Food and Chemical Toxicology最新文献

Prevention of anticancer drugs-induced cardiotoxicity remains an imperative area of oncology research as it continues to be a major challenge in cancer chemotherapy. This study was undertaken to investigate the protective effect of methanol extract of Morchella esculenta (ME) against cyclophosphamide (CP)-induced cardiotoxicity. Myocardial damage was assessed by biochemical and histopathological methods. Proinflammatory cytokines gene expression was determined by RT-PCR analysis. To assess the mitochondrial dysfunction, TCA cycle and electron transport chain complexes enzymes activities were determined. Chemical finger print of ME was accomplished by HPTLC. CP (200 mg/kg) treated animals showed elevation in cardiac injury markers which was attenuated by ME (p<0.05). CP-induced decline of antioxidant status and expression of nuclear factor erythroid 2-related factor 2 were restored by ME. CP-induced expression of NF-ĸB, IL1-β, IL-6, TNF-α, COX-2 and iNOS (p<0.05) was attenuated by ME (500 mg/kg). Bioactive compounds namely, 5-eicosapentaenoicacid (C20H30O2), 8-hydroxyoctadecadienoic acid (C18H32O3), 4,4-dipo-zetacarotene (C30H44), CynarosideA ( C21H32O10) present in the extract might be responsible for cardioprotection. The findings reveal the protective effect of ME against CP-induced cardiomyopathy.

2,4-dinitroaniline (2,4-D), a widely used dye intermediate, is one of the typical pollutants, and its potential health risks and toxicity are still largely unknown. To explore its subchronic oral toxicity, Wistar rats (equal numbers of males and females) were used as test animals, and a 90-day oral dosing experiment was conducted, divided into control group, low-dose group (0.055 mg/kg), medium-dose group (0.22 mg/kg), medium-high dose group (0.89 mg/kg), and high-dose group (3.56 mg/kg). The body weight data, clinical appearance, and drug reactions of each test rat within 90 days of dosing were recorded; morning urine samples were collected four times to test for eight urinary indicators; blood samples were collected to test for nineteen hematological indicators and sixteen biochemical indicators; tissue samples were collected for pathological analysis; moreover, the no-observed-adverse-effect level (NOAEL) was determined, and the benchmark dose method was used to support this determination and provide a statistical estimate of the dose corresponding. The results indicated that the chronic toxicity of 2,4-dinitroaniline showed certain gender differences, with the eyes, liver, and kidneys being the main potential target organs of toxicity. Moreover, the subchronic oral NOAEL for 2,4-dinitroaniline was determined to be 0.22 mg/kg body weight (0.22 mg/kg for males and 0.89 mg/kg for females), and a preliminary calculation of the safe exposure limit for human was 0.136 mg/kg. The research results greatly enriched the safety evaluation data of 2,4-dinitroaniline, contributing to a robust scientific foundation for the development of informed safety regulations and public health precautions.

Pb toxicity is linked to cardiovascular and nephrotoxicity issues. Exposure to this heavy metal can occur through food and drinking water. Therefore, this study aimed to evaluate Pb exposure and assess health risks in Korean adults using a physiologically based toxicokinetic (PBTK) model. Human blood Pb concentrations were monitored using the Korean National Environmental Health Survey (KoNEHS) Cycle 4. The average Pb exposure in Korean adults was 0.520 μg/kg bw/day. The PBTK results were compared with scenario-based results from the 2021 risk assessment report of five heavy metals, including Pb, conducted by the MFDS. Exposure determined through reverse dosimetry was approximately two times higher than scenario-based exposure (0.264 μg/kg bw/day). The higher exposure levels obtained during PBTK analysis may be attributed to sustained exposure within historically more contaminated living environments and the long half-life of Pb. These findings suggest that the PBTK-based method can quantify aggregated exposure levels in the body over time, potentially serving as a complementary tool to address the constraints of scenario-based assessment methods for integrated risk assessment. Moreover, this model is convenient and cost-effective compared with scenario-based exposure estimation. These findings can facilitate the application of model for tracking continuous national changes in hazardous substance levels.

