In the last decade, several advancements have been made in omics technologies and they have been applied extensively in diverse research areas. Especially in toxicological research, omics technology can efficiently and accurately generate relevant data on the molecular dynamics associated with adverse outcomes. Toxicomics is defined as the combination of toxicology and omics technologies and encompasses toxicogenomics, toxicoproteomics, and toxicometabolomics. This paper reviews the trend of applying omics technologies to evaluate cadmium (Cd) toxicity in zebrafish (D. rerio). Cd is a toxic heavy metal posing several environmental concerns; however, it is being used widely in everyday life. Zebrafish embryos and larvae are employed as standard models for many toxicity tests because they share 71.4% genetic homology with humans. This study summarizes the toxicity of Cd on the nerves, liver, heart, skeleton, etc. of zebrafish and introduces detailed omics techniques to understand the results of the toxicomic studies. Finally, the trend of toxicity evaluation in the zebrafish model of Cd based on omics technology is presented.

Repeated health and environmental scandals, the loss of biodiversity and the recent burst of chronic diseases constantly remind us the inability of public authorities and risk assessment agencies to protect health and the environment. After reviewing the main shortcomings of our evaluation system of chemicals and new technologies, supported by some concrete examples, we develop a number of proposals to reform both the risk assessment agencies and the evaluation processes. We especially propose the establishment of an independent structure, a High Authority of Expertise, supervising, either at European level or at national level, all the evaluation agencies, and ensuring the transparency, the methodology and the deontology of the expertise. In addition to modifying the evaluation protocols, both in their nature and in their content, especially in order to adapt them to current pollutants such as endocrine disruptors, we propose a reform of the expertise processes based on transparency, contradiction, and greater democracy, including close collaboration between the institutional and scientific parties on the one hand and the whole civil society on the other. All the proposals we make are inspired by the desire to prevent, through appropriate mechanisms, the human, health, ecological, but also economic consequences of contemporary technological choices.

To develop a new simple and simultaneous purification method for mycotoxins in feeds and grains, magnetic nanoparticles (MNPs) conjugated with monoclonal antibodies (mAbs) against mycotoxins were used to separate aflatoxin B1 (AFB₁), zearalenone (ZEA) and deoxynivalenol (DON). For a single spike of each mycotoxin into the buffer solution (16% MeOH in PBS), mean recoveries were 93.1-95.0% for AFB₁ (5-20 ng/mL spiked), 87.2-96.0% for ZEA (125-500 ng/mL spiked) and 75.2-96.9% for DON (250-1,000 ng/mL spiked) by HPLC and ELISA. Recoveries of AFB₁ (20 ng/mL) and ZEA (500 ng/mL) simultaneously spiked into the buffer solution were 87.0 and 99.8%, respectively. Recovery rates of AFB₁/DON and DON/ZEA spiked simultaneously were 86.2%/76.6% and 92.0%/86.7%, respectively, at concentrations of 20 ng/mL AFB₁, 500 ng/mL ZEA, and 1,000 ng/mL DON. Recoveries using the novel mAb-MNP conjugated system in a buffer solution simultaneously spiked with AFB₁, ZEA and DON were 82.5, 94.6 and 73.4%, respectively. Recoveries of DON in animal feed were 107.7-132.5% at concentrations of 250-1,000 ng/g spiked in feed. The immunoaffinity chromatography (IAC) clean-up method was compared with the purification method using novel mAb-MNP. After fortification of animal feed with AFB₁ (5, 10 and 20 ng/g feed) and ZEA (125, 250 and 500 ng/g feed), AFB₁ and ZEA were purified using both the methods. In the case of the novel mAb-MNP conjugated system, mean recoveries for AFB₁ were 89.4, 73.1 and 88.3% at concentrations of 5, 10 and 20 ng/g feed, respectively. For ZEA, mean recoveries were 86.7, 85.9 and 79.1% at concentrations of 125, 250 and 500 ng/g, respectively. For IAC purification, recoveries were 42.9-45.1% for AFB₁ and 96.8-103.2% for ZEA. In conclusion, the present purification method using monoclonal antibodies conjugated to MNPs can be used for simple and simultaneous purification of mycotoxins from feed and maize.

We have recently highlighted the immunomodulatory effect of ethanol extract of Curcuma mangga Val. rhizomes. The current study was performed to investigate the teratogenic effects of C. mangga extract in Wistar rats. The C. mangga extract at doses of 100, 500 and 1000 mg/kg bw were administered to pregnant rats on day 6-15 of gestation. The litter size, length and birth weight as well as body weight of pregnant rats were determined to evaluate the teratogenic effects of C. mangga extract. External and skeletal malformations were also examined. The extract reduced the litter length compared to normal control (p<0.05). The average body weight gain of the pregnant rats also decreased. Resorption was observed after treatment with extract at the dose of 1000 mg/kg bw. The extract at the doses of 500 and 1000 mg/kg bw reduced litter birth weight and induced external and skeletal malformations. This demonstrates that ethanol extract of C. mangga has teratogenic effects in Wistar rats and should be used with caution in pregnancy.

