitor the ED contamination, such as BPA and other pollutants, and to assure milk safety.

Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) are persistent organic pollutants, associated with a range of adverse health effects, including interference with the immune system. In this study, we investigate the capability of NDL-PCBs 101, 153, and 180, 3 of the 6 NDL-PCBs defined as indicators, to impair the immune response in lipopolysaccharide (LPS)-activated J774A.1 and primary murine macrophages. Our results clearly demonstrate that the exposure of J774A.1 and primary macrophages to NDL-PCB 153 or 180 or all NDL-PCBs mixtures causes a significant reduction in LPS-induced cytokine/chemokine synthesis, such as tumor necrosis factor-α and interleukin-6, together with monocyte chemoattractant protein-1, involved in cell recruitment. Moreover, PCBs were found to suppress LPS-stimulated NO production, and to reduce cyclooxygenase-2 and inducible nitric oxide synthase expression in J774A.1 and primary macrophages. At mechanistic level, PCBs significantly counteract the LPS-driven toll-like receptor (TLR) 4 and CD14 upregulation, therefore inhibiting downstream nuclear factor-κB (NF-κB) activation in J774A.1. Furthermore, PCBs determine a significant loss of macrophage endocytic capacity, a prerequisite for efficient antigen presentation. Taken together, these data indicate that NDL-PCBs reduce macrophage responsiveness, particularly when they are combined at concentrations per se inactive, impairing the capability to orchestrate a proper immune response to an infectious stimulus, disrupting TLR4/NF-κB pathway.

Aim The study aims at investigating whether, and if so, to what extent the strong presence of urban and industrial waste in a territory may cause PCB contamination in goat milk produced therein. Methods We compared PCB concentrations in goat milk from three different locations in the Campania region (Italy). One of the three locations, together with its surrounding area, has long suffered from illegal waste disposal and burning mainly by the so-called Ecomafia. The other locations, not involved in these illegal activities, allowed us to create a control group of goats with characteristics very similar to those of main interest. Results In milk from the waste contaminated area we identified high PCB concentrations (six indicator PCBs amounted to 170 ng g−1 on lipid weight, on average), whereas there was an almost total absence of such pollutants in milk from the control group. Concentrations of the six indicator PCBs were above the current European maximum residue limit fixed by the EU. At the same time, we found a lower average value of lipid content and a negative relationship between lipid content and PCB concentrations. Conclusion Evidence indicates the potential health risk for consumers living in areas involved in illegal dumping of waste.

The study compared the profile of 14 polycyclic aromatic hydrocarbons, frequently occurred in food, in milk (N=22) and meat/fish based (N=18) baby foods available on the Italian market. PAH total levels, markers (Regulation EC/835/2011) and carcinogenic PAHs were determined by high- performance liquid chromatography with fluorescence detector (HPLC-FD). The average of total PAHs was 52.25 μg kg-1 in milk and 11.82 μg kg-1 in meat/fish based baby foods. The levels of PAH markers were higher than the permissible EU limits of 1 μg kg-1 in 18.2% and 77.7 % milk, and 5.6% and 44.4 % meat/fish based baby foods. Milk based samples showed significant higher values (P < 0.05) of carcinogenic and possible carcinogenic hydrocarbons than meat/fish based products. The Margins of Exposure (MOE) value of milk based baby food samples indicated a potential concern for consumer health. Monitoring programs, and good agriculture and manufacture practices should be recommended.

To assess the potential impact of the industrial activity on food safety and risk for consumers, the aim of the study was to evaluate the levels of 14 polycyclic aromatic hydrocarbons (PAH) in 69 samples of wild and farm Mytilus galloprovincialis, collected in sites of coast of Gulf of Naples, Tyrrhenian Sea. All hydrocarbons were found in samples. Higher levels of pyrolytic PAHs were in wild than in farm mussels. Benzo(a)pyrene exceeded the Regulation (EC) n.835/11 levels of 1 μg/kg in 15 samples (71.42%) of wild and 25 samples (65.79%) of farm mussels. System of sum of 4 hydrocarbons exceeded the law level in 15 samples (71.42%) of wild and 21 samples (55.26%) of farm mussels. Wild mussel levels showed a potential impact of pyrolytic sources of PAH on food safety. Occurrence of carcinogenic PAHs should be a cause for concern, in areas where the mussels are being farmed for human consumption.

