Photodegradation enhances the toxic effect of anthracene on skin.

Anthracene, a polycyclic aromatic hydrocarbon (PAH), is a widespread environmental pollutant that poses potential risks to human health. Exposure to anthracene can result in various adverse health effects, including skin-related disorders. Photo exposure sufficiently removes the anthracene from the environment but also generates more degradation products which can be more toxic. The goal of this study was to assess the change in anthracene dermotoxicity caused by photodegradation and understand the mechanism of this change. In the present study, over 99.99% of anthracene was degraded within 24 h of sunlight exposure, while producing many intermediate products including 9,10-anthraquinone and phthalic acid. The anthracene products with different durations of photo exposure were applied to 2D and 3D human keratinocyte cultures. Although the non-degraded anthracene significantly delayed the cell migration, the cell viability and differentiation decreased dramatically in the presence of the photodegraded anthracene. Anthracene photodegradation products also altered the expression patterns of a number of inflammation-related genes in comparison to the control cells. Among these genes, il1a, il1b, il8, cxcl2, s100a9, and mmp1 were upregulated whereas the tlr4 and mmp3 were downregulated by the photodegraded anthracene. Topical deliveries of the photodegraded and non-degraded anthracene to the dorsal skin of hairless mice showed more toxic effects by the photodegraded anthracene. The 4-hour photodegradation products of anthracene thickened the epidermal layer, increased the dermal cellularity, and induced the upregulation of inflammatory markers, il1a, il1b, s100a9, and mmp1. In addition, it also prevented the production of a gap junction protein, Connexin-43. All the evidence suggested that photodegradation enhanced the toxicities of anthracene to the skin. The 4-hour photodegradation products of anthracene led to clinical signs similar to acute inflammatory skin diseases, such as atopic and contact dermatitis, eczema, and psoriasis. Therefore, the potential risk of skin irritation by anthracene should be also considered when an individual is exposed to PAHs, especially in environments with strong sunlight.

The changes and correlation of IL-6 and oxidative stress levels in RAW264.7 macrophage cells induced by PAHs in PM2.5.

The objective of this study was to investigate the effects of anthracene (Ant) with 3 rings, benzo[a]anthracene (BaA) with 4 rings and benzo[b]fluoranthene (BbF) with 5 rings in fine particulate matter (PM2.5) at different exposure times (4 h and 24 h) and low exposure levels (0 pg/mL, 0.1 pg/mL, 1 pg/mL, 100 pg/mL and 10,000 pg/mL) on RAW264.7 cells. The changes of interleukin-6 (IL-6) and oxidative stress levels in RAW264.7 cells were investigated by methyl-thiazolyl-tetrazolium (MTT) and enzyme-linked immunosorbent assay (ELISA). Pearson correlation analysis was used to analyze the correlation between variables. Ant, BaA and BbF induced the secretion of IL-6 and the occurrence of oxidative stress in RAW264.7 cells. The inflammatory effect and oxidative damage were exacerbated with prolonged exposure time, increasing exposure concentration and increasing number of PAH rings. At the same time, IL-6 was found to have a certain correlation with the levels of ROS, MDA and SOD. Exposure to atmospheric PAHs at low concentrations can also produce toxic effects on cells, IL-6 and oxidative stress work together in cell damage. The study is expected to provide a theoretical and experimental basis for air pollution control and human health promotion.

Integration approach of transcriptomics and metabolomics reveals the toxicity of Anthracene and its chlorinated derivatives on human hepatic cells.

