Pleiotropic effects of hexavalent chromium (CrVI) in Mytilus galloprovincialis digestive gland.

Hexavalent Chromium Cr(VI) is an important contaminant considered as a model oxidative toxicant released from both domestic and industrial effluents, and represents the predominant chemical form of the metal in aquatic ecosystems. On the other hand, in mammals the reduced form Cr(III) is considered an essential microelement, involved in regulation of lipid and carbohydrate metabolism; moreover, recent evidence suggests that Cr may have endocrine effects. In this work, the effects of Cr(VI) were investigated in the digestive gland of the marine bivalve Mytilus Keywords: galloprovincialis. Mussels were exposed to 0.1–1–10–100 lg Cr(VI) LÀ1 animalÀ1 for 96 h. At 100 lg LÀ1, a Cr(VI) large increase in total Cr tissue content was observed; in these conditions, the lysosomal membranes Bivalves were completely destabilized, whereas other lysosomal biomarkers (neutral lipids-NL and lipofuscin- Digestive gland LF), as well as different enzyme activities and gene expression were unaffected, this indicating severe Lysosomal biomarkers stress conditions in the tissue. On the other hand, at lower concentrations, changes in other histochem- Glycolytic enzymes ical, biochemical and molecular endpoints were observed. In particular, at both 1 and 10 lg LÀ1, lyso- Gene expression somal destabilization was associated with significant NL and LF accumulation; however, no changes in catalase and GSH transferase (GST) activities were observed. At the same concentrations, GSSG reductase (GSR) activity was significantly increased, this probably reflecting the recycling of GSSG produced in the GSH-mediated intracellular reduction of Cr(VI). Increased activities of the key glycolytic enzymes PFK (phosphofructokinase) and PK (pyruvate kinase) were also observed, indicating that Cr(VI) could affect carbohydrate metabolism. Cr(VI) induced downregulation or no effects on the expression of metallothio- neins MT10 and MT20, except for an increase in MT20 transcription in males. Moreover, significant up- regulation of the Mytilus estrogen receptor MeER2 and serotonin receptor (5-HTR) were observed in both sexes. The results demonstrate that exposure to Cr(VI) in the low ppb range did not result in strong toxicity or oxidative stress conditions in mussel digestive gland. On the other hand, our data support the hypothesis that low concentrations of the metal can exert pleiotropic effects on mussel physiology, from modulation of lipid and carbohydrate metabolism, to effects on the expression of estrogen-responsive genes

The impact of long-term exposure to Space environment on adult mouse testis

The presence of 3- and 17 \u3b2 HSD, the mRNA expression of FSH receptor (FSHR), LH receptor (LHR) and androgen receptor (AR), interleukin-1\u3b2 (IL-1\u3b2) were evaluated, by quantitative RT-PCR, in the testis of mice (C57BL/10) under different gravity conditions (0 g: MDS, 91 days in International Space Station, ISS, and 1 g: ground control) either wild type or pleiotrophin transgenic (overexpressing osteoblast stimulating factor-1). Histological examination of the testes of the control groups revealed regularly configured seminiferous tubules. The testes from spaceflown animals show disorganization, sloughing of cells in the lumen, separation of germ cells from the basal laminae and vacuolation of the germinal epithelium. The interstitial tissue displayed inflammatory exudates. No great differences are observed between Wild (WT) and Transgenic (TG) mice. Immunihistochemistry for 3\u3b2-HSD and 17\u3b2-HSD shows similar localization in Leydig cells in all animals. Therefore the immunoreactions of ISS (WT and TG) decreases. HSP70 immunohistofluorescence was localized in the interstitial tissue in flown samples. Transcription of the studied genes was comparable in the ground controls, with slightly higher levels of mRNA transcripts in Transgenic mice with respect to WT. Microgravity did not affect expression of LHR in both samples, whereas an increase in FSHR was observed in WT. On the other hand, higher levels of mRNA transcripts for AR observed in flown testes (WT and TG). Moreover, a particularly high expression of IL-1\u3b2 was observed in samples from ISS

Effects of sublethal, environmentally relevant concentrations of hexavalent chromium in the gills of Mytilus galloprovincialis

Hexavalent chromium Cr(VI) is an important contaminant released from both domestic and industrial effluents, and represents the predominant chemical form of the metal in aquatic ecosystems. In the marine bivalve Mytilus galloprovincialis exposure to non-toxic, environmentally relevant concentrations of Cr(VI) was shown to modulate functional parameters and gene expression in both the digestive gland and hemocytes. In this work, the effects of exposure to Cr(VI) (0.1–1–10 g L−1 animal−1 for 96 h) in mussel gills were investigated. Gill morphology and immunolocalization of GSH-transferase (GST), of components involved in cholinergic (AChE and ChAT), adrenergic (TH) and serotoninergic (5-HT3 receptor) systems, regulating gill motility, were evaluated. Total glutathione content, activities of GSH-related enzymes (glutathione reductase – GSR, GST), of catalase, and of key glycolytic enzymes (phosphofructokinase – PFK and pyruvate kinase – PK) were determined. Moreover, mRNA expression of selected Mytilus genes (GST-, metallothionein isoforms MT10 and MT20, HSP70 and 5-HT receptor) was assessed by RT-q-PCR. Cr(VI) exposure induced progressive changes in gill morphology and in immunoreactivity to components involved in neurotransmission that were particularly evident at the highest concentration tested, and associated with large metal accumulation. Cr(VI) increased the activities of GST and GSR, and total glutathione content to a different extent at different metal concentrations, this suggesting Cr(VI) detoxication/reduction at the site of metal entry. Cr(VI) exposure also increased the activity of glycolytic enzymes, indicating modulation of carbohydrate metabolism. Significant changes in transcription of different genes were observed. In particular, the mRNA level for the 5-HTR was increased, whereas both decreases and increases were observed for GST-, MT10, MT20 and HSP70 mRNAs, showing sex- and concentration-related differences. The results demonstrate that Cr(VI) significantly affected functional and molecular parameters in mussel gills, and indicate that this tissue represents the major target of exposure to environmentally relevant concentrations of the meta

Direct effects of Bisphenol A on lipid homeostasis in rat hepatoma cells

Bisphenol A (BPA) is one of the most abundant endocrine disruptors in the environment, considered as a weak xenoestrogen. BPA has recently become of additional public health concern because of increasing evidence of deleterious effects on metabolism. Dietary intake seems the most important exposure route for BPA, followed by rapid biotransformation in the gut and liver and elimination in the urine. Although hepatocytes can represent a significant target for the effects of BPA, little is known on the direct effects and mechanisms of action of BPA on lipid homeostasis in these cells. In this work, the effects of BPA (0.3-3-30-300 ng/ml, 24 h) were investigated in rat FaO hepatoma. BPA significantly increased intracellular triglyceride (TAG) content and lipid accumulation in lipid droplets. The effects of BPA were associated with decreased mRNA levels of the transcription factors Peroxisome Proliferator-Activated Receptor isoforms \u3b1 and alpha and beta as well as of their downstream genes acyl-CoA oxidase and carnitine palmitoyl transferase involved in lipid oxidation. BPA also decreased transcription of ApolipoproteinB and the extracellular TAG content. FaO cells did not express Estrogen Receptors (ERalpha and ERbeta). All the effects of BPA were prevented by cell pretreatment with Wortmannin, indicating the involvement of PI-3 kinase. The results demonstrate a direct action of BPA on lipid homeostasis apparently through interference with the pathways involved in lipid oxidation and secretion