Real-life pollution usually involves simultaneous co-exposure to different chemicals. Metals and drugs are frequently and abundantly released into the environment, where they interact and bioaccumulate. Few studies analyze potential interactions between metals and pharmaceuticals in these mixtures, although their joint effects cannot be inferred from their individual properties. We have previously demonstrated that the mixture (PC) of the metals Cd and Hg, the metalloid As and the pharmaceuticals diclofenac (DCF) and flumequine (FLQ) impairs hepatic proteostasis. To gain a deeper vision of how PC affects mouse liver homeostasis, we evaluated here the effects of PC exposure upon some biochemical and morphometric parameters, and on the transcriptional profiles of selected group of genes. We found that exposure to PC caused oxidative damage that exceeded the antioxidant capacity of cells. The excessive oxidative stress response resulted in an overabundance of reducing equivalents, which hindered the metabolism and transport of metabolites, including cholesterol and bile acids, between organs. These processes have been linked to metabolic and inflammatory disorders, cancer, and neurodegenerative diseases. Therefore, our findings suggest that unintended exposure to mixtures of environmental pollutants may underlie the etiology of many human diseases. Fortunately, we also found that a diet enriched with selenium mitigated the harmful effects of this combination of toxicants.

Alicyclobacillus bacteria are important contaminants in the beverage industry because their spores remain in the product after usual pasteurization. At the same time, their impact on human health has yet to be characterized, as it is generally assumed to be low or non-existent. However, these bacteria are causing quality concerns mainly due to odor and taste changes of the product. Since potential health effects are not precisely known, an experimental assessment was performed, including a biosafety assessment of six viable and non-viable vegetative and spore forms of Alicyclobacillus spp. strains using cell cultures and rodent study. The monolayer of Caco-2 (Cancer coli-2) cells was investigated for its adsorption effect on the epithelium of the small intestine of mice. Lactate dehydrogenase leakage (LDH) and transepithelial electrical resistance (TEER) tests were used to ensure the integrity of the cell membrane and tight junctions. The methylthiazole tetrazolium bromide (MTT) assay examined in vitro cytotoxicity in Caco-2 and HepG2 cell lines. The hemolysis of erythrocytes was spectrophotometrically measured. The results showed negligible cytotoxicity or non-toxic response in mice. In conclusion, Alicyclobacillus spp. exhibited biocompatibility with negligible cytotoxicity and minimal safety concerns.

Nanosilver (AgNPs) is popular nanomaterials used in food industry that makes gastrointestinal tract an essential route of its uptake. The aim of the presented study was to assess the effects of intragastric exposure to AgNPs on redox balance and steroid receptors in the testes of adult Fisher 344 rats. The animals were exposed to 20 nm AgNPs (30 mg/kg bw/day, by gavage) for 7 and 28 days compared to saline (control groups). It was demonstrated that 7-day AgNPs administration resulted in increased level of total antioxidant status (TAS), glutathione reductase (GR) activity, lower superoxide dismutase activity (SOD), decreased glutathione (GSH) level and GSH/GSSG ratio, as well as higher estrogen receptor (ESR2) and aromatase (Aro) protein expression in Leydig cells compared to the 28-day AgNPs esposure. The longer-time effects of AgNPs exposition were associated with increased lipid hydroperoxidation (LOOHs) and decreased SOD activity and androgen receptor protein level. In conclusion, the present study demonstrated the adverse gastrointestinally-mediated AgNPs effects in male gonads. In particular, the short-term AgNPs exposure impaired antioxidant defence with concurrent effects on the stimulation of estrogen signaling, while the sub-chronic AgNPs exposition revealed the increased testicle oxidative stress that attenuated androgens signaling.

The human gut microbiome plays a crucial role in immune function. The synbiotic consortium or Defined Microbial Assemblage™ (DMA™) Medical Food product, SBD121, consisting of probiotic microbes and prebiotic fibers was designed for the clinical dietary management of rheumatoid arthritis. A 28-day repeated administration study was performed to evaluate the oral toxicity of SBD121 in male and female rats (age/weight at study start: 60 days/ 156-264 grams) administered levels of 0, 4.96 x 10¹⁰, 2.48 x 10¹¹, or 4.96 x 10¹¹ colony forming units (CFU)/kg-bw. No treatment related changes in ophthalmological effects, mortality, morbidity, general health and clinical observations, urinalysis, hematology, serum chemistry, absolute or relative organ weights, gross necropsy, or histopathology. A significant decrease in body weight was reported in females in the low and high-concentration groups, which corresponded in part with a significant decrease in food consumption. Results of the functional observation battery indicated front grip strength was significantly greater in the high-concentration males compared to the controls; however, this effect was not considered adverse. Based on these findings, the administration of the Medical Food SBD121 to male and female rats has a no-observable adverse effect level (NOAEL) at the highest level tested of 4.96 x 10¹¹ CFU/kg-bw.