Polycyclic aromatic hydrocarbons (PAHs) and Chlorinated PAHs (Cl-PAHs) are ubiquitous environmental contaminants. The toxicological information of anthracene (Ant) and its chlorinated derivatives is quite limited. In this study, an integrated metabolomic and transcriptomic analysis approach was adopted to assess the toxic effects triggered by Ant and its chlorinated derivatives, 2-chloroanthracene (2-ClAnt) and 9,10-dichloroanthracen (9,10-Cl2Ant), at human-relevant levels on human normal hepatocyte L02 cells. The cell viability test showed no significant effects on the viability of L02 cells exposed to Ant, 2-ClAnt and 9,10-Cl2Ant at doses of 5-500 nM for 24 h. However, based on transcriptomic analysis, Ant, 2-ClAnt and 9,10-Cl2Ant exposure at human-relevant levels obviously perturbed global gene expression in L02 cells and induced the differential expression of several genes related to cancer development. As the number of genes related to cancer development altered by 9,10-Cl2Ant is the largest, 9,10-Cl2Ant posed greater risks of tumor development than Ant and 2-ClAnt did. Metabolomics analysis demonstrated that Ant, 2-ClAnt and 9,10-Cl2Ant caused significant metabolic perturbation in L02 cells. Pathway enrichment analysis indicated that Ant, 2-ClAnt and 9,10-Cl2Ant mainly perturbed the lipid metabolism and nucleotide metabolism pathway. However, 9,10-Cl2Ant caused a wider perturbation to metabolic pathways than Ant and 2-ClAnt did. In addition, dysregulation of nucleotide metabolism perturbed by Ant, 2-ClAnt and 9,10-Cl2Ant may be associated with the genomic instability and further carcinogenesis.

Size effect of polystyrene microplastics on the accumulation of anthracene for Java medaka (Oryzias javanicus).

Pollution by microplastics in aquatic ecosystems is a worldwide problem, and the role of microplastics as vectors of pollutants has been a concern. Although small microplastics are thought to have a greater effect than large microplastics as vectors of pollutants, the impact of the size of microplastics on their ability to serve as vectors of pollutants has not been quantified. In this study, we conducted the 14-day experiment (7 days of exposure and 7 days of depuration) with polystyrene microplastics (2-µm or 10-µm diameter) and anthracene. On the last day of the exposure period, the concentration of anthracene in the muscle of Java medaka exposed to both anthracene and 2-µm polystyrene microplastics was the highest (47.4 ± 15.2 µg/g-muscle) of any group, followed by the group exposed to both anthracene and 10-µm polystyrene microplastics (23.0 ± 4.2 µg/g-muscle) and the group exposed to only anthracene (11.2 ± 2.2 µg/g-muscle). These results demonstrated that the size of microplastics was a critical determinant of their ability to serve as vectors of anthracene. The concentrations of anthracene and fine microplastics in the environment are sufficiently low that the effect of microplastics as vectors of anthracene may be observed only under experimental conditions that are unlikely to occur in the present environment. However, because pollution by plastics is expected to become more serious in the future, careful thought and proactive action will be needed to ensure that the impact of microplastics as vectors of pollutants does not become demonstrable under future environmental conditions.

New Insights into the Phototoxicity of Anthracene-Based Chromophores: The Chloride Salt Effect†.

Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I- > Br- > F-). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (•OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced •OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that •OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced N1-(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized •OH and singlet oxygen (1O2) production over no-salt controls. Considering the relatively high levels of Na+, K+, and Cl- ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons in vivo.

Combined effects of microplastics and benz[a]anthracene on cardiotoxicity in zebrafish (Danio rerio) larvae: Size matters.

