Food and Chemical Toxicology最新文献

This study presents a comprehensive multidimensional assessment of the safety and functional efficacy of Limosilactobacillus fermentum LF61, a strain isolated from human milk. Genomic analysis revealed no virulence factors (VFDB), drug resistance genes (CARD), or toxin synthesis gene cluster (antiSMASH) within its chromosome (2.04 Mb) and plasmid (15.5 kb), meeting EFSA's QPS safety criteria. In vitro studies demonstrated that LF61 exhibited a 2-hour survival rate of > 98% in gastric acid (pH 2.0) and a survival rate of 99.66% in intestinal fluid (pH 8.0). LF61 was also nontoxic to Caco-2 cells (metabolic activity at 20% concentration: 100.3 ± 2.1%). An acute oral toxicity test (in ICR mice) demonstrated an LD50 >2 × 10¹⁰ CFU/kg. In a randomized, double-blind clinical trial (n = 49), daily intake of 3×10¹⁰ CFU of LF61 for 8 weeks increased serum levels of the antimicrobial peptide LL-37 by 12.3% (p < 0.05), and IgA, IgG, and IgM by 18.7%, 15.2%, and 9.8%, respectively (p < 0.05). Metagenomic analysis revealed that LF61 promoted colonization by short-chain fatty acid-producing bacteria, such as Mitsuokella and Turicibacter (LDA > 3), activated the carbohydrate metabolism pathway (p = 0.002), and maintained stable α-diversity in the microbiome (Shannon index p > 0.05).Collectively, our findings indicate that LF61 exerts beneficial effects via a gut-immune axis bidirectional regulatory mechanism, offering a theoretical basis and clinical evidence for the development of novel immunomodulatory probiotics targeting the gut-immune axis.

Benzoic acid (BA) and acesulfame K (ACE) are commonly co-present food additives, yet their combined nephrotoxic risk remains poorly understood. Employing network toxicology, molecular simulations, and in vitro assays, we systematically evaluated their individual and combined effects on nephrotoxicity. Computational predictions indicated that both compounds exhibited nephrotoxic propensity, with shared targets enriched in pathways such as "response to xenobiotic stimulus" and metabolic disruption. Protein-protein interaction network analysis identified CTNNB1 and STAT3 as the respective core targets for BA and ACE, with molecular simulations confirming their stable binding. In vitro experiments showed that BA alone inhibited HK2 cell proliferation, and downregulated β-catenin (encoded by CTNNB1). ACE alone did not significantly suppress proliferation but activated STAT3 signaling. Notably, combined exposure produced a marked synergistic anti-proliferative effect, attributable to a dual mechanism: BA impaired renal tubular repair capacity by suppressing the CTNNB1/β-catenin pathway, while ACE exacerbated inflammatory and injury responses via STAT3 activation, thereby simultaneously impairing repair and exacerbating damage in the kidney. This study is the first to reveal that BA and ACE have the potential to synergistically induce nephrotoxicity via the CTNNB1/STAT3 signaling axis, providing new scientific evidence for the systematic safety assessment of mixed food-additive exposures.

Micro- and nanoplastics (MNPs) and fine particulate matter (PM2.5) have emerged as independent yet underrecognized environmental risk factors for cardiovascular disease (CVD). Their ultrafine size, large surface area, and high adsorptive capacity not only facilitate epithelial penetration and systemic translocation but also enable direct interactions with vascular and cardiac tissues. Growing epidemiological and experimental evidence links chronic exposure to MNPs and PM2.5 with endothelial dysfunction, atherogenesis, arrhythmogenesis, and myocardial injury. To ensure comprehensive coverage, we systematically searched PubMed, Web of Science, Embase, and Scopus for studies that investigated cardiovascular or metabolic effects of MNP and PM2.5 exposure. We synthesized available epidemiological and mechanistic evidence, focusing on the central role of oxidative stress, mitochondrial dysfunction, ferroptosis, immunometabolic reprogramming, endocrine disruption, and epigenetic remodeling in pollutant-induced cardiovascular pathology. These interrelated processes collectively impair endothelial function, promote atherosclerosis, and compromise cardiac integrity. This narrative review integrates emerging mechanistic insights, identifies potential early diagnostic biomarkers and therapeutic targets, and discusses prevention and policy strategies.

Arsenic is a prevalent environmental contaminant found in contaminated drinking water. However, the effects of arsenic exposure on the intestinal tract and the specific mechanisms of action remain unclear. In this study, we utilized subchronic sodium arsenite (NaAsO2)-exposed mice and the NaAsO2-treated human colon mucosal epithelial cell line 460 (NCM460) models to investigate the intestinal damage induced by arsenic. Hematoxylin-eosin (HE) staining revealed that the intestines of mice exposed to arsenic exhibited histological damage, characterized by the destruction of epithelial cells, a reduction in the thickness of the muscularis propria, and an increased infiltration of inflammatory cells within the colonic tissue. Mice exposed to arsenic demonstrated a significant reduction in the expression levels of the Occludin protein, accompanied by elevated concentrations of two biomarkers indicative of intestinal barrier damage: serum diamine oxidase (DAO) and lactate (D-LA). Analysis using 16S rRNA sequencing revealed that arsenic exposure did not significantly affect the α and β diversity of the mouse gut microbiota. However, it resulted in changes in the abundance of Clostridiaceae, Burkholderiaceae, Erysipelotrichaceae, and Helicobacteraceae increased, while Muribaculaceae decreased. Furthermore, exposure to arsenic led to increased protein levels of IL-1β, IL-6, and TNF-α, while simultaneously decreasing the expression of IL-10. Arsenic activated NF-κB signaling pathway, which involved in colonic inflammation. Finally, intervention with Pyrrolidine dithiocarbamate (PDTC) significantly attenuated arsenic-induced intestinal inflammation. In conclusion, arsenic exposure compromises the integrity of the intestinal mucosa and disrupts the homeostasis of the intestinal microbiota. Additionally, arsenic mediates intestinal inflammation through the NF-κB signaling pathway.

