BDE-209 exposure in murine melanoma (B16-F1) cells modulates tumor malignancy and progression in vivo.

Melanoma is a type of skin cancer considered aggressive due to its high metastatic ability and rapid progression to other tissues and organs. BDE-209 (2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether) is an additive used as a flame retardant and classified as a persistent organic pollutant that has a high bioaccumulation capacity due to its lipophilic nature. This substance has already been detected in rivers, air, soil, plants and even in different human biological samples, such as plasma, umbilical cord blood and breast milk, revealing a great concern to human populations. Thus, in the current study we investigated whether prior exposure of murine melanoma B16-F1 cells to BDE-209 modulates in vivo progression and malignancy of melanoma. B16-F1 cells were cultured and exposed in vitro to BDE-209 (0.01, 0.1 e 1 nM) for 15 days and then inoculated, via caudal vein, in C57BL/6 mice for experimental metastasis analysis after 20 days. Inoculation of BDE-209-exposed cells resulted in 82% increase of metastasis colonized area in the lungs of mice, downregulation of tumor suppressors genes, such as Timp3 and Reck, decrease of lipid peroxidation and increase of systemic and local inflammatory response. These findings are related to melanoma progression. Additionally, the histopathological analysis revealed greater number of focal points of metastases in the lungs and invasiveness of metastases to the mice brain (89%). The results showed that exposure to BDE-209 may alter the phenotype of B16-F1 cells, worsening their metastatic profile. Current data showed that BDE-209 may interfere with the prognosis of melanoma by modulating cells with less invasiveness capacity to a more aggressive profile.

BDE-99 (2,2',4,4',5 - pentain polybrominated diphenyl ether) induces toxic effects in Oreochromis niloticus after sub-chronic and oral exposure.

PBDEs are toxic, lipophilic, hydrophobic, and persistent artificial chemicals, characterized by high physical and chemical stability. Although PBDEs are known to disturb hormone signaling, many effects of 2,2',4,4',5 - pentain polybrominated diphenyl ethers (BDE-99) in fish remain unclear. The current study investigates the effects of BDE-99 in Oreochromis niloticus where sixty-four juvenile fish were orally exposed to 0.294, 2.94, 29.4 ng g-1 of BDE-99, every 10 days, during 80 days. The results showed histopathological findings in liver and kidney, increasing acetylcholinesterase activity in muscle, disturbs in the antioxidant system in liver and brain and decreasing the plasmatic levels of vitellogenin in females. According to multivariate analysis (IBR), the higher doses are related to the interaction of oxidative and non-oxidative enzymes. The present study provided evidence of deleterious effects after sub-chronic exposure of BDE 99 to O. niloticus, increasing the knowledge about its risk of exposure in fish.

Chemical pollution impairs the health of fish species and fishery activities along the Algeria coastline, Mediterranean Sea.

Chronic exposure to multiple pollutants affects aquatic organisms, even at low concentrations, and can impair fishery activities along marine coastlines. The bioavailability of toxic metals and the presence of metals and polycyclic aromatic hydrocarbons (PAHs) in both water and sediment can explain the worst-case scenario of fish health and fishery production decline along the Algeria coastline. The hepatosomatic index (HIS), gonadosomatic index (GSI), and condition factor (K) in the studied species from the Algiers, Bou Ismail, and Zemmouri bays are the first indicators of the poor environmental health along the studied region. These findings could be explained by the bioavailability of Zn, Cu, Cr, Mn, Hg, and Ni and the detection of PAHs in the water and sediment of these bays. Additionally, histopathological damage in the liver is described in sardine (Sardina pilchardus), anchovy (Engraulis encrasicolus), and sardinelle (Sardinella aurita) highlights the current study in the investigation of the risk of exposure to biota or human populations. The occurrence of permanent lesions in the livers of fish impairs organ function and increases the incidence of diseases affecting the fish community. Furthermore, the factor analysis with principal component analysis (FA/PCA) dataset explains the physiological disturbances described in all studied species. These findings revealed that Zemmouri bay is the most affected by chemicals, suggesting that S. pilchardus is the most sensitive species. Finally, the results showed that the bioavailability of chemicals present in the studied bays confirms poor water quality, which can explain the decrease in fishery production along the Algerian Coastline.

