Hepatic metabolism catalyzed by the cytochrome P450 (CYP) superfamily affects liver toxicity associated with exposures to natural compounds and xenobiotic agents. Previously we generated a battery of HepG2-derived stable cell lines that individually express 14 CYPs (1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, 3A4, 3A5, and 3A7). In this study, we comprehensively characterized each cell line for its CYP expression and enzyme activity. Specifically, we measured the mRNA expression, protein expression, and metabolite formation. Using CYP3A4, 2D6, and 2C9-overexpressing cells as representatives, we examined the stability of these cells in long-term cultures for up to 10 passages. The results showed that CYPs can be stably overexpressed for up to 10 cell culture passages without losing their activities. The robustness of responses to stimuli among the cells at different passages was also investigated in CYP3A4-overexpressing cells and the response to amiodarone and dronedarone showed no difference between the cells at the passage 2 and 10. Moreover, the mRNA expression level of most CYPs was higher in CYP-overexpressing HepG2 cells than that in HepaRG cells and primary human hepatocytes. This study confirmed the stability of CYP-overexpressing HepG2 cell lines and provided useful information for a broader use of these cells in pharmacologic and toxicologic research.
Disruption of element homeostasis may contribute to increased susceptibility of men to cancer development. Whether environmental low-level metal exposure could contribute to the pathogenesis of testicular cancer is unknown. Comparison of the level of 18 elements in whole blood, serum and urine and parameters of oxidative stress/antioxidant status between men with testicular germ cell tumors (TGCT) and healthy men showed significant difference between the groups in most parameters. The results of linear discriminant analysis with a discrimination rate of 96% indicated whole blood Ca, Co, Cu, Fe, K, Mg, Na and Zn, serum Ca, Cu, Na and Ni, and urine Cd, Co, Fe and Mn being the strongest predictors of illness. TGCT patients had a significant increase in serum and blood Cu and decrease in serum Fe and blood Zn with cancer progression. Significantly higher concentrations of Al, As, Pb, and Ni in whole blood/serum of men with TGCT confirm the hypothesis that low-level environmental exposure to these elements may contribute to cancer development. Relationship between elements concentrations and treatment outcomes should be carefully monitored during cancer treatment since high concentrations of commonly used platinum-based chemotherapeutics may additionally disturb the homeostasis of elements.
Many metal nanoparticles are reported to have intrinsic enzyme-like activities and offer great potential in chemical and biomedical applications. In this study, PtCu alloy nanoparticles (NPs), synthesized through hydrothermal treatment of Cu2+ and Pt2+ in an aqueous solution, were evaluated for ferroxidase-like and antibacterial activity. Electron spin resonance (ESR) spectroscopy and colorimetric methods were used to demonstrate that PtCu NPs exhibited strong ferroxidase-like activity in a weakly acidic environment and that this activity was not affected by the presence of most other ions, except silver. Based on the color reaction of salicylic acid in the presence of Fe3+, we tested the ferroxidase-like activity of PtCu NPs to specifically detect Fe2+ in a solution of an oral iron supplement and compared these results with data acquired from atomic absorption spectroscopy and the phenanthroline colorimetric method. The results showed that the newly developed PtCu NPs detection method was equivalent to or better than the other two methods used for Fe2+ detection. The antibacterial experiments showed that PtCu NPs have strong antibacterial activity against Staphylococcus aureus and Escherichia coli. Herein, we demonstrate that the peroxidase-like activity of PtCu NPs can catalyze H2O2 and generate hydroxyl radicals, which may elucidate the antibacterial activity of the PtCu NPs against S. aureus and E. coli. These results showed that PtCu NPs exhibited both ferroxidase- and peroxidase-like activity and that they may serve as convenient and efficient NPs for the detection of Fe2+ and for antibacterial applications.