This 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.

Leptin and/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been used to evaluate, for the first time, the modification of leptin and ghrelin both at serum and tissue levels. In SHR, we evaluate plasma leptin level and tissue protein expression in both placenta and adipose tissue at the end of gestation (day 20) versus normotensive Wistar–Kyoto (WKY) animals. The expression of functional leptin receptor (Ob-Rb) in peripheral tissues and in the hypothalamus was evaluated. Moreover, we measured plasma ghrelin level and its mRNA expression in the stomach and placenta. SHR strain presented significantly lower plasma leptin levels when compared with those found in pregnant or not WKY controls. Interestingly, in the placenta, leptin gene expression was higher in SHR than normotensive WKY. Moreover, we demonstrated a resistance to the effects of leptin via ‘downregulation’ of hypothalamic receptors in pregnant SHR. Conversely, SHR presented significantly higher ghrelin plasma levels when compared with those found in pregnant or not WKY. However, we observed that ghrelin level in the stomach of SHR did not change during pregnancy, and on the opposite, mRNA ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a different production of this hormone in the fetal–placental unit. These data gain further insight into metabolic hormone modifications observed in a model of pre-existing hypertension associated with pregnancy.

Seven target polychlorinated biphenyls (PCBs; IUPAC nos. 28, 52, 101, 118, 138, 153, and 180) and the organochlorine pesticides (OCPs) hexachlorobenzene (HCB) and dichlorodiphenyltrichloroethane (DDT) and its related metabolites (p,p'-DDT, p,p'-DDE, and p,p'-DDD) were quantified in edible tissues from seven marine species (European hake, red mullet, blue whiting, Atlantic mackerel, blue and red shrimp, European flying squid, and Mediterranean mussel) from the Gulf of Naples in the southern Tyrrhenian Sea (Italy). PCBs 118, 138, and 153 were the dominant congeners in all the species examined. The concentrations of all PCBs (from not detectable to 15,427 ng g(-1) fat weight) exceeded those of all the DDTs (from not detectable to 1,769 ng g(-1) fat weight) and HCB (not detectable to 150.60 ng g(-1) fat weight) in the samples analyzed. The OCP concentrations were below the maximum residue limits established for fish and aquatic products by the Decreto Ministerale 13 May 2005 in all the samples analyzed; therefore the OCPs in the southern Tyrrhenian Sea species are unlikely to be a significant health hazard. Conversely, the mean concentrations of PCBs exceeded (greatly in some cases) the current limits (200 ng(-1) fat weight) set by the European Union for terrestrial foods. Although the manufacture and use of PCBs are banned or highly restricted, these compounds still are important persistent chemical contaminants in the Gulf of Naples.

Edible tissues from 10 marine species, collected from the Gulf of Naples in the Southern Tyrrhenian Sea (Italy) between February and July 2003, were analysed for the presence of organochlorine pesticides hexachlorobenzene (HCB) and DDTs (p,p′-DDT, p,p′-DDE, and p,p′-DDD), and 20 polychlorinated biphenyls (PCBs). The PCB levels (calculated as the sum of all the determined congeners) were found to be the highest (from 56.8 to 47909.5 ng/g on lipid basis), followed by the DDTs (sum of p,p′-DDT and its metabolites

Latest technological developments have allowed a more efficient use of the frequency spectrum, providing resources for the deployment of fourth generation broadband mobile networks, named LTE, in a portion of UHF band previously allocated to TV broadcasting. However, to cope with this new scenario, the designing criteria of the TV receiving installations need to be reviewed as well as, for existing installations, the problems of coexistence must to be addressed carefully. Accordingly, this study focuses on laboratory results of experimental tests carried out to evaluate interference effects occurring on DVB-T channels and in presence of different MATV configurations, due to radio emissions generated by LTE Base Stations in the 800 MHz band.