In vivo phototoxicity testing is important for predicting drug-induced phototoxicity in humans. Currently, there is no internationally validated in vivo test method for the photosafety evaluation of pharmaceuticals. In this study, we evaluated the phototoxicity of systemically administered drugs using SD rats. We first determined the appropriate ultraviolet A (UVA) dose using 8-methoxypsoralen, a well-known phototoxic drug. Compared to lower and higher UVA doses, we found that a UVA dose of 10 J/cm² allowed for the detection of phototoxic responses in both a dose- and time-dependent manner. We next performed a phototoxicity study using seven pharmaceutical drugs which included known phototoxic and non-phototoxic drugs using a UVA dose of 10 J/cm². In order to improve the accuracy of our assessment, we evaluated both gross skin findings as well as histopathological findings. Using gross skin findings alone resulted in an accuracy of 85.7% which could be increased to 100% accuracy when the gross skin findings were combined with histopathological findings. This study suggests that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of systemically administered drugs in SD rats. In conclusion, we found that for studying drug-induced phytotoxicity, a 10 J/cm² UVA dose serves as the optimal radiation dose, and that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of the drugs.

Microplastics (MPs) have been recently recognized as a global environmental threat and its exposure as a risk factor to human health. Health effects through MPs exposure have been recently reported, especially through oral route of exposure. Since MPs could be exposed to humans through routes other than oral, this study was designed to evaluate whether MPs exposed through the inhalation route could be delivered to fetal mice and exhibit systemic toxicity. Polyethylene (PE) with 10-45 ㎛ diameter were administered at 0 (distilled water, vehicle control), 6 (low administration), and 60 (high administration) ㎍/mouse/day to 3 pregnant dams per group from gestational day 9 to postnatal day (PND) 7 through intratracheal instillation. Dams and neonates were sacrificed at PND 7 and blood was collected. Various neonatal organs including brain, lung, heart, stomach, intestine, kidneys, and ovaries were collected for histopathological observation and weight measurement. No influence of PE-MPs administration was observed on the number of offsprings born, but the body and organs' weight were heavier overall in the high administration group of dams and neonates than the other groups with statistical significance achieved in the heart and spleen weight. Level of serum acetylcholinesterase and glutathione peroxidase activity was decreased in the high administration group of dams and neonates compared with the other groups. Lung was the organ with highest number of PE-MPs present in the both administration groups of dams, and PE-MPs were also detected in liver and intestine of the high administration dams. Whereas, PND7 neonates showed accountable numbers of PE-MPs only in kidneys of the high administration group. Overall, the present study indicates that PE-MPs instilled intratracheally could be delivered to neonates from dams. Even though adverse effects from PE-MPs exposure during pregnant and lactational period are less prominent on both dam and neonate, potential of second-generation toxicity could be considered for further investigation.

Methylmercury is an environmental pollutant that induces potent neurotoxicity. We previously identified transcription factor 3 (TCF3) as a transcription factor that is activated in the brains of mice treated with methylmercury, and reported that methylmercury sensitivity was increased in cells in which TCF3 expression was suppressed. However, the mechanisms involved in the activation of TCF3 by methylmercury and in the reduction of methylmercury toxicity by TCF3 remained unclear. We found that treatment of mouse neuronal C17.2 cells with methylmercury increased TCF3 protein levels and promoted the binding of TCF3 to DNA consensus sequences. In cells treated with actinomycin D, a transcription inhibitor, an increase in TCF3 protein levels was also observed under methylmercury exposure. However, in the presence of cycloheximide, a translation inhibitor, methylmercury delayed the degradation of TCF3 protein. In addition, treatment with MG132, a proteasome inhibitor, increased TCF3 protein levels, and there was not significant increase in TCF3 protein levels by methylmercury under these conditions. These results suggest that methylmercury may activate TCF3 by increasing its levels through inhibition of TCF3 degradation by the proteasome. It has been previously reported that the induction of apoptosis in neurons is involved in methylmercury-induced neuronal damage in the brain. Although apoptosis was induced in C17.2 cells treated with methylmercury, this induction was largely suppressed by overexpression of TCF3. These results indicate that TCF3, which is increased in the brain upon exposure to methylmercury, may be a novel defense factor against methylmercury-induced neurotoxicity.