The size of microplastics (MPs) plays an important role in combined toxic effects including synergistic or antagonistic effects. However, the influence of the size of MPs on the combined toxicity of contaminants remains unclear. In this study, we employed a zebrafish model to investigate the effects of MP size on the combined toxicity of benz[a]anthracene (BaA), a representative polyaromatic hydrocarbon, using three different sizes of polystyrene MPs (PSMPs) (0.2, 1.0, and 10 µm). Treatment of all groups did not result in any mortality of the zebrafish larvae. However, small-sized PSMPs (0.2 µm) enhanced the toxic effect of BaA in larvae such as cardiac defect and disruption of vessel formation. Medium-sized PSMPs (1.0 µm) were boundary in terms of the combined toxic effect; however, large-sized PSMPs (10 µm) alleviated the cardiotoxicity of BaA, including cardiac defect, ROS levels, and cell death. The combined effects showed a correlation with the body burden of MPs and BaA in larvae according to particle size (in the order of 0.2 µm > 1.0 µm > 10 µm). The synergistic effects occurred likely because the small PSMPs facilitated the body burden of BaA, induced excessive ROS by Ahr-mediated activity, and caused cell death in the heart, resulting in increased heart defects in the larvae. In contrast, large PSMPs abated the combined toxic effect through decreased body burden, whereas medium PSMPs form a boundary in combined effects. Therefore, the combined toxic effects of MPs are dependent on their size, which plays an important role in the transport and accumulation of environmental pollutants.

Morphological and antioxidant responses of Cicer arietinum L. genotypes exposed to combination stress of anthracene and sodium chloride.

Various mutagenic, carcinogenic pollutants such as Polycyclic Aromatic Hydrocarbons (PAHs) are released into the environment posing a negative effect on plant metabolism. All the pollutants that are emitted into the atmosphere, ultimately find their way into the plant. Soil salinity stress is one of the major determinants of crop productivity. Different plants respond differently to different abiotic stress present alone or in combination. One such combination of abiotic stress is PAHs and salinity stress. The present research aims to study the effect of the application of NaCl and Anthracene alone and in various combinations on two chickpea genotypes GPF2 and PDG4. A 21 days laboratory experiment was conducted in petriplates and growth pouches. Different concentrations of NaCl and Anthracene were given to two chickpea genotypes viz. GPF2 and PDG4, alone as well as in combinations to study morphological, physiological and antioxidant responses. Results obtained were further analyzed by using various statistical measures such as Principle Component Analysis and Two-way ANOVA. Results indicated that under the dual presence of NaCl and Anthracene, GPF2 exhibited higher activities of antioxidant enzymes and was shown to have a negative correlation with plant height and chlorophyll content. Based on the results of the present investigation, it was concluded that GPF2 was a better performing chickpea genotype towards the combined presence of Anthracene and NaCl as compared to PDG4.

The overlooked toxicity of environmentally persistent free radicals (EPFRs) induced by anthracene transformation to earthworms (Eisenia fetida).

Environmentally persistent free radicals (EPFRs) as intermediate products exist widely in the PAHs-contaminated soils, but toxicity assessment associated with EPFRs for terrestrial invertebrates remains unclear. Using the model organism Eisenia fetida, we compared the adverse effects among anthracene (ANT), anthraquinone (ANQ), and EPFRs induced by ANT transformation on clay surfaces. Our results showed that EPFRs-exposed earthworms experienced histopathological damage, which was more severe than ANT and ANQ-exposed earthworms. The source of EPFRs damage was associated with the obvious dysbiosis of reactive oxygen species in earthworms. Specifically, EPFRs trigged more severe antioxidant responses and oxidative damages (e.g., membrane lipid and DNA injury) in comparison with ANT and ANQ exposure, as evidenced by the values of integrated biomarker response (IBR) following the order of EPFRs (14.5) > ANT (12.8) > ANQ (10.9). Moreover, high-throughput sequencing found that EPFRs induced dramatic changes in the composition and structure of earthworm gut microbiota, which may involve immune and metabolism dysfunction, in turn aggravated EPFRs toxicity. Overall, the obtained information highlights the more severe injury of EPFRs to terrestrial organisms, deserving more attentions for the assessment of potential risks associated with radical intermediates in PAHs-contaminated soils.

Hypericin, a medicinal compound from St. John's Wort, inhibits genotoxicity induced by mutagenic agents in V79 cells.

