Do Organochlorine Contaminants Modulate the Parasitic Infection Degree in Mediterranean Trout (Salmo trutta)?

We investigated the occurrence of organochlorine pollutants (OCs) in the muscle of brown trout and evaluated their potential modulation of parasite infection. The toxicological risk for consumer health was assessed, too. Trout were collected from the Sila National Park (Calabria region, South of Italy). The highest concentrations emerged for the sum of the 6 non-dioxin-like (ndl) indicator polychlorinated biphenyls (Σ6ndl-PCBs), followed by the 1,1,1-trichloro-2,2-di(4-chlorophenyl)-ethane (DDT), dioxin-like PCBs, hexachlorobenzene (HCB), and dieldrin. Measured on lipid weight (LW), the mean value of Σ6ndl-PCBs amounted to 201.9 ng g-1, that of ΣDDTs (the sum of DDT-related compounds) to 100.2 ng g-1, with the major contribution of the DDT-metabolite p,p'-DDE which was detected in all sample units (97.6 ng g-1 on average). Among dioxin-like congeners, PCB 118 showed the highest mean concentration (21.96 ng g-1 LW) and was detected in all sample units. Regression analysis of intestinal parasites on OC concentration was performed, controlling for two potential confounding factors, namely sex and sexual stage. The results evidenced the existence of interactions between the dual stressors in the host-parasite system in the wild. A negative and statistically significant correlation was estimated, suggesting that OCs may decrease parasite infection degree. Regarding the toxicological risk evaluation, OC concentrations were consistently below the current European Maximum Residue Limits.

Subchronic Exposure to Polystyrene Microplastic Differently Affects Redox Balance in the Anterior and Posterior Intestine of Sparus aurata.

Microplastics (MPs) are pollutants widely distributed in aquatic ecosystems. MPs are introduced mainly by ingestion acting locally or in organs far from the gastroenteric tract. MPs-induced health consequences for fish species still need to be fully understood. We aimed to investigate the effects of the subchronic oral exposure to polystyrene microplastics (PS-MPs) (1-20 µm) in the gilthead seabreams (Sparus aurata) used as the experimental model. We studied the detrimental impact of PS-MPs (25 and 250 mg/kg b.w./day) on the redox balance and antioxidant status in the intestine using histological analysis and molecular techniques. The research goal was to examine the anterior (AI) and posterior intestine (PI) tracts, characterized by morphological and functional differences. PS-MPs caused an increase of reactive oxygen species and nitrosylated proteins in both tracts, as well as augmented malondialdehyde production in the PI. PS-MPs also differently affected gene expression of antioxidant enzymes (i.e., superoxide dismutase, catalase, glutathione reductase). Moreover, an increased up-regulation of protective heat shock proteins (HSPs) (i.e., hsp70 and hsp90) was observed in PI. Our findings demonstrate that PS-MPs are responsible for oxidative/nitrosative stress and alterations of detoxifying defense system responses with differences in AI and PI of gilthead seabreams.

The Pressing Issue of Micro- and Nanoplastic Contamination: Profiling the Reproductive Alterations Mediated by Oxidative Stress.

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.

Palmitoylethanolamide Promotes White-to-Beige Conversion and Metabolic Reprogramming of Adipocytes: Contribution of PPAR-α.

The potential role of brown and beige adipose tissue against obesity has been recognized. Browning, or beiging of white adipose tissue (WAT) is associated with the remodeling of adipocytes and the improvement of their metabolic and secretory functions. Here, palmitoylethanolamide (PEA) restore the plasticity of brown and white adipocytes impaired in mice on a high-fat diet (HFD). Young male C57Bl/6J mice were fed with control (STD) diet or HFD for 12 weeks. Ultramicronized PEA (30 mg/kg/die p.o.) was administered for an additional 7 weeks, together with HFD. PEA recovered interscapular brown fat morphology and function, increasing UCP1 positivity, noradrenergic innervation, and inducing the mRNA transcription of several specialized thermogenic genes. PEA promotes the beige-conversion of the subcutaneous WAT, increasing thermogenic markers and restoring leptin signaling and tissue hormone sensitivity. The pivotal role of lipid-sensing peroxisome proliferator-activated receptor (PPAR)-α in PEA effects was determined in mature 3T3-L1. Moreover, PEA improved mitochondrial bioenergetics in mature adipocytes measured by a Seahorse analyzer and induced metabolic machinery via AMPK phosphorylation. All these outcomes were dampened by the receptor antagonist GW6471. Finally, PEA induced adipogenic differentiation and increased AMPK phosphorylation in human adipose-derived stromal cells (ASCs) obtained from subcutaneous WAT of normal-weight patients and patients with obesity. We identify PEA and PPAR-α activation as the main mechanism by which PEA can rewire energy-storing white into energy-consuming brown-like adipocytes via multiple and converging effects that restore WAT homeostasis and metabolic flexibility.

Oral Bisphenol A Worsens Liver Immune-Metabolic and Mitochondrial Dysfunction Induced by High-Fat Diet in Adult Mice: Cross-Talk between Oxidative Stress and Inflammasome Pathway.

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'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 µg/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.

Oxidative Stress and BPA Toxicity: An Antioxidant Approach for Male and Female Reproductive Dysfunction.

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.

PCB levels in adipose tissue of dogs from illegal dumping sites in Campania region (Italy).

The aim of the study is to investigate the potential relationship between exposure to PCBs and cancer. In doing so we relied on a sample of dogs coming from a peculiar area of the Campania region (Italy), that has been suffering for illegal waste dumping and open air burning of plastic waste for many years. The latter determined the release of organic and inorganic pollutants, such as the PCBs. By comparing dogs with cancer and healthy dogs, we found much higher PCB concentrations in the former, with a significant difference (p < 0.05) for the non-indicator ∑10NDL-PCB and the DL-PCBs. A regression analysis, controlling for three potentially confounding factors, that are sex, age and weight, confirmed the higher ∑10NDL-PCB concentration in dogs with cancer. Hence, our evidence suggests a potential health hazard for animals and likewise people living in a risky area due to the presence of environmental organic pollutants.

Polychlorinated Biphenyls (PCB 101, 153, and 180) Impair Murine Macrophage Responsiveness to Lipopolysaccharide: Involvement of NF-κB Pathway.

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.

Polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) alter leptin signaling and lipid metabolism in differentiated 3T3-L1 adipocytes.

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.