Combinations of semiconductor nanoparticles (NPs) with noble metal NPs enable an increase in the photoactivity of semiconductor NPs into the visible and near-infrared regions. The design rationale of the semiconductor-metal hybrid nanostructures for the optimization of charge carrier separation and reactive oxygen species (ROS) generation remains unclear. In this study, the interactions of Au nanorods (AuNRs) with TiO2 NPs were modulated by controlling their surface charges. Positively charged AuNRs formed aggregates with the negatively charged TiO2 NPs (AuNR@CTAB/TiO2) upon mixing, suggesting that Schottky junctions may exist between Au and TiO2. In contrast, negatively charged AuNRs (AuNR@PSS) remained spatially separated from the TiO2 NPs in the mixed suspension (AuNR@PSS/TiO2), owing to electrostatic repulsion. We used electron spin resonance (ESR) spectroscopy to detect the separation of charged carriers and ROS generation in these two mixtures under simulated sunlight irradiation. We also explored the role of dissolved oxygen in charge carrier separation and ROS generation by continuously introducing oxygen into the AuNR@CTAB/TiO2 suspension under simulated sunlight irradiation. Moreover, the generation of ROS by the AuNR@CTAB/TiO2 and AuNR@PSS/TiO2 mixtures were also examined under 808nm laser irradiation. Our results show that the photogenerated electrons of excited semiconductor NPs are readily transferred to noble metal NPs simply by collisions, but the transfer of photogenerated hot electrons from excited AuNRs to TiO2 NPs is more stringent and requires the formation of Schottky junctions. In addition, the introduction of oxygen is an efficient way to enhance the photocatalytic activity of semiconductor NPs/noble metal NPs system combinations.
The modification of semiconductor nanostructures with metallic nanocomponents can promote the separation of electron/hole from photoexited semiconductors by forming heterojunctions, thus exhibit enhanced photocatalytic activities and potential applications. In this study, Pt-based NPs, including Pt, PtCu, and PtCuCo are employed as model co-catalysts to comparatively study their capability to enhance the photocatalytic activity of TiO2 nanosheets. It was found that each of Pt, PtCu, and PtCuCo can greatly enhance the photocatalytic activity of TiO2 toward degradation of organic dyes. Using electron spin resonance spectroscopy, we demonstrated that deposition of Pt-based NPs resulted in more production of reactive oxygen species including hydroxyl radicals, superoxide, and singlet oxygen. The enhancing effects of Pt-based NPs on generation of ROS and photocatalytic activity showed same trend: PtCuCo > PtCu > Pt. The mechanism underlying the enhancement differences in Pt-based NPs may be mainly related to electronic structure change of Pt in alloying with Cu and Co. These results are valuable for designing hybrid nanomaterials with high photocatalytic efficiency for applications in water purification and antibacterial products.
Aflatoxins [AFs] are secondary metabolites of the fungus species Aspergillus spp. Both animal and epidemiological studies provided sufficient evidence on the carcinogenic, immunotoxic, mutagenic, and genotoxic potential of AFs. While ingestion is the main route of exposure for AFs through consumption of contaminated food products, agricultural workers and personnel who handle AF-contaminated grains are also at higher risk of exposure via inhalation. The main objective of the review is to provide a comprehensive overview of past scientific studies on occupational exposure to AFs, high-risk occupations, and disease outcomes. A search of peer-reviewed articles was done on PubMed and Web of Science Databases. A total of 164 papers was identified and 61 journal articles were selected for further review. High risk occupations include animal husbandry and processing of grain cereals and/or animal feed. Primary liver cancer and respiratory cancers were the most reported as a result of occupational exposure to AFs. For future studies, improved study designs, better characterization of AFs exposure in an occupational setting, and use of biomarkers are recommended in order to promote better understanding of occupational exposure to AFs and the resulting disease burden among workers.
Freshwater harmful algal blooms (HABs) have become a global concern because blooms contain cyanotoxins that can cause liver damage and other negative health impacts. In South Korea, HABs have been frequently observed along the major rivers (Han, Geum, Nakdong, and Youngsan) in recent years. However, there are hardly any studies that report a linkage between HABs and human health, especially along the four major rivers where dams, weirs, and reservoirs were constructed, and sediments were dredged under the Four Major Rivers Project (FMRP) that ended in 2012. The goals of this study were to summarize spatial distribution patterns of HABs and investigate a potential association between HABs and liver diseases. Chlorophyll-a concentration was used to estimate bloom intensity since it was the only available bloom-related parameter that covers the entire rivers. Liver disease data (ICD-10 codes: K71-K77) were sorted by administrative districts. Generalized linear mixed model was used to analyze the bloom, liver diseases, and population data (2005-2016). The results show that chlorophyll-a levels significantly increased since 2013, except Han River region. There was a significant association between HAB intensity and incidence rate of liver diseases, except Han River area, and the extent of association significantly increased after the completion of the FMRP. For future studies, more in-depth epidemiological investigations are warranted in those areas to accurately determine more specific associations between HABs and liver diseases as well as other bloom-related diseases and symptoms. In addition, identification of major exposure pathways to cyanotoxins is needed to better protect public health in those bloom-affected areas.