Effects of trophic 2,2', 4,4'-tetrabromodiphenyl ether (BDE-47) exposure in Oreochromis niloticus: A multiple biomarkers analysis.

Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g-1) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.

Oral exposure to BDE-209 modulates metastatic spread of melanoma in C57BL/6 mice inoculated with B16-F10 cells.

Polybrominated diphenyl ethers (PBDEs) are brominated, persistent and bioaccumulative flame retardants widely used in the manufacture of plastic products. Decabromodiphenyl ether (BDE-209) is the most prevalent PBDE in the atmosphere and found in human blood, breast milk and umbilical cord. In vitro studies showed that BDE-209 interferes with murine melanoma cells (B16F10), modulating cell death rates, proliferation and migration, important events for cancer progression. In order to evaluate if BDE-209 modulates metastasis formation in murine models, C57BL/6 mice were exposed to BDE-209 (0.08, 0.8 and 8 µg/kg) via gavage (5-day intervals for 45 days) (9 doses in total). Then, mice were inoculated with melanoma cells (B16-F10) at caudal vein receiving 4 additional doses of BDE-209. At 20th day post-cell inoculation, blood, lung, liver, kidney and brain were sampled for hematological, biochemical and morphological analyses. The slightly higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the blood and pro-oxidant state in the liver of BDE-exposed mice indicated liver damage. Although the in vivo approach is for metastasis formation in the lung, they were unexpectedly observed in non-target organs (liver, brain, kidney and gonads). The similarity test showed high proximity among individuals from the control and a dissimilarity index between the control and exposed groups. The present data corroborate the known hepatotoxicity of BDE-209 to mice (C57BL/6) and demonstrate for the first time the increase of metastatic dissemination of B16F10 cells in vivo due to previous and continuous BDE-209 exposure, revealing possible implications of this organic compound with melanoma malignancy related traits.

Evaluation of Mn exposure in the male reproductive system and its relationship with reproductive dysfunction in mice.

Manganese (Mn) is essential for animal development and homeostasis. However, anthropogenic activities increase the concentration of Mn in the environment and lead to increased risk of exposure to high doses of the metal. Thus, this study aimed to evaluate the effect of high doses of Mn on the male reproductive system of swiss mice. The 22-day old mice were randomly sorted into four groups and exposed to 0 (control), 15, 30 and 60 mg of MnCl2/kg/day, via daily gavages for 45 days. After the exposure, the mice were euthanized and sperm, hormonal and oxidative stress endpoints were evaluated in the testis, seminal vesicle and hypothalamus. Exposure to Mn promoted weight reduction of androgen-dependent organs, as well as alteration of the levels of fecal androgenic metabolites. Sperm parameters were drastically affected in all treated groups and the antioxidants tested (catalase and glutathione-disulfide reductase activities, and non-protein thiols content) decreased in the testis. However, only a few endpoints were altered in the seminal vesicle. For the hypothalamus, there was a reduction in acetylcholinesterase activity, suggesting a neurotoxic potential of Mn. In conclusion, Mn may affect the hypothalamic-gonadal axis by impairing the development of androgen-dependent organs, testicular redox status and Leydig cell maturation.

Multigenerational analysis of the functional status of male reproductive system in mice after exposure to realistic doses of manganese.

The present study aimed to analyze the effect of multigenerational exposure to Mn at realistic doses on the functional quality of the male reproductive system of mice. Females and males (generation F0) were treated for 60 days with MnCl2, via gavage, at the doses of 0, 0.013, 0.13, and 1.3 mg/kg/day. Treatment of F0 dams continued throughout gestation and lactation periods. At the time of weaning, the offspring (F1 generation) was divided into: animals that were not exposed after weaning - parental exposure (PE); and those exposed via parental generation and directly (PDE) for additional 60 days, at the same dose of F0 generation. F0 and F1 males were euthanized for assessment of sperm parameters and redox changes in the reproductive system. There was a decrease in the sperm concentration of the F0 generation. In addition, the sperm parameters of F1 generation were drastically affected. The activity of antioxidant enzymes was significantly reduced in PE animals. It was possible to verify that the biochemical damages were higher in the PE individuals, as demonstrated by the integrated biomarker response index. Our results show that Mn, even at low doses, is able to promote a reduction in sperm quality over a generation.