Food and Chemical Toxicology最新文献

Humans are exposed to complex mixtures of mycotoxins through diet. Despite the serious threat they pose, mycotoxin risk assessment often overlooks co-exposure. With the aim of filling this gap, the present study investigates the combined cytotoxicity of sterigmatocystin (STE), ochratoxin A (OTA) and patulin (PAT) in human tumour Neuroblastoma and healthy Mesenchymal Stem Cells three-dimensional (3D) spheroids. The range of concentrations tested (1.56–50 μM for STE, 0.78–25 μM for OTA and 0.15–5 μM for PAT) was selected considering the IC₅₀ values obtained in previous studies and the estimated dietary exposure of consumers. To ensure appropriate experimental conditions, assessments for single mycotoxins and their combinations were conducted simultaneously. The nature of the toxicological interactions among the mycotoxins was then defined using the isobologram analysis. Our results demonstrated increased cytotoxicity in mycotoxin mixtures compared to individual exposure, with abundance of synergistic interactions. These findings highlight that the co-occurrence of STE, OTA and PAT in food may increase their individual toxic effects and should not be underestimated. Moreover, the use of advanced culture models increased the reliability and physiological relevance of our results which can serve as a groundwork for formulating standardized regulatory approaches towards mycotoxin mixtures in food and feed.

Acute kidney injury (AKI) is a worldwide public health problem with high morbidity and mortality. Cisplatin is a widely used chemotherapeutic agent for treating solid tumors, but the induction of AKI restricts its clinical application. In this study, the effect of cisplatin on the expression of organic ion transporters was investigated through in vivo and in vitro experiments. Targeted metabolomics techniques were used to measure the levels of selected endogenous substances in serum. Transmission electron microscopy was used to observe the microstructure of renal tubular epithelial cells. Our results show that the toxicity of cisplatin on HK-2 cells or HEK-293 cells was time- and dose-dependent. Administration of cisplatin decreased the expression of OAT1/3 and OCT2 and increased the expression of MRP2/4. Mitochondrial damage induced by cisplatin lead to renal tubular epithelial cell injury. In addition, administration of cisplatin resulted in significant changes in endogenous substance levels in serum, including amino acids, carnitine, and fatty acids. These serum amino acids and metabolites (α-aminobutyric acid, proline, and alanine), carnitines (tradecanoylcarnitine, hexanylcarnitine, octanoylcarnitine, 2-methylbutyroylcarnitine, palmitoylcarnitine, and linoleylcarnitine) and fatty acids (9E-tetradecenoic acid) represent endogenous substances with diagnostic potential for cisplatin-induced AKI.

Arsenic is a metalloid found in the environment that causes toxic effects in different organs, mainly the liver. This study aimed to investigate the protective effects of epicatechin (EC), a natural flavonol, on glucose intolerance (GI) and liver toxicity caused by sodium arsenite (SA) in mice. Our findings showed that SA exposure led to the development of GI. Liver tissue damage and decreased pancreatic Langerhans islet size were also observed in this study. Mice exposed to SA exhibited hepatic oxidative damage, indicated by reduced antioxidant markers (such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione), along with elevated levels of thiobarbituric acid reactive substances. SA administration elevated the serum activities of liver enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Furthermore, notable increases in the levels of inflammatory and apoptotic markers (Toll-like receptor 4, nuclear factor-kappa B, tumor necrosis factor-α, nitric oxide, B-cell lymphoma-2, and cysteine aspartate-specific protease-3) were observed in the liver. Treatment of SA-exposed mice with EC considerably reversed these biochemical and histological changes. This study demonstrated the beneficial effects of EC in ameliorating SA-induced hyperglycemia and hepatotoxicity due to its ability to enhance the antioxidant system by modulating inflammation and apoptosis.

