The increasing release of chiral chemicals into the environment dictates attention to a better understanding of enantioselectivity in their human and ecotoxicological effects. Although enantioselectivity has been considered in many recent studies, there is little effort for discerning the connection between different processes, and as such, our current knowledge about chiral contaminants is rather scattered and incoherent. In this study, we simultaneously evaluated enantioselectivity of two chiral pesticides, lambda-cyhalothrin (LCT) and (Z)-cis-bifenthrin (cis-BF), in immunotoxicity to macrophage cells (RAW264.7), and endocrine disruption activity in human breast carcinoma cell line MCF-7. Analysis of cell proliferation, cell viability, apoptosis, and receptor gene expression showed significant differences between the enantiomers of LCT or cis-BF in estrogenic potential and immunocytotoxicity. The selectivity in these effects consistently followed the same direction, with (−)-LCT or 1S-cis-BF displaying a greater activity than its counterpart. The consistency was attributed to interplaying mechanisms in the closely interacting immune and endocrine systems. The underlying interplays suggest that other chiral xenobiotics may also show a directional enantioselectivity in immunotoxicity and endocrine toxicity. Given that many biological processes are inter-related, enantioselectivity may follow specific patterns that can be revealed via integrative assessments as demonstrated in this study.

Quantum dots (QDs) are nanoparticles of inorganic semiconductors and have great promise in various applications. Many studies have indicated that mitochondria are the main organelles for the distribution and toxic effects of QDs. However, the underlying mechanism of QDs interacting with mitochondria and affecting their function is unknown. Here, we report the mechanism of toxic effects of 3-mercaptopropionic acid (MPA)-capped CdTe QDs on mitochondria. Human liver carcinoma (HepG2) cells were exposed to 25, 50 and 100 μmol/L of MPA-capped CdTe QDs. The results indicated that MPA-capped CdTe QDs inhibited HepG2 cell proliferation and increased the extracellular release of LDH in a concentration-dependent manner. Furthermore, MPA-capped CdTe QDs caused reactive oxygen species (ROS) generation and cell damage through intrinsic apoptotic pathway. MPA-capped CdTe QDs can also lead to the destruction of mitochondrial cristae, elevation of intracellular Ca²⁺ levels, decreased mitochondrial transmembrane potential and ATP production. Finally, we showed that MPA-capped CdTe QDs inhibited mitochondrial fission, mitochondrial inner membrane fusion and mitophagy. Taken together, MPA-capped CdTe QDs induced significant mitochondrial dysfunction, which may be caused by imbalanced mitochondrial fission/fusion and mitophagy inhibition. These findings provide insights into the regulatory mechanisms involved in MPA-capped CdTe QDs-induced mitochondrial dysfunction.

We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 μM Cr and 0.06 μM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been linked to the development of certain diseases. However, the relationship between PAH exposure and thyroid disorders remains unknown. We measured 10 of the most common hydroxylated PAHs (OH-PAHs) in the urine of thyroid nodular goiter (NG) patients, papillary thyroid carcinoma (PTC) patients, and healthy controls by gas chromatography-triple-quadrupole mass spectrometry (GC-MS/MS). We found that the concentrations of 2-hydroxyfluorene (2-OH-FLU), 2-hydroxydibenzofuran (2-OH-DBF), and 1-hydroxyphenanthrene (1-OH-PHE) in the NG group, and of 2-hydroxynaphthalene (2-OH-NAP), 2-OH-DBF, and 1-OH-PHE in the PTC group were significantly higher than those in controls. In addition, participants in the high tertiles of 2-OH-FLU and 1-OH-PHE had higher risk of NG. Besides these two OH-PAHs, elevated risk of NG was observed in women in the high tertiles of 1-hydroxynaphthalene (1-OH-NAP), 2-OH-NAP, 2-OH-DBF, and 3-hydroxyfluorene (3-OH-FLU). Furthermore, participants in the high tertiles of seven OH-PAHs, namely, 1-OH-NAP, 2-OH-NAP, 2-OH-DBF, 2-OH-FLU, 3-OH-FLU, 3/9-hydroxyphenanthrene (3/9-OH-PHE), and 1-OH-PHE, had elevated risk of PTC, and females in these high tertiles had an even higher risk of PTC. Our findings suggest that PAH exposure may increase the risk of NG/PTC, and there may be a gender-specific effect of PAH exposure on the development of NG/PTC.