Nanoscale photocatalysts have attracted abundant research attention in the solar-activated disinfection. In this work, we find that solar irradiation significantly improves the antimicrobial activity of graphene quantum dots (GQDs), accompanied by severe oxidative stress and membrane damage. By using electron spin resonance (ESR) technique, we confirm that different reactive oxygen species (ROS), including singlet oxygen (1O2), hydroxyl radical (•OH), and superoxide anion (O2•-) were generated by GQDs upon irradiation with simulated sunlight. Additionally, these generated ROS will further facilitate lipid peroxidation of cell membrane and suppress bacterial antioxidant systems, enhancing the phototoxicity of GQDs. These findings will bring major advancements of GQDs in applications of solar-driven bacterial disinfection.
Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100 nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H2O2. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.
Silver nanoparticles (AgNP) exhibit size and concentration dependent toxicity to terrestrial plants, especially crops. AgNP exposure could decrease seed germination, inhibit seedling growth, affect mass and length of roots and shoots. The phytotoxic pathway has been partly understood. Silver (as element, ion or AgNP) accumulates in roots/leaves and triggers the defense mechanism at cellular and tissue levels, which alters metabolism, antioxidant activities and related proteomic expression. Botanical changes (either increase or decrease) in response to AgNP exposure include reactive oxygen species generation, superoxide dismutase activities, H2O2 level, total chlorophyll, proline, carotenoid, ascorbate and glutathione contents, etc. Such processes lead to abnormal morphological changes, suppression of photosynthesis and/or transpiration, and other symptoms. Although neutral or beneficial effects are also reported depending on plant species, adverse effects dominate in majority of the studies. More in depth research is needed to confidently draw any conclusions and to guide legislation and regulations.
A comprehensive review of available bioremediation technologies for the pesticide malathion is presented. This review article describes the usage and consequences of malathion in the environment, along with a critical discussion on modes of metabolism of malathion as a sole source of carbon, phosphorus, and sulfur for bacteria, and fungi along with the biochemical and molecular aspects involved in its biodegradation. Additionally, the recent approaches of genetic engineering are discussed for the manipulation of important enzymes and microorganisms for enhanced malathion degradation along with the challenges that lie ahead.
Lead (Pb) exposure during different stages of development has demonstrated dose, duration, sex, and tissue-specific pathophysiological outcomes due to altered epigenetic regulation via (a) DNA methylation, (b) histone modifications, (c) miRNAs, and (d) chromatin accessibility. Pb-induced alteration of epigenetic regulation causes neurotoxic and extra-neurotoxic pathophysiological outcomes. Neurotoxic effects of Pb include dysfunction of memory and learning, behavioral disorder, attention deficit hyperactivity disorder, autism spectrum disorder, aging, Alzheimer's disease, tauopathy, and neurodegeneration. Extra-neurotoxic effects of Pb include altered body weight, metabolic disorder, cardiovascular disorders, hematopoietic disorder, and reproductive impairment. Pb exposure either early in life or at any stage of development results in undesirable pathophysiological outcomes that tends to sustain and maintain for a lifetime.
Environmental exposures to hazardous chemicals are associated with a variety of human diseases and disorders, including cancers. Phase I metabolic activation and detoxification reactions catalyzed by cytochrome P450 enzymes (CYPs) affect the toxicities of many xenobiotic compounds. Proper regulation of CYP expression influences their biological effects. Noncoding RNAs (ncRNAs) are involved in regulating CYP expression, and ncRNA expression is regulated in response to environmental chemicals. The mechanistic interactions between ncRNAs and CYPs associated with the toxicity and carcinogenicity of environmental chemicals are described in this review, focusing on microRNA-dependent CYP regulation. The role of long noncoding RNAs in regulating CYP expression is also presented and new avenues of research concerning this regulatory mechanism are described.
Hexavalent chromium [Cr (VI)] contributes a significant health risk and causes a number of chronic diseases and cancers. While the genotoxic and carcinogenic effects of hexavalent chromium exposure are explicit and better-characterized, the exact mechanism underlying the carcinogenic process of Cr (VI) is still a matter of debate. In recent years, studies have shown that epigenetic modifications, especially DNA methylation, may play a significant role in Cr (VI)-induced carcinogenesis. The aim of this review is to summarize our understanding regarding the effects of Cr (VI) on global and gene-specific DNA methylation.