Dioxins and dioxin-like polychlorinated biphenyls (dl-PCBs) are persistent organic pollutants with known reproductive toxicity, particularly related to sperm quality. To explore the effects of dietary TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) exposure and the potential modulating influence of seafood nutrients, a 90-day feeding trial was conducted using prepubertal Wistar Han rats. The study used a 2 × 2 factorial design comparing diets based either solely on casein, or diets containing Atlantic salmon fillet as 50% of the protein source, with or without TCDD (200 ng/kg feed). The reproductive outcomes assessed were sperm count and plasma testosterone levels. Proteomic profiling of testis and hypothalamus was performed to provide further mechanistic insights. TCDD exposure resulted in significant accumulation in liver tissue but did not affect sperm count or testosterone levels. However, proteomic analysis revealed 247 differentially expressed proteins in testis tissue (FDR < 0.1), indicating effects on the redox balance, mitochondrial function, and cellular metabolism. No significant proteomic changes were observed in the hypothalamus, and no interactions between TCDD and the salmon-based diet were found with regards to molecular or reproductive endpoints. These findings suggest that moderate, subchronic dietary TCDD exposure induces subcellular stress responses in testis tissue without overt effects on sperm parameters in peripubertal rats. Inclusion of salmon fillet in the diet did not mitigate TCDD toxicity under these experimental conditions.

The long-term safety of genetically-modified (GM) crops, particularly their effects on cardiovascular health, remains a subject of scientific debate. This study systematically evaluated the effects of GM maize (Zea mays) feed on cardiovascular function in cynomolgus macaques (Macaca fascicularis) through two-generation feeding over 8 years. A comprehensive assessment of effects of the GM diet on myocardial injury, cardiac function, and arrhythmia risk was conducted using cardiac-specific biomarker assays, echocardiography, surface electrocardiography (ECG), and implantable cardiac monitoring. The F0 and F1 generations were included to explore the direct and potential transgenerational effects, respectively, of the GM diet. The results demonstrated no significant differences in either generation between the GM diet and control groups (normal feed and non-GM parental feed) in any of the markers assessed. These findings indicate that long-term feeding with GM maize-based diets does not significantly affect the cardiovascular function or increase the risk of arrhythmias in cynomolgus macaques.

Honey truffles (Mattirolomyces terfezioides) contain a natural protein which exhibits intense sweetness. This protein is produced via precision fermentation using Komagataella phaffii (formerly Pichia pastoris) as the chassis and is processed into a spray dried powder referred to as Honey Truffle Sweet Protein (HTSP) and the powder contains at least 50% w/w total protein, of which at least 50% is the active sweet protein, Honey Truffle Active Component (HT-AC). HT-AC is 1000-2000 times sweeter than sucrose dependent on food/beverage formulations. A set of genotoxicity assays and oral repeated dose studies were conducted to assess the safety of HTSP for its use as a sweetener in food and beverages. The results of the in vitro bacterial mutagenicity and mammalian cell micronucleus tests demonstrated a lack of genotoxic effects. In the 13-week oral exposure study, male and female Wistar Han rats were dosed by gavage to 1800, 3600, and 5400 mg/kg/day of HTSP (equivalent to approximately 500, 1000 and 1500 mg/kg/day of the HT-AC). Treatment was well tolerated with neither mortality nor HTSP-related adverse clinical pathology findings, organ weight effects, or macroscopic or microscopic observations. Consequently, the no observed adverse effect level (NOAEL) was 5400 mg/kg/day (1500 mg/kg/day HT-AC). The results supports the safety of HTSP for use as a dietary sweetener in food and beverage applications.

Perfluorohexanesulfonic acid (PFHxS), a prevalent short-chain per- and polyfluoroalkyl substance, has been implicated in hepatocellular carcinoma (HCC), but mechanisms remain unclear. We integrated transcriptomic analyses of The Cancer Genome Atlas (TCGA) liver cancer cohort and an HCC single-cell dataset with molecular docking and molecular dynamics simulations and in vitro assays to examine a PFHxS-relevant hypothesis involving KEAP1-NRF2 signaling. Across clinical datasets, higher NQO1, an NRF2-associated gene, was linked to adverse clinicopathologic features; NQO1-high tumor cells showed elevated NRF2-activity signatures and computationally inferred increased MIF signaling toward macrophages. Because exposure information is unavailable, these observations indicate association and define a PFHxS-relevant vulnerability axis rather than PFHxS-driven tumor states. Docking/dynamics suggested PFHxS can bind the KEAP1 Kelch domain near the NRF2-binding site. In HepG2 cells, PFHxS modestly increased viability/DNA-synthesis readouts and enhanced NRF2 nuclear localization, NQO1 protein abundance, and MIF secretion; pharmacologic NRF2 inhibition partially attenuated NRF2/NQO1 readouts and reduced MIF secretion. Together, the data support the hypothesis that PFHxS may engage a KEAP1-NRF2-related vulnerability axis, accompanied by NRF2/NQO1 pathway readouts and increased MIF secretion, motivating exposure-characterized and genetic studies to establish causality.