This study aimed to investigate the potential of Mangifera indica L. seed kernel extract, which is highly discarded by the global food processing industry, as a multifunctional bioactive ingredient for nutraceutical and cosmeceutical applications. Different extracting solvents were utilized, the extracts were then tested for their antioxidant activities using DPPH, ABTS radical scavenging assays, and inhibition of lipid peroxidation. Additionally, total phenolic content (TPC), total flavonoid content (TFC), and gallic acid content were elucidated using Folin-Ciocalteu and aluminum chloride colorimetric assays, as well as high performance liquid chromatography. The hydroethanolic extract (KMHE) exhibited the highest percentage yield, with the highest antioxidant activity owing to its high phenolic content. KMHE consisted of 773.66±9.42 mg GAE/g extract in TPC, 36.20±4.20 mg RU/g extract in TFC. Additionally, gallic acid was shown to be a major constituent of KMHE. KMHE was investigated for anti-tyrosinase, anti-hyaluronidase, anti-MMP-2, and anti-MMP-9 activities. Moreover, the anti-inflammatory effects of KMHE were studied in RAW 264.7 cells induced by nitric oxide and KMHE was shown to prevent DNA damage, indicating an inhibitory effect on cellular aging. KMHE showed outstanding anti-tyrosinase activity and was as potent an anti-hyaluronidase as gallic acid. Additionally, our results reveal notable anti-MMP-2 and anti-MMP-9 effects that were not significantly different from those of gallic acid. Furthermore, KMHE demonstrated 61.54±2.39% nitric oxide inhibition, with no cytotoxic effects, in RAW264.7 cells, and also prevented DNA damage in the human fibroblast BJ cell line with no cytotoxic effects. Therefore, KMHE could be a promising, natural multifunctional bioactive compound for nutraceutical and cosmeceutical applications.

This study aims at investigating the protective effects of flavonoid fractions of diosmin and hesperidin in mitigating sub-chronic lead acetate-induced biochemical, oxidative stress, and histopathological alterations in adult male Wistar rats. Forty animals were randomly assigned into five groups, each consisting of eight animals. Group I animals was treated with deionised water only, group II, IV, and V were administered lead acetate 90 mg/Kg body weight (1/20th of the LD₅₀), groups III, and IV was administered Daflon (100 mg/Kg), while group V was administered Daflon (200 mg/Kg), 30 min prior treatment with lead acetate. All treatments lasted for 42 days. Blood lead levels, electrolyte parameters, zinc protoporphyrin (ZPP) levels, activities of antioxidant enzymes, and histopathology of vital organs, were evaluated following standard practice. Sub-chronic lead acetate exposure induced a decrease in levels of serum electrolytes, and activities of antioxidant enzymes, while blood lead levels, ZPP, and malondialdehyde levels were increased. Lead exposure also instigated marked variation in histopathology of vital organs. Conversely, co-treatment with graded doses of daflon improved the levels of blood lead, electrolytes, ZPP, activities of antioxidant enzymes, and histopathology of vital organs. Data obtained from the current study indicate that rats exposed to sub-chronic doses of lead acetate show increased blood lead levels, electrolyte imbalance, alongside impairment in ZPP levels, activities of antioxidant enzymes, and histopathology, while pretreatment using daflon mitigated the ensued perturbations. This, therefore, suggests that consumption of foods enriched with flavonoid fractions of diosmin and hesperidin may be beneficial for individuals inhabiting lead-polluted environments.

Despite intensive research efforts in recent decades, cancer remains a leading cause of death worldwide. The chalcone family is a promising group of phytochemicals for therapeutic use against cancer development. Naturally-occurring chalcones, as well as synthetic chalcone analogues, have shown many beneficial biological properties, including anti-inflammatory, antioxidant, and anti-cancer activities. In this report, trans-chalcone (TChal) was found to increase cell death in breast cancer cells, assessed using high content screening. Subsequently, using antibody array analysis, TChal was found to increase heme oxygenase-1 (HO-1) expression in TChal-treated breast cancer cells. Blocking of HO-1 by siRNA in breast cancer cells diminished the effect of TChal on cell growth inhibition. TChal-fed mice also showed less tumor growth compared to vehicle-fed mice. Overall, we found that TChal increases HO-1 expression in breast cancer cells, thereby enhancing anti-tumorigenesis. Our results suggest that HO-1 expression could be a potential new target of TChal for anti-tumorigenesis in breast cancer.

Levels of organochlorine pesticides (OCPs) residues in tilapia fish and their health risk associated with the consumption of fish from Edko lake, Egypt were determined. The quick, easy, cheap, effective, rugged, and safe method (QuEChERS) was used for extraction and clean-up of 18 OCPs residues from fish followed by GC-ECD and GC-ITD analytical tools were employed for identification of OPs. Out of the 18 OCPs, only heptachlorepoxide, p,p-DDE, dieldrin, p,p-DDD, and endrin ketone were detected in muscles of fish with concentrations of 0.1144, 0.2119, 0.4352, 0.1196, and 0.1323 ㎍/Kg bw, respectively. Results of the risk assessment calculations showed that dieldrin had a health risk index of more than one. This means that there was a health risk to adults associated with the consumption of fish. On the other hand, heptachlorepoxide, p,p-DDE, p,p-DDD, and endrin ketone did not show any direct health risk. Contamination of fish, collected from Edko lake in Egypt, with residues of OCPs might pose health implications if fish were consumed fresh.