Non-dioxin-like polychlorinated biphenyls (NDL-PCBs) are highly lipophilic environmental contaminants that accumulate in lipid-rich tissues, such as adipose tissue. Here, we reported the effects induced by PCBs 101, 153 and 180, three of the six NDL-PCBs defined as indicators, on mature 3T3-L1 adipocytes. We observed an increase in lipid content, in leptin gene expression and a reduction of leptin receptor expression and signaling, when cells were exposed to PCBs, alone or in combination. These modifications were consistent with the occurrence of "leptin-resistance" in adipose tissue, a typical metabolic alteration related to obesity. Therefore, we investigated how PCBs affect the expression of pivotal proteins involved in the signaling of leptin receptor. We evaluated the PCB effect on the intracellular pathway JAK/STAT, determining the phosphorylation of STAT3, a downstream activator of the transcription of leptin gene targets, and the expression of SOCS3 and PTP1B, two important regulators of leptin resistance. In particular, PCBs 153 and 180 or all PCB combinations induced a significant reduction in pSTAT3/STAT3 ratio and an increase in PTP1B and SOCS3, evidencing an additive effect. The impairment of leptin signaling was associated with the reduction of AMPK/ACC pathway activation, leading to the increase in lipid content. These pollutants were also able to increase the transcription of inflammatory cytokines (IL-6 and TNFα). It is worthy to note that the PCB concentrations used are comparable to levels detectable in human adipose tissue. Our data strongly support the hypothesis that NDL-PCBs may interfere with the lipid metabolism contributing to the development of obesity and related diseases.

Several polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) investigated in soft tissues of the frequently monitored Mytilus galloprovincialis were compared to those of Ensis siliqua, a highly dispersed and economically important bivalve species, though rarely investigated. Overall PCBs had higher concentrations than OCPs in both species with a prevalence of tri- tetra-and penta-chlorinated biphenyls in E. siliqua and a prevalence of hexa- hepta and octa-chlorinated biphenyls in M. galloprovincialis. E. siliqua emerges as a suitable complement to mussels for monitoring PCBs and OCPs pollution.

Fumonisin B-1 (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 muM) was evaluated using a murine macrophage cell line (J774A.1) as model system. The effect of FB1 on nitric oxide (NO) and prostaglandin E-2 (PGE(2)) 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 10 muM) and was found to be concentration dependent. By western blot analysis we demonstrated that the observed increase of NO and PGE(2) production by FB1 was related to an enhancement of iNOS and COX-2 expression.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Insulin resistance (IR) appears to be critical in its pathogenesis. We evaluated the effects of sodium butyrate (butyrate) and its synthetic derivative N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) in a rat model of insulin resistance and steatosis induced by high-fat diet (HFD). METHODS: After weaning, young male Sprague-Dawley rats were divided into 4 groups receiving different diets for 6 weeks: 1. control group (standard diet); 2. HFD; 3. HFD plus butyrate (20 mg/kg/die) and 4. HFD plus FBA (42.5 mg/Kg/die, the equimolecular dose of butyrate). Liver tissues of the rats were analyzed by Western blot and real-time PCR. Insulin resistance, liver inflammation and Toll-like pattern modifications were determined. RESULTS: Evaluation of these two preparations of butyrate showed a reduction of liver steatosis and inflammation in HFD fed animals. The compounds showed a similar potency in the normalisation of several variables, such as transaminases, homeostasis model assessment for insulin resistance index, and glucose tolerance. Both treatments significantly reduced hepatic TNF-α expression and restored GLUTs and PPARs, either in liver or adipose tissue. Finally, FBA showed a higher potency in reducing pro-inflammatory parameters in the liver, via suppression of Toll-like receptors and NF-κB activation. CONCLUSIONS: Our results demonstrated a protective effect of butyrate in limiting molecular events underlying the onset of IR and NAFLD, suggesting a potential clinical relevance for this substance. In particular, its derivative, FBA, could represent an alternative therapeutic option to sodium butyrate, sharing a comparable efficacy, but a better palatability and compliance.

In this study the presence of residual levels of Polycyclic Aromatic Hydrocarbons (PAHs) in milk samples from Calabria was evaluated. A comparative analysis of PAHs concentrations was conducted on raw, pasteurized, UHT semi-skimmed and whole milk. Quantitative determination of PAHs was performed by HPLC using a fluorescence detector and analysis in HPLC-MS was conducted to confirm the presence of these compounds. Residual levels of PAHs were found in all milk samples analyzed, showing higher concentrations in pasteurized and UHT milk than in raw milk samples. The results obtained demonstrate that PAHs presence also in raw milk is dependent from environmental pollution but pasteurization and UHT treatments of milk can influence PAHs formation; the differences found between whole and semi-skimmed samples can be due to different fat content of milk. © 2011 Elsevier Ltd.