This study evaluated the cytotoxic, genotoxic, and the modulatory effects on DNA damage of hypericin in Chinese hamster lung fibroblasts (V79 cells). The hypericin is a natural polycyclic quinone, mainly extracted from St. John's Wort (Hypericum perforatum L.). Along with hyperforin, the hypericins are responsible for the antidepressant activity of St. John's Wort. Cytotoxicity was assessed by the XTT colorimetric assay and the nuclear division index (NDI). The genotoxic activity was studied by the micronucleus test at concentrations of 30, 60, 120, and 240 µg/mL. Mutagenic agents, methyl methanesulfonate (MMS, 44 µg/mL), doxorubicin (DXR, 0.5 µg/mL), and etoposide (VP16, 1 µg/mL) were used in combination with different concentrations of hypericin in order to evaluate the modulatory effect on DNA damage. Results showed that the hypericin was cytotoxic at concentrations above 156.2 µg/mL and genotoxic above 120 µg/mL. The hypericin significantly reduced DNA damage frequency induced by DXR, at concentrations of 30 and 60 µg/mL, and MMS at a concentration of 30 µg/mL, but was unable to reduce damage when combined with VP-16. These results demonstrate the non-photoactivated hypericin toxicological safety limits, its protective effect on DNA damage and provide a basis for future studies that may characterize better its chemopreventive mechanism.

Endothelial barrier dysfunction induced by anthracene and its nitrated or oxygenated derivatives at environmentally relevant levels.

Polycyclic aromatic hydrocarbons (PAHs) are epidemiologically associated with cardiovascular diseases characterized by early key events involving in the disruption of endothelial barrier function. Whether PAHs can induce adverse cardiovascular outcome by directly destabilizing endothelial barrier function remains elusive. Herein, we investigated the effect of anthracene (ANT), 9-nitroanthracene (9-NANT), and 9,10-anthraquinone (9,10-AQ) on vascular endothelial barrier functions in human umbilical vein endothelial cells (HUVECs). The integrity of endothelial barrier in HUVECs was disturbed with a 1.15-1.42 fold increase in fluorescein leakage, and 21.8%-58.3% downregulated transendothelial electrical resistance. ANT, 9-NANT and 9,10-AQ promoted paracellular gap formation as revealed by transmission electron microscope. The disrupted cell junctions after 24 h exposure to ANT, 9-NANT and 9,10-AQ at 0.01 µM were indicated by the downregulated mRNA expression of vascular endothelial cadherin (VE-cadherin), zona occludens-1 (ZO-1) and occludin by 33.2%-71.4%, 19.1%-21.0%, and 31.9% respectively, and the downregulated protein expression of ZO-1 and occludin, and by the internalization of VE-cadherin. We demonstrated that ANT and its derivatives at environmentally relevant concentrations induced endothelial barrier dysfunction via the disruption of cell junctions, providing essential in vitro evidence on the association with their adverse cardiovascular outcomes.

Influence of polystyrene microplastics on the volatilization, photodegradation and photoinduced toxicity of anthracene and pyrene in freshwater and artificial seawater.

In this study, the influences of polystyrene microplastics (PS MPs) on the volatilization, photodegradation and photoinduced toxicities of anthracene and pyrene were determined in freshwater and artificial seawater. The PS MPs reduced the volatilization of anthracene and pyrene, and the volatilization reduction was highly dependent on the PS MPs sizes and concentrations. The PS MPs increased the photodegradation kinetics (kp) of anthracene by promoting 1O2 generation and altered the photodegradation pathways through OH attack of the photodegradation byproducts. However, the kp of pyrene was decreased by PS MPs suppressing the transfer of electrons from excited pyrene to oxygen. The PS MPs modified the pathways of pyrene photodegradation via OH attack of the photodegradation byproducts. Due to light shielding by DOM and/or PS MPs aggregates in seawater, the modification of the photodegradation pathways of anthracene and pyrene by PS MPs was hardly happened in seawater compared with in freshwater. By changing the concentrations of anthracene or pyrene and their photodegradation byproducts, the PS MPs greatly affected the photoinduced toxicities of anthracene and pyrene to Selenastrum capricornutum and Phaeodactylum tricornutum. The influences of PS MPs on the volatilization, photodegradation and photoinduced toxicity of anthracene and pyrene are important and should be carefully considered during environmental risk assessments of anthracene and pyrene.