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in lipid metabolism, cell proliferation, terminal differentiation, apoptosis, and inflammation. Although several cancer models have been suggested to explain PPARs' involvement in tumorigenesis, however, their role is still unclear. In this review, we examined associations of the different PPARs, polymorphisms and various types of cancer with a focus on gene-environment interactions. Reviewed evidence suggests that functional genetic variants of the different PPARs may modulate the relationship between environmental exposure and cancer risk. In addition, this report unveils the scarcity of reliable quantitative environmental exposure data when examining these interactions, and the current gaps in studying gene-environment interactions in many types of cancer, particularly colorectal, prostate, and bladder cancers.
Gold nanoparticles (AuNPs) have been previously shown to induce gut dysbiosis during colitis in mice, but the underlying mechanism is not clear yet. Here, we evaluated the effects of AuNPs (5 nm diameter, coated with tannic acid, polyvinylpyrrolidone or citrate) on H2O2 accumulation and pathogen antagonization by an intestinal strain of Lactobacillus gasseri under aerobic cultural conditions. AuNPs (0.65 mu g/mL) reduced over 50% of H2O2 accumulation by L. gasseri, and significantly inhibited the antagonistic action of L. gasseri on growth of four foodborne enteric pathogens, i.e. Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus in associative cultures.
Reactive Red 195 was detected from industrial waste samples electrochemically on graphene modified glassy carbon electrode (GCE), using both bare and surface changed GCE at different pH media from 1.0 to 13.0. The optimum pH was determined to be 4.0. RR 195 exhibited good linear responds at pH 4.0 on both electrode surfaces. Other parameters, such as accumulation potential, accumulation time, initial scan potential, pulse height, pulse width, and potential scan increment and scan rate are optimized and calibration plot was also derived on different concentrations of the dye. The stripping voltammetric behavior of dye exhibits very low limit of detection on graphene coated electrode (30 ppb). The adsorption of compound on GCE and graphene coated GCE are confirmed using atomic force microscopy studies.
Noble metal nanoparticles (NPs) and their hybrids have demonstrated a strong potential to mimic the catalytic activity of natural enzymes and diminish oxidative stress. There is a large space to explore the intrinsic catalytic activity of Rh NPs with respect to reactive oxygen species (ROS) scavenging. We found that Rh NPs can quench H2O2, (OH)-O-center dot, O-2(center dot-), O-1(2) and inhibit lipid peroxidation under physiological conditions. In vitro cell experiments proved that Rh NPs have great biocompatibility and protect cells from oxidative damage caused by H2O2. This study can provide important insights that could inform future biological applications.
Drinking mate, an infusion of the herb ilex paraguariensis, is very common in several South American countries, and has been associated with an increased risk of esophageal cancer. This increased risk may be attributed to drinking mate very hot, or to mate's potentially carcinogenic contaminants, such as polycyclic aromatic hydrocarbons (PAHs). Mate leaves are often dried via smoking, and therefore commercial samples may have high amounts of PAHs. We found 10 original articles that had measured PAHs in commercial dry samples, and nearly all found very high mass fractions. Most studies found benzo[a]pyrene mass fractions to be over 25 ng/g, and some found levels up to 600 ng/g. However, carcinogenic PAHs are often hydrophobic, and may not readily transfer into infusions. Seven articles studied transfer rates, and these rates varied from 1 to 50%, depending on the methods employed. Further careful studies of transfer rates in situations that mimic real life drinking of mate are recommended. Also, further studies of biological indicators of PAH exposure, particularly in randomized experiments, and analyzing DNA from tumor samples of mate drinkers are recommended.
Engineered nanomaterials may adversely impact human health and environmental safety by nano-bio-eco interactions not fully understood. Their interaction with biotic and abiotic environments are varied and complicated, ranging from individual species to entire ecosystems. Their behavior, transport, fate, and toxicological profiles in these interactions, addressed in a pioneering study, are subsequently seldom reported. Biological, chemical, and physical dimension properties, the so-called multidimensional characterization, determine interactions. Intermediate species generated in the dynamic process of nanomaterial transformation increase the complexity of assessing nanotoxicity. We review recent progress in understanding these interactions, discuss the challenges of the study, and suggest future research directions.