Non-dioxin-like polychlorinated biphenyls (PCBs) are stable and lipophilic chemicals that persist in the environment and tend to bioaccumulate in the food chains. In the present study, we have investigated the effect of PCBs 101, 153, and 180 on macrophage J774A.1 by assessing cell viability and apoptotic cell death. We have combined morphological techniques and biochemical ones to establish the relevance of apoptosis in macrophage cell death induced by PCBs, alone or in combination. Treatment with the examined PCBs caused the loss of cell viability and accelerated apoptosis in a concentration-dependent manner. Moreover, a synergistic effect on cell death and apoptosis was evidenced for all PCBs at concentrations which were inactive alone. The apoptosis induced by PCBs involved the increase of caspase-3 activity. Also, Bcl-2 and Bax proteins were assessed to elucidate the apoptosis machinery induced in macrophage cultures by PCBs. Our results indicate that the increase in PCB-induced apoptosis correlates with a reduction in the expression of antiapoptotic Bcl-2 and an increase in the expression of proapoptotic Bax. Interestingly, concentrations of PCBs inactive by themselves induce apoptosis when PCBs are combined. In conclusion, our findings suggest that, although less toxic than dioxin like congeners, the examined non-dioxin-like PCBs are equally dangerous as immunotoxic pollutants, also considering their presence as mixtures at higher levels than dioxin-like PCBs in biotic and abiotic matrices. © 2011 Elsevier Ireland Ltd.

Measuring organochlorine compounds in muscle tissue of European eels from the Garigliano River in Campania (Italy), overall PCBs emerged as the most abundant pollutants, followed by DDTs, Dieldrin and HCB. Target PCBs, IUPAC nos. 118, 138, 153 and 180, were the dominant congeners accounting for 64.2% of total PCBs. Among OCPs, p,p'-DDE was detected in all eels, always with higher concentration levels than other OCPs; p,p'-DDT was frequently detected, about 93.3% of the sample. The high and statistically significant correlations between concentration and length as well as weight of eels suggest that the organochlorine compounds concentrations tend to increase with the size and consequently with the age. Concentrations of DDTs and PCBs detected were similar to those reported in studies relative to France, UK and Sweden. As regards toxicological risk for human health, in general OCPs residual levels were below the limits established for fish and aquatic products. Conversely, the concentrations of PCBs exceeded the limit set by the EU for terrestrial foods. Our results imply that OCPs and PCBs are still important persistent chemical contaminants in Campania freshwaters, although their manufacture and use are banned or highly restricted.

Ochratoxin A (OTA) is a fungal metabolite with controversial immunomodulatory effects. A prolonged in vivo exposure to the mycotoxin may result in impaired immunity and decreased resistance to infections. In the present study, OTA modulation of lipopolysaccharide (LPS)-induced inflammatory process is described in the macrophagic cell line, J774A.1 in order to better understand the mechanisms underlying OTA immunotoxicity. OTA (30 nM–100 μM) induces a time and concentration dependent cytotoxic effect, increased when cells were co-stimulated with LPS (100 ng/ml), a concentration that alone did not modify the cellular viability. Moreover, OTA (3 μM) alone induces a significant increase in cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, while at the highest concentration (10 μM) a reduced expression of both enzymes was shown, consistently with the mycotoxin cytotoxic profile. The role of nuclear factor-kB (NF-kB) in the mycotoxin effect was also demonstrated. Conversely, when cells were co-stimulated with LPS, OTA showed a concentration-dependent reduction of COX-2 and iNOS expression and their respective metabolites (PGE 2 and NO). These results confirm the pro-inflammatory role of OTA by itself, and demonstrate the impaired capability of OTA-treated macrophages to respond properly to noxious stimuli, such as LPS, mimicking the environmental co-exposure to both compounds.

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.