Lethal, behavioral, growth and developmental toxicities of alkyl-PAHs and non-alkyl PAHs to early-life stage of brine shrimp, Artemia parthenogenetica.

Alkyl-PAHs are the predominant form of PAHs in crude oils which are supposed to demonstrate different toxicities compared to non-alkyl PAHs. Little information is available about the toxicity of alkyl-PAHs on marine Artemia. This study addressed and compared the lethal, behavioral, growth and developmental toxicities of three alkyl-PAHs, namely 3-methyl phenanthrene (3-mPhe), retene (Ret) and 2-methyl anthracene (2-mAnt), to their non-alkyl forms, phenanthrene (Phe) and anthracene (Ant) using Artemia parthenogenetica (nauplii, <24 h) as test organism following a 48 h and a 7 d of exposure, respectively. Benzo-a-pyrene (Bap) was selected as a reference toxicant for the comparison with the above alkyl-PAHs and non-alkyl PAHs. Results showed that for all tested endpoints, A. parthenogenetica nauplii had the highest sensitivity to Bap while Ant had no significant effect on nauplii survival or development within given concentrations. Considering the aqueous freely dissolved PAH concentrations, the 48 h-LC50 (survival), 48 h-EC50 (immobility) and 7 d-LC10 (survival) of Bap were calculated as 0.321, 0.285 and 0.027 µg/L, respectively, which were twofold to fivefold lower than those of Phe, 3-mPhe, Ret, Ant and 2-mAnt. A higher acute toxicity of alkyl-PAHs (3-mPhe and 2-mAnt) than their non-alkyl forms (Phe and Ant) was observed. Not limited to Phe, the common non-polar narcotic mode of action was also observed for Bap, 3-mPhe, Ret and 2-mAnt, which was evident by the inhibited mobility of nauplii. The decreased body lengths were found for all PAH treatments compared to the solvent control, whereas instar retardations were only found in nauplii exposed to Bap, Phe and Ret. Our findings emphasized the sensitivity differences of A. parthenogenetica nauplii to selected alkyl PAHs and non-alkyl PAHs and confirmed the application of lethal, behavioral and growth indicators in the toxicity evaluation of selected PAHs other than Ant. However, the distinct toxicities of these PAHs suggested other toxic modes of action may play more important roles apart from narcotic mode of action and need to be elucidated in future studies. In addition, a strong correlation between the body length and the instar of A. parthenogenetica nauplii was observed for each PAH exposure, suggesting that body length can be representative for both growth and developmental indicators during biological monitoring of PAH pollution in marine environment.

Application of HepG2/C3A liver spheroids as a model system for genotoxicity studies.

HepG2 cells continue to be a valuable tool in early drug discovery and pharmaceutical development. In the current study we develop a 3D in vitro liver model, using HepG2/C3A cells that is predictive of human genotoxic exposure. HepG2/C3A cells cultured for 7-days in agarose-coated microplates formed spheroids which were uniform in shape and had well defined outer perimeters and no evidence of a hypoxic core. Quantitative real-time-PCR analysis showed statistically significant transcriptional upregulation of xenobiotic metabolising genes (CYP1A1, CYP1A2, UG1A1, UGT1A3, UGT1A6, EPHX, NAT2) and genes linked to liver function (ALB, CAR) in 3D cultures. In response to three model pro-genotoxicants: benzo[a]pyrene, amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-aminoanthracene (2-AA), we observed further transcriptional upregulation of xenobiotic metabolising genes (CYP1A1, CYP1A2, NAT1/2, SULT1A2, UGT1A1, UGT1A3) compared to untreated spheroids. Consistent with this, spheroids were more sensitive than 2D monolayers to compound induced single- and double- stranded DNA-damage as assessed by the comet assay and γH2AX phosphorylation respectively. In contrast, levels of DNA-damage induced by the direct acting mutagen 4-nitroquinoline N-oxide (4NQO) was the same in spheroids and monolayers. In support of the enhanced genotoxic response in spheroids we also observed transcriptional upregulation of genes relating to DNA-damage and cellular stress response (e.g. GADD45A and CDKN1A) in spheroids. In conclusion, HepG2/C3A 3D spheroids are a sensitive model for in vitro genotoxicity assessment with potential applications in early stage drug development.