While humans are exposed to mixtures of persistent organic pollutants (POPs), their risk assessment is usually based on a chemical-by-chemical approach. To assess the health effects associated with mixed exposures, knowledge on mixture toxicity is required. Several POPs are potential ligands of the Aryl hydrocarbon receptor (AhR), which involves in xenobiotic metabolism and controls many biological pathways. This study assesses AhR agonistic and antagonistic activities of 29 POPs individually and in mixtures by using Chemical-Activated LUciferase gene eXpression bioassays with 3 transgenic cell lines (rat hepatoma DR-H4IIE, human hepatoma DR-Hep G2 and human mammary gland carcinoma DR-T47-D). Among the 29 POPs, which were selected based on their abundance in Scandinavian human blood, only 4 exerted AhR agonistic activities, while 16 were AhR antagonists in DR-H4IIE, 5 in DR-Hep G2 and 7 in DR-T47-D when tested individually. The total POP mixture revealed to be AhR antagonistic. It antagonized EC₅₀ TCDD inducing AhR transactivation at a concentration of 125 and 250 and 500 fold blood levels in DR-H4IIE, DR-T47-D and DR-Hep G2, respectively, although each compound was present at these concentrations lower than their LOEC values. Such values could occur in real-life in food contamination incidents or in exposed populations. In DR-H4IIE, the antagonism of the total POP mixture was due to chlorinated compounds and, in particular, to PCB-118 and PCB-138 which caused 90% of the antagonistic activity in the POP mixture. The 16 active AhR antagonists acted additively. Their mixed effect was predicted successfully by concentration addition or generalized concentration addition models, rather than independent action, with only two-fold IC₅₀ underestimation. We also attained good predictions for the full dose-response curve of the antagonistic activity of the total POP mixture.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that can be present at high levels as mixtures in polluted aquatic environments. Many PAHs are potent mutagens and several are well-known carcinogens. Despite numerous studies on individual compounds, little is known about the toxicity of PAHs mixtures that are encountered in environmental situations. In the presentwork, zebrafish were continuously fed from 5 days post-fertilisation to 14 months post-fertilisation (mpf) with a diet spiked with fractions of either pyrolytic (PY), petrogenic light oil (LO), or petrogenic heavy oil (HO) origin at three concentrations. A decrease in survival was identified after 3 mpf in fish fed with the highest concentration of HO or LO, but not for PY. All PAH fractions caused preneoplastic and neoplastic disorders in longterm-exposed animals. Target tissues were almost exclusively of epithelial origin, with the bile duct epithelium being themost susceptible to chronic exposure to all PAH fractions, and with germ cells being the second most responsive cells. Significantly higher incidences of neoplasms were observed with increasing PAH concentration and exposure duration. Themost severe carcinogenic effects were induced by dietary exposure to HO compared to exposure to LO or PY (45, 30 and 7 %, respectively, after 9 to 10 months of exposure to an intermediate concentration of PAHs). In contrast, earliest carcinogenic effects were detected as soon as 3 mpf after exposure to LO, including the lowest concentration, or to PY. PAHbioactivation and genotoxicity in blood was assessed by ethoxyresorufin-Odeethylase activity quantification and comet and micronuclei assays, respectively, but none of these were positive. Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenotoxic events that impair survival and physiology of exposed fish.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that can be present at high levels as mixtures in polluted aquatic environments. Many PAHs are potent mutagens and several are well-known carcinogens. Despite numerous studies on individual compounds, little is known about the toxicity of PAHs mixtures that are encountered in environmental situations. In the present work, zebrafish were continuously fed from 5 days post-fertilisation to 14 months post-fertilisation (mpf) with a diet spiked with fractions of either pyrolytic (PY), petrogenic light oil (LO), or petrogenic heavy oil (HO) origin at three concentrations. A decrease in survival was identified after 3 mpf in fish fed with the highest concentration of HO or LO, but not for PY. All PAH fractions caused preneoplastic and neoplastic disorders in long-term-exposed animals. Target tissues were almost exclusively of epithelial origin, with the bile duct epithelium being the most susceptible to chronic exposure to all PAH fractions, and with germ cells being the second most responsive cells. Significantly higher incidences of neoplasms were observed with increasing PAH concentration and exposure duration. The most severe carcinogenic effects were induced by dietary exposure to HO compared to exposure to LO or PY (45, 30 and 7 %, respectively, after 9 to 10 months of exposure to an intermediate concentration of PAHs). In contrast, earliest carcinogenic effects were detected as soon as 3 mpf after exposure to LO, including the lowest concentration, or to PY. PAH bioactivation and genotoxicity in blood was assessed by ethoxyresorufin-O-deethylase activity quantification and comet and micronuclei assays, respectively, but none of these were positive. Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenotoxic events that impair survival and physiology of exposed fish.

