Food and Chemical Toxicology最新文献

The causal relationship between the artificial sweetener aspartame and ovarian cancer (OC), a highly lethal malignancy, remains unclear. This study, therefore, employed a multi-omics approach to investigate this causal link and its potential mechanisms. First, a Mendelian Randomization (MR) analysis indicated that genetically predicted aspartame intake is associated with an increased risk of OC (OR = 2.10, 95% CI: 1.06-4.18). Next, by integrating network toxicology with machine learning algorithms (LASSO, SVM, and Random Forest), we identified AURKA, CCND1, and RAD51 as potential core target genes. Further validation using multi-omics data from bulk and single-cell RNA sequencing confirmed that these three genes are upregulated in OC tissues. A subsequent MR analysis also provided causal evidence that high expression of CCND1 increases the risk of OC. Furthermore, molecular docking simulations showed that aspartame could form stable bonds with all three target proteins. Finally, in vitro experiments demonstrated that aspartame significantly promoted the malignant phenotypes of OC cells and regulated the expression of these core genes. In conclusion, this study suggests that aspartame may promote ovarian cancer development, potentially by upregulating the expression of key genes such as AURKA, CCND1, and RAD51. These findings provide new evidence for evaluating the safety of aspartame.

Seafood may accumulate heavy metals (HMs) from environmental sources, posing potential health risks through dietary intake. This study aimed to assess the health risk associated with dietary intake of Hg, Cd, As and Zn from selected seafood available in Poland. In this study, a total 51 samples of shrimp and squid were analyzed. The metals content was determined using such analytical methods as ET-AAS with a graphite furnace in the case of Cd, ICP-OES in the case of As and Zn, and CV-AFS in the case of Hg. The mean content of Cd and Zn were found to be 0.25 and 16.94 mg/kg f.w., respectively. In the case of Hg and As, these metals were detected at concentrations of 0.023 and 11.71 mg/kg f.w. The number of samples exhibiting results higher than the LOQ for Cd, As, Zn and Hg were found to be 24, 1, 50 and 1, respectively. The heavy metals content generally did not exceed the maximum permissible concentrations. Elevated content of Cd were detected in a single shrimp sample. The HI exceeded 1 among adults and children, with arsenic in shrimp identified as the predominant contributor. The ingestion of As from highest contaminated shrimp sample has been associated an elevated cancer risk among adult (2.33×10-3) and children (5.44×10-3). The findings of this study indicate that, in order to ensure the health safety of consumers, it is necessary to undertake more effective monitoring of the HMs content in seafood available in the Polish market.

As part of the Expert Panel of the Flavor and Extract Manufacturers Association's (FEMA) program to evaluate the safety of flavor ingredients, this publication, thirteenth in the series, details the re-evaluation of natural flavor complexes (NFCs) whose constituent profiles are characterized by mono- and sesquiterpene hydrocarbons. The Panel's constituent-based safety evaluation procedure parses the identified constituents of each NFC into well-defined congeneric groups. For each congeneric group, an evaluation based on the estimated intake is conducted using the conservative Threshold of Toxicological Concern (TTC) approach and a review of available data on absorption, metabolism and toxicity, including genotoxicity, for identified constituents and the NFCs, is conducted. The scope of the safety evaluation of the NFCs contained herein does not include added use in dietary supplements or any products other than food. Thirty-five NFCs, derived from the Angelica, Abies, Cananga, Croton, Apium, Canarium, Erigeron, Ferula, Zingiber, Humulus, Juniperus, Cistus, Commiphora, Boswellia, Piper, Pinus and Schinus genera were determined/affirmed as generally recognized as safe (GRAS) under their conditions of intended use as flavoring ingredients based on an evaluation of each NFC and the constituents and congeneric groups therein.

Immortalized cell lines function as invaluable tools in life science and preclinical studies. Poor laboratory practices can lead to cell line misidentification, cross-contamination, and mislabelling, resulting in invalid, misleading, and unrepeatable results. The issue of nonhuman-derived cell misidentification was once discovered timely, but it received less attention than the misidentification of human cells. Consequently, problematic murine cell lines still appear frequently in the literature. For instance, ImKC cells have been applied as a mouse Kupffer cell line in the last decade. In this report, we revealed that the ImKC cell line was a RAW 264.7 derivative through STR analysis, and further determined that it was not an SV40-transformed cell line by PCR and western blotting assays. Moreover, we outlined the relevant publications using the ImKC cell line. This study aims to prevent further researchers from employing the problematic cell line in their studies.

Acetaminophen (APAP) overdose is a leading cause of acute liver failure (ALF), with acute kidney injury (AKI) increasing morbidity and mortality. N-acetylcysteine (NAC) prevents APAP-induced liver damage, but not AKI, highlighting the need to address differential inter-organ responses to APAP toxicity. We investigated the relationship between hepatic glutathione (GSH) depletion, liver injury, and subsequent kidney damage following APAP overdose. Male C57BL/6J mice received either moderate (300 mg/kg) or severe (600 mg/kg) overdoses of APAP, with or without buthionine sulfoximine (BSO, 50 mg/kg) to deplete GSH, or NAC (500 mg/kg) to replenish GSH. A moderate APAP overdose elevated liver injury markers (alanine aminotransferase, ALT) without significantly affecting blood urea nitrogen (BUN) levels, though kidney injury molecule-1 (KIM-1) expression increased. A severe overdose significantly increased ALT activities, and BUN and creatine levels, together with marked upregulation of renal KIM-1 and histological evidence of cortical damage. BSO exacerbated APAP-induced kidney but not liver injury, where GSH remained depleted at 24 hours. In contrast, NAC protected against APAP hepatotoxicity but not AKI. Thus, these findings demonstrate critical organ-specific responses to APAP toxicity and underscore the need for targeted therapeutic strategies specifically addressing APAP-induced kidney injury.