Persistent Free Radicals from Low-Molecular-Weight Organic Compounds Enhance Cross-Coupling Reactions and Toxicity of Anthracene on Amorphous Silica Surfaces under Light.

Polycyclic aromatic hydrocarbon (PAH) contamination has raised great environmental concerns, while the effects of low-molecular-weight organic compounds (LMWOCs) on PAH photodegradation at amorphous silica (AS)/air interfaces have been largely ignored. In this study, the phototransformation of anthracene (ANT) at amorphous silica (AS)/air interfaces was investigated with the addition of LMWOCs. ANT removal was attributed to •OH attacking and the energy transfer process via 3ANT*. Light irradiation induced the fractured ≡SiO• or ≡Si• generation on AS surfaces, which could react with absorbed H2O and O2 to generate •OH and further yield a series of hydroxylated products of ANT. The presence of citric acid and oxalic acid improved •OH generation and enhanced ANT removal by 1.0- and 2.2-fold, respectively. For comparison, the presence of catechol and hydroquinone significantly decreased ANT removal and produced coupling products. The results of density functional theory calculations suggest that persistent free radicals (PFRs) on AS surfaces from catechol or hydroquinone after •OH attacking prefer to cross-couple with ANT via C-C bonding rather than self-couple. Dianthrone and cross-coupling products might possess higher ecotoxicity, while hydroxylated products were less ecotoxic than their parent compounds based on Ecological Structure Activity Relationships (ECOSAR) estimation. The results of this study revealed the potential ecotoxicity of PAH-adsorbed particulates coexisting with LMWOCs and also provided a new insight into PAH transformation through PFR pathways.

Nematode traits after separate and simultaneous exposure to Polycyclic Aromatic Hydrocarbons (anthracene, pyrene and benzo[a]pyrene) in closed and open microcosms.

The majority of experimental studies carried out to date, regarding the effects of pollutants on meiofauna have been conducted by means of closed systems, and rarely using open ones. The current work explored the impact of three Polycyclic Aromatic Hydrocarbons (PAHs), anthracene, pyrene and benzo[a]pyrene, applied alone or combined, on meiobenthic nematodes using both systems. The results revealed that single PAHs impacted the nematofauna similarly in closed or open systems with a higher toxicity observed for benzo[a]pyrene. However, the closed microcosms contaminated with PAHs became organically enriched, resulting in more non-selective deposit feeders and omnivores-carnivores. Taxonomic and functional effects related to combinations of PAHs were close to those of individual treatments in closed systems, however, for open ones, the outcomes were different. The caudal morphology influenced the response of taxa during their avoidance/endurance of hydrocarbons in open systems where the effects of PAHs mixtures appeared not only additive but also synergetic. Based on the results of the study, the use of open systems is preferred to closed ones as the research outcomes were more accurate and representing better conditions prevailing in nature.

Anticancer activity of Vicenin-2 against 7,12 dimethylbenz[a]anthracene-induced buccal pouch carcinoma in hamsters.

