Toxicity of perfluoroalkyl substances (PFAS) toward embryonic stages of mahi-mahi (Coryphaena hippurus).

Perfluoroalkyl substances (PFAS) are highly persistent organic pollutants that have been detected in a wide array of environmental matrices and, in turn, diverse biota including humans and wildlife wherein they have been associated with a multitude of toxic, and otherwise adverse effects, including ecosystem impacts. In the present study, we developed a toxicity assay for embryonic stages of mahi-mahi (Coryphaena hippurus), as an environmentally relevant pelagic fish species, and applied this assay to the evaluation of the toxicity of "legacy" and "next-generation" PFAS including, respectively, perfluorooctanoic acid (PFOA) and several perfluoroethercarboxylic acids (PFECA). Acute embryotoxicity, in the form of lethality, was measured for all five PFAS toward mahi-mahi embryos with median lethal concentrations (LC50) in the micromolar range. Consistent with studies in other similar model systems, and specifically the zebrafish, embryotoxicity in mahi-mahi generally (1) correlated with fluoroalkyl/fluoroether chain length and hydrophobicity, i.e., log P, of PFAS, and thus, aligned with a role of uptake in the relative toxicity; and (2) increased with continuous exposure, suggesting a possible role of development stage specifically including a contribution of hatching (and loss of protective chorion) and/or differentiation of target systems (e.g., liver). Compared to prior studies in the zebrafish embryo model, mahi-mahi was significantly more sensitive to PFAS which may be related to differences in either exposure conditions (e.g., salinity) and uptake, or possibly differential susceptibility of relevant targets, for the two species. Moreover, when considered in the context of the previously reported concentration of PFAS within upper sea surface layers, and co-localization of buoyant eggs (i.e., embryos) and other early development stages (i.e., larvae, juveniles) of pelagic fish species to the sea surface, the observed toxicity potentially aligns with environmentally relevant concentrations in these marine systems. Thus, impacts on ecosystems including, in particular, population recruitment are a possibility. The present study is the first to demonstrate embryotoxicity of PFAS in a pelagic marine fish species, and suggests that mahi-mahi represents a potentially informative, and moreover, environmentally relevant, ecotoxicological model for PFAS in marine systems.

Interaction of selenium with copper, silver, and gold salts. Electron microprobe study.

The interaction of selenium with elements of group 1b of the periodic system, i.e. copper, silver, and gold was studied. Electron probe microanalysis was used to detect elements in intracellular organelles. Administration of copper, silver, or gold salts (the latter being used in chrysotherapy) showed that these elements were concentrated in the lysosomes of the liver or kidney in the presence of sulfur. Silver salts were also precipitated in glomerular basement membranes. The action of selenium enhances this intralysosomal process of concentration and precipitation. Sulfur and selenium are detected in the lysosome and this makes identification of the precipitate difficult. The action of selenium, which consists in removing toxic elements from the systemic circulation and concentrating them in the lysosomes, is in most cases beneficial for the organism. This mechanism, which has already been studied for arsenic, is extended in this study to other elements.

Selenium-arsenic interaction in renal cells: role of lysosomes. Electron microprobe study.

Selenium can modify the toxicity of different elements. Selenium and the element form a complex that is precipitated in the tissues and inhibits the toxicity of the element. We studied the interaction of arsenic and selenium at the subcellular level in rat kidney cells using electronic probe microanalysis that permits detection of elements in the intracellular organelles. This showed that arsenic and selenium are concentrated and precipitated in the lysosomes of the renal cells in the form of insoluble selenide (As2Se). In the long term, the lysosomes and their precipitate are eliminated in the urine. These processes enable the lethal toxicity of arsenic to be inhibited. This intralysosomal concentration and precipitation can serve as a model for the mechanism of interaction of selenium with other elements and can be compared with other mechanisms of concentration and precipitation of elements in the lysosomes.

Cis DDP in combination with selenium and sulfur. Subcellular effect in kidney cells. Electron microprobe study.

Cis DDP is an anticancer agent used in the treatment of diverse cancers, but its use has been limited by its nephrotoxic effect. We sought to modify this major toxic side effect by the addition of S2O3-- (sodium thiosulfate) or SeO2 (selenium dioxide) or both. In the present study, only ultrastructural and X-ray microanalysis data are reported. No kidney lesions were observed after the administration of SeO2 and Cis DDP in contrast to Cis DDP with S2O3-- or with S2O3-- plus selenium. An organelle of the kidney cell, the lysosome, has a particular role in the concentration of mineral elements in this cell. Platinum was observed in the lysosome along with sulfur, after the administration of Cis DDP and S2O3. Platinum, selenium and sulfur were observed after administration of SeO2, S2O3 and Cis DDP. No mineral deposits were observed after administration of SeO2 and Cis DDP. The role of sulfur seems to be very different from that of selenium. We hypothesize that sulfur favors the intralysosomal concentration of platinum or that selenium associates with platinum. The fact that selenium is not reabsorbed by the kidney cell seems to favor the hypothesis of urinary elimination of platinum. The present work confirms our previous study concerning the role of SeO2 in combination with Cis DDP.

Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma.

cis-Diamminedichloroplatinum(II) (cis-DDP) is a well-known anticancer agent the use of which is limited by its toxicity. Since it has been demonstrated that selenium is able to combine with metals like cadmium and mercury and to reduce their toxicity, we decided to investigate whether it could reduce the toxicity of platinum. We treated fibrosarcoma-bearing mice with a combination of cis-DDP and selenium. The dose of 2 or 4 micrograms selenium/g animal weight had no effect on tumor growth. The i.p. injection of 16 micrograms cis-DDP/g led to early death of animals. The i.p. treatment of tumor-bearing animals with 2 or 4 micrograms of selenium reduced the early mortality induced by cis-DDP at a dose of 16 micrograms/g. Therefore, the addition of selenium allowed the administration of high doses of cis-DDP, which resulted in an improved antitumor effect. Clonogenic assays following drug exposure showed that selenium had no direct effect on tumor cells and did not modify the antitumor activity of cis-DDP. Electron microscopy showed reduced changes in renal cells when selenium was added to the cis-DDP treatment. Microanalysis showed no accumulation of either selenium or platinum within renal cells. These results suggest that the addition of selenium decreases the nephrotoxicity of cis-DDP.

Selenium and kidney deposits in experimental argyria. Electron microscopy and microanalysis.

The conjugate effects of selenium and silver salts were studied in experimental renal argyria. Microanalysis has led to the localization of products of chemical reactions to Se and Ag in tissue sections. After prolonged treatment with Ag salts alone, there was Ag and S deposits in basal membranes. When Se and Ag were used together, the formation of these deposits in glomerular basal membranes was accelerated spectacularly. Electron probe microanalysis has shown that Se replaces S in silver deposits. Compared to its effect on other metals, Se was shown to have a complex action, characterized primarily by its toxic effect, favoring the appearance of symptoms of argyria.