Reductions of zooplankton biomasses and grazing pressures were observed during overfishing-induced trophic cascades and concurrent oil spills at global scales. Recent phytoplankton increments followed, once Fe-, P-, and N-nutrient limitations of commensal diazotrophs and dinoflagellates were also eliminated by respective human desertification, deforestation, and eutrophication during climate changes. Si-limitation of diatoms instead ensued during these last anthropogenic perturbations of agricultural effluents and sewage loadings. Consequently, ~15% of total world-wide annual asthma trigger responses, i.e. amounting to ~45 million adjacent humans during 2004, resulted from brevetoxin and palytoxin poisons in aerosol forms of western boundary current origins. They were denoted by greater global harmful algal bloom [HAB] abundances and breathing attacks among sea-side children during prior decadal surveys of asthma prevalence, compiled here in ten paired shelf ecosystems of western and eutrophied boundary currents. Since 1965, such inferred onshore fluxes of aerosolized DOC poisons of HABs may have served as additional wind-borne organic carriers of toxic marine MeHg, phthalate, and DDT/DDE vectors, traced by radio-iodine isotopes to potentially elicit carcinomas. During these exchanges, as much as 40% of mercury poisonings may instead have been effected by inhalation of collateral HAB-carried marine neurotoxic aerosols of MeHg, not just from eating marine fish. Health impacts in some areas were additional asthma and pneumonia episodes, as well as endocrine disruptions among the same adjacent humans, with known large local rates of thyroid cancers, physician-diagnosed pulmonary problems, and ubiquitous high indices of mercury in hair, pesticides in breast milk, and phthalates in urine.

The antagonistic side effects of chemical medications led to the search for safe strategies such as biogenic agents. Correspondingly, this study aims to create biogenic, appropriate, auspicious and innovative therapeutic agents like Galaxaura elongata {GE}, Turbinaria ornata {TO} and Enteromorpha flexuosa {EF} macroalgae-based silver nanoparticles (Ag-NPs). The Ag⁺ reduction and the creation of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs have been validated using UV–visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and zeta potential analysis, and the chemical composition of macroalgae crude extracts was estimated through gas chromatography–mass spectrometry (GC–MS). Further, macroalgae-based Ag-NPs were tested for their free radical scavenging activity DPPH, ABTS, anticancer activity in human liver carcinoma (HepG2) cell line, distinctive inflammation forms and elevated α-amylase. Results showed that the biosynthesized Ag-NPs have unique mechanical and physicochemical characters attributed to their high relative surface area, nanosized dimensions and spherical shape. At dose of 200 µg/mL, the DPPH radical scavenging capacity was maximized with Ag[TO]-NPs (67.26%); however, Ag[EF]-NPs was the most potent as ABTs scavenger (97.74%). Additionally, Ag[GE]-NPs had the maximum proteinase inhibitory action with 59.78%. The 1000 µg/mL of Ag[GE]-NPs, Ag[TO]-NPs and Ag[EF]-NPs revealed significant inhibitions of cell growth of HepG2 resulting in cell viabilities 5.92%, 4.44% and 11.33%, respectively. These findings suggest that macroalgae bio-capped Ag-NPs have magnificent biological potentials for safe biomedical applications.

Hepatocellular carcinoma (HCC) is one of the ten most commonly diagnosed cancers. Doxorubicin is an antibiotic used in cancer treatment protocols that has several side effects. L-Arginine is a non-essential amino acid that is used as immune system activation and antitumor drugs. Therefore, the current study was designed to compare using doxorubicin, L-arginine, or their combination as a prophylactic agent against hepatic carcinoma induced by hepatocellular carcinoma cells (HepG2) injection in mice. The mice were divided into five groups: normal mice and mice that received HepG2, doxorubicin and HepG2, L-arginine and HepG2, and doxorubicin, L-Arginine, and HepG2, respectively. Liver function test as, aspartate transaminase (AST) and alanine transaminase (ALT), and alpha-fetoprotein (AFP), caspase 3, interleukin 6 (IL-6), tumor necrotic factor (TNF), lipid peroxidation (NDA), and some antioxidant parameters were determined. A significant increase in AST and ALT, α-fetoprotein, TNF-α, and cytokines IL6 and MDA and a significant decrease in the serum caspase and liver catalase were determined in HepG2-injected mice. Moreover, some large hyperchromatic heptocytes were observed and the percentage of the positive area/field of HepPar-1, the most specific HCC marker, was 9.56%. Interestingly, mice that received doxorubicin, L-arginine, or their combination showed an improvement in some of the previous parameters. The improvement was more prominent with L-arginine administration.