Buccal mucosa carcinoma is a significant cause of death in developing nations. Vicenin-2 is a significant bioactive compound found in Ocimum sanctum Linn or Tulsi that possesses several pharmacologic properties. Our focus is to understand the possible impact of Vicenin-2 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral carcinogenesis in hamsters. Buccal carcinoma was induced by treatment with carcinogenic DMBA, three times a week for 14 weeks. We determined 100% tumor incidence, abnormal tumor volume, inclined tumor burden, and deduced body weight in DMBA-induced oral squamous cell carcinoma (OSCC) hamsters. The upregulation of cytokine levels (interleukin [IL]-6, IL-1ß, and tumor necrosis factor-alpha [TNF-α]) was observed in DMBA-induced OSCC hamsters. Moreover, dysplastic, hyperplastic, and squamous cell carcinoma was identified in the DMBA-induced OSCC hamsters. The diminished activities of lipid peroxidation and enzymatic/nonenzymatic antioxidants were observed in DMBA-induced hamsters. Furthermore, the high expression of proliferating cell nuclear antigen (PCNA), Cyclin-D1, and Bcl-2, and attenuated Bax expression were observed in DMBA-induced hamsters. Our study results explored that Vicenin-2 (30 mg/kg) treated with DMBA-brushed hamsters averted tumor incidence, improved the antioxidant status, and inhibited lipid peroxidation. Moreover, Vicenin-2 inhibited the immunohistochemical expression of PCNA, Cyclin-D1, and Bcl-2, and significantly restored apoptotic Bax levels. The Vicenin-2 treatment prevents the lesion formation in the oral epithelium of the DMBA-induced hamsters. The Vicenin-2 treatment potentially halts the proinflammatory cytokines (IL-6, IL-1ß, and TNF-α) production in OSCC hamsters. Thus, we proved that Vicenin-2 prevents DMBA-induced buccal carcinogenesis in hamsters via improving antioxidants by modulating apoptotic and cytokines signaling pathways.

Dietary ingestion of 2-aminoanthracene (2AA) and the risk for type-1 diabetes (T1D).

Type 1 diabetes (T1D) is an autoimmune disorder caused by the destruction of insulin-secreting ß-cells.T1D is on the rise around the world. Exposure to polycyclic aromatic hydrocarbons (PAHs) including 2-aminoanthracene (2AA) is considered a contributor to TID increase. The contribution of the ingestion of 2AA toward T1D vulnerability is examined. 2AA is found in a variety of household products. Juvenile male Sprague Dawley rats ingested various amounts of 2AA contaminated diet for 12 weeks. Results showed marginal reduction in body weight gain for the 100 mg/kg treated animals. Glucose tolerance test (GTT) indicated no changes at six weeks. However, at week 12, both treated groups had higher levels of blood glucose than the control group. Serum insulin concentration was elevated in the 50 mg/kg group while reduced in the 100 mg/kg animals. Serum lactate dehydrogenase activity was elevated in treated groups. Evaluation of pancreatic inflammatory cytokines revealed overexpression of IL-1B, IL-6, and IL-7. Apoptotic genes in the pancreas of exposed rats were overly expressed. Histopathology and insulin immunohistochemistry data showed the presence of mesenteric vessels surrounded by lymphocyte and enlarged size of islet cells respectively in the high dose group. These results suggest 2AA ingestion may enhance T1D development.

Possible Roles of Proinflammatory Signaling in Keratinocytes Through Aryl Hydrocarbon Receptor Ligands for the Development of Squamous Cell Carcinoma.