In 2001, samples of liver (n = 38) and perirenal fat (n = 25) (only in males) were taken from European roe deer (Capreolus capreolus) populating a hilly, wooded protected area in the Emilia-Romagna region of Northern Italy. Samples were analyzed for organochlorine pesticides dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), hexachlorocycloexane alpha-, beta- and gamma-isomers (alpha-, beta- and gamma-HCH), alpha-endosulfan, aldrin, dieldrin and endrin, and the seven PCB 'indicator' congeners IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180, in order to investigate the current state of contamination of the area and to assess the possible toxicological risks for the monitored species. p,p'-DDE was detected in 95% of the liver and perirenal fat samples (n = 63), at concentrations ranging from < dl to 629.3 ng/g lipid weight, which were much higher than those found for HCB and gamma-HCH. The concentrations of the other measured organochlorine pesticides and metabolites were below the detection limit in all the samples. PCBs were found in 97% of the liver and perirenal fat samples, at total levels ranging between < dl to 414.5 ng/g lipid weight. The hepta- and hexa-chlorinated congeners 180, 153 and 138 were predominant and comprised more than 70% of the total seven PCBs in both the liver and perirenal fat samples. In the male roe deer, significantly higher concentrations of HCB, p,p'-DDE and PCBs were found in the liver than in the perirenal fat (P < 0.001). Hepatic levels of p,p'-DDE and PCBs were significantly higher in males than in females (P < 0.05 and P < 0.001, respectively). No significant differences in organochlorine concentrations were observed between juvenile and adult males in either tissue sample (P > 0.05). Females were not statistically tested because they were all adults. The levels of organochlorine contaminants were well below those associated with adverse reproductive effects and lethality in mammals.

Liver samples of 12 species of birds of different trophic levels, collected during the period 1998-2000 from coastal areas of the Campania region, Southern Italy, were analyzed for organochlorine pesticides (OCs), such as dichlorodiphenyltrichloroethane (DDT) and its metabolites, hexachlorobenzene (HCB), gamma-hexachlorocycloexane (gamma-HCH), aldrin, dieldrin, endrin, and the seven PCB "target" congeners, IUPAC Nos. 28, 52, 101, 118, 138, 153 and 180. p,p'-DDE was present in all the samples analyzed, at concentrations ranging from 4 to 4504 ng/g wet wt, which were much higher than those found for HCB, dieldrin, and p,p'-DDD. The concentrations of the others OCs were below the detection limit in all the samples. PCBs were found in all the bird species at levels ranging between 6 and 8431 ng/g wet wt. The hepta-, hexa-, and penta-chlorinated congeners 180, 153, 138, and 118 were predominant since, in almost all the species, they contributed to more than 98% of the total seven determined PCBs. No significant differences in mean concentrations of organochlorine pesticides are detected between single species or between species grouped according to their feeding habits (p > 0.05). However, p,p'-DDE levels were higher in carnivorous species than in omnivorous and insectivorous ones (carnivorous > omnivorous > insectivorous). Concentrations of total PCBs were significantly higher in omnivorous birds than in carnivorous (p < 0.01) and insectivorous ones (p < 0.001), whereas carnivorous birds exhibited significantly higher total PCB levels than insectivorous ones (p < 0.01). Marked differences in total PCB concentrations were found also between single species (from p < 0.05 to p < 0.001). Levels of OCs and PCBs were generally below the thresholds known to affect reproduction, however, mean hepatic concentrations of total PCBs in the yellow-legged herring gull (Larus cachinnans), black-headed gull (Larus ridibundus), and kestrel (Falcus tinnunculus) were far higher than those estimated to elicit immunosuppressive effects and possibly increase susceptibility to parasitoses.

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.

In both man and the dog, anaemia resulting from natural leishmaniasis is often severe and mainly associated with a shortened life span of erythrocytes. Lipid fluidity of erythrocyte membranes from 17 dogs with anaemia caused by visceral leishmaniasis was investigated by means of fluorescence polarization. Results were compared with those from three groups of control animals (10 healthy dogs, seven dogs with visceral leishmaniasis but no anaemia, and 10 dogs with anaemia unrelated to leishmaniasis). Fluorescence polarization values recorded for animals with leishmaniasis-associated anaemia were elevated-indicating reduced erythrocyte membrane fluidity-and significantly higher than in the control groups. Mechanical sequestration by the spleen due to increased cell rigidity, or alterations in receptor/ligand erythrocyte cytoadherence mechanisms, or both, may result fi-om decreased membrane fluidity and hence contribute to the anaemia of Leishmania-infected dogs.