In recent decades, the toxicity of chiral pesticides to non-target organisms has attracted increasing attention. Cellular metabolic disorders are essential sensitive molecular initiating event for toxicological effects. BF is a typical chiral pesticide, and the liver is the main organ for BF accumulation. This study aimed to investigate the potential molecular mechanism of BF enantiomers' different toxic effects on L02 by a non-targeted metabolomic approach. Results revealed that the BF enantiomers exhibited different metabolic responses. In total, 51 and 36 differential metabolites were perturbed by 1S-cis-BF and 1R-cis-BF at the value of variable importance, respectively. When L02 were exposed to 1R-cis-BF, the significantly disturbed metabolic pathways were nicotinate and nicotinamide metabolism and pyrimidine metabolism. By comparison, more significantly perturbed metabolic pathways were received when the L02 were exposed to 1S-cis-BF, including glycine, serine and threonine metabolism, nicotinate and nicotinamide metabolism, arginine and proline metabolism, cysteine and methionine metabolism, glycerolipid metabolism, histidine metabolism, pyrimidine metabolism, amino sugar and nucleotide sugar metabolism and arginine biosynthesis. The results offer a new perspective in understanding the role of selective cytotoxicity of BF enantiomers, and help to evaluate the risk to human health at the enantiomeric level.

Ethylamine, ethanolamine and methylamine are biogenic amines (BA) - active metabolites that, despite having important biological functions, may accumulate at toxic concentrations in certain foods. Very little information exists on the toxicity of these BA in this context. This study provides new insights into their cytotoxicity with respect to a human intestinal epithelial cell line, as assessed using real-time cell analyzer technology. A preliminary evaluation of the cytotoxic mode of action was also performed. The present results show that only ethylamine was cytotoxic for these cells at food concentrations. These new data should help establish legal limits for these BA in foods.

Coconut Inflorescence Sap (CIS) is the sweet, oyster-white colored, non-fermented juice obtained from the immature inflorescence of the Coconut tree. Acetaminophen (N-acetyl-p-aminophenol, or paracetamol) is one of the most frequently used drugs worldwide as an antipyretic or analgesic. HepG2 cell lines were used as an experimental model for studying in vitro hepatotoxicity induced by Paracetamol. The present study aims to identify biologically active compounds of CIS using LCMS analysis and to elucidate the ameliorative potential of CIS in alleviating paracetamol-induced hepatotoxicity. LC-MS analysis revealed the presence of 17 bioactive compounds. HepG2 cells were pretreated with Paracetamol (20 mM) for inducing toxicity, and Silymarin at a concentration of 50 μg/ml was used as a standard drug. The morphological analysis and MTT assay showed effective recovery from toxicity in cells treated with CIS in a dose-dependent manner. CIS at 25 μg/ml potentially showed the highest percentage of inhibitory activity against the toxicity induced by paracetamol. The treatment with paracetamol significantly increased the indicators of liver toxicity - LDH, SGOT, SGPT, and Glut.S Transferase in the media.CIS administration also increased the total protein levels, SOD, and Catalase activity. The morphological analysis, MTT assay, cytocompatibility studies, determination of enzymatic activities, etc., confirms the significant hepatoprotective efficacy of CIS.

With the growing importance of alternative test methods that implement the 3Rs principles (Reduction, Refinement and Replacement) and the global importance of biological safety assessment data for medical devices is increasing. We have developed and optimized the ‘KeraSkin™ Skin Irritation Test (KeraSkin™ SIT) for medical device’ for regulatory application in biological evaluation according to ISO 10993-23. We conducted a round robin study to optimize and evaluate the performance of KeraSkin™ SIT for medical devices using KeraSkin™ Reconstructed Human Epidermis (RhE), which is developed and manufactured in Korea. This round robin study was performed to assess the transferability, reproducibility (within and between laboratories) and predictive capacity in 1 lead laboratory and 3 participating laboratories based on OECD Guidance Document 34. The predictive capacity, the results showed 83.3 % of sensitivity, 100 % of specificity and 91.6 % of accuracy. In conclusion, the results demonstrate that ‘KeraSkin™ SIT for medical device’ provides a robust test method for detecting irritant activity of medical device extracts and can be utilized for identifying low levels of potent irritants in medical device extracts. Therefore, it fulfills the requirements to be included as a ‘me-too’ test method to EpiDerm™ and SkinEthic™ skin irritation test in ISO 10993-23.