Aryl hydrocarbon receptor (AhR) provides a deeper insight into the pathogenesis of cutaneous squamous cell carcinoma (cSCC). AhR ligands, such as 6-formylindolo[3,2-b] carbazole (FICZ), and 7,12-Dimethylbenz[a]anthracene (DMBA), constitute major substrates for the cytochrome P450 (CYP) family, and influence the expression of various cytokine genes, including IL-17 and IL-23-related genes via the AhR. On the other hand, proinflammatory cytokines could drive tumor progression through the TRAF-ERK5 signaling pathway in cSCC. From the above findings, we hypothesized that AhR ligands might enhance the mRNA expression of proinflammatory cytokines via the AhR, leading to the development of cSCC. The purpose of this study was to investigate (1) the immunomodulatory effects of FICZ and DMBA on normal human keratinocytes (NHKCs), focusing on IL-17, and related cytokines/chemokines (IL-23, IL-36γ, and CCL20), (2) the expression of these factors in AhR-dependent pathways using a two-stage chemically induced skin carcinogenesis mouse model, and (3) the expression of these factors in lesion-affected skin in cSCC. Both FICZ and DMBA augmented the expression of CYP1A1, p19, CCL20, and IL-36γ mRNA in NHKCs in vitro. Moreover, the mRNA expression of these proinflammatory factors, as well as IL-17, in mouse cSCC is significantly decreased in the AhR-(fl/fl) Krt5-(Cre) mice compared to wild type mice, leading to a decrease in the number of developed cSCC lesions. Furthermore, CCL20, IL-23, as well as IL-17, are detected in the lesion-affected skin of cSCC patients. Our study demonstrates a possible mechanism for the development of cSCC involving AhR-mediated signaling by epidermal keratinocytes and recruitment of Th17 cells.

Quantifying the vector effects of polyethylene microplastics on the accumulation of anthracene to Japanese medaka (Oryzias latipes).

To better assess the risk of microplastics (MPs) as a vector for contaminants, it is essential to understand the relative importance of MPs compared to other pathways for chemical transfer as well as the consequences of co-exposure. In this study, we exposed Japanese medaka (Oryzias latipes) to anthracene (ANT, 0.1 mg/L) in the presence or absence of pristine polyethylene MPs (PE-MPs, 106 beads/L), to quantify the vector effect of PE-MPs on ANT accumulation. Under the ANT-MPs co-exposure conditions, PE-MPs rapidly accumulated in the gastrointestinal tract of the medaka during a 14-day uptake phase, with an average bioconcentration factor of 171.4 L/kg. The PE-MPs could absorb and accumulate approximately 70 % of the ANT from the water sample. The PE-MPs changed the pharmacokinetic profile of ANT in medaka by decreasing both the uptake and depuration rate constants. The one compartment with first-order elimination model estimated that the amounts of ANT in the water phase and absorbed by PE-MPs (i.e., a vector effect) contributed about 67 % and 33 % of the ANT accumulation in medaka, respectively. At the end of the uptake (exposure) phase, however, the presence of PE-MPs did not significantly alter the final ANT concentrations in the fish body or alter the behavioral impacts of ANT. Thus, PE-MPs ingestion may act as a vector to concentrate and transfer ANT to medaka, but the presence of these particles may have limited adverse effects on fish under co-exposure systems of the type used in this study.

Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats.

Breast cancer is among most common form of cancer worldwide. It is also the major cause of death in female cancer patient around the world. Despite various therapeutic measures, it remains associated with high mortality rate. Aegle marmelos (L.) Correa has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, there are very limited reports regarding its anticancer activity. Thus, the present research work has been aimed to study the anticancer activity of Aegle marmelos fruit extract on 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer in rats. Female Charles Foster rats, 55-60 days old weighing around (150 ± 10 g) were used for the study and were induced DMBA (20 mg/mL dissolved in Olive oil) orally. After the development of breast tumors (about 0.5 cm), the rats were treated with Aegle marmelos ethanolic fruit pulp extract (200 mg/kg b.w./day) orally for 5 weeks and then volume of tumor was measured. Aegle marmelos treatment showed significantly reduced mammary tumor volume (P < 0.05), along with significant reduction (P < 0.0001) in the different serum biomarkers such as TNF-α level, serum malondialdehyde (MDA) level and glucose levels. Significant (P < 0.0001) improvement in both, the kidney and liver serum biomarker parameters were also observed after the treatment with Aegle marmelos ethanolic fruit pulp extract. From the entire study, taking everything into account it can be interpreted that Aegle marmelos ethanolic fruit pulp extract possesses anti-proliferative activity by suppressing the progression of breast tumors in rat model. The plant extract also possesses hepato-renal protective effect. Hence, it can be targeted as novel and safe anti-cancer drug against breast cancer.