Food and Chemical Toxicology最新文献

Chlorpyrifos (CPF), a widely used broad-spectrum organophosphate pesticide, has been associated with various adverse health effects in animals and humans. While its primary mechanism of action involves the irreversible inhibition of acetylcholinesterase, secondary mechanisms have also been suggested. The aim of the present study was to explore the secondary mechanisms of action involved in CPF-induced acute cytotoxicity using human hepatocarcinoma HepG2 cells. In particular, we investigated oxidative stress and mitochondrial function by assessing reactive oxygen species (ROS) generation, lipid peroxidation (LPO) and mitochondrial membrane potential (ΔΨ_m) alteration. Results showed that 24-h exposure to CPF (78.125–2500 μM) decreased cell viability in a concentration-dependent manner (IC₅₀ = 280.87 ± 26.63 μM). Sub-toxic CPF concentrations (17.5, 35 and 70 μM) induced increases in ROS generation (by 83%), mitochondrial superoxide (by 7.1%), LPO (by 11%), and decreased ΔΨ_m (by 20%). CPF also upregulated Nrf2 protein expression, indicating the role of the latter in modulating the cellular response to oxidative insults. Overall, our findings suggest that CPF caused hepatotoxicity through oxidative stress and mitochondrial dysfunction. Given the re-emerging use of CPF, this study emphasizes the need for comprehensive analysis to elucidate its toxicity on non-target organs and associated mechanisms.

Valproic acid (VPA), a common antiepileptic drug, can cause liver steatosis after long-term therapy. However, an impact of ferroptosis on VPA-induced liver steatosis has not been investigated. In the study, treatment with VPA promoted ferroptosis in the livers of mice by elevating ferrous iron (Fe²⁺) levels derived from the increased absorption by transferrin receptor 1 (TFR1) and the decreased storage by ferritin (FTH1 and FTL), disrupting the redox balance via reduced levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPX4), and augmenting acyl-CoA synthetase long-chain family member 4 (ACSL4) -mediated lipid peroxide generation, accompanied by enhanced liver steatosis. All the changes were significantly reversed by co-treatment with an iron-chelating agent, deferoxamine mesylate (DFO) and a ferroptosis inhibitor, ferrostatin-1 (Fer-1). Similarly, the increases in Fe²⁺, TFR1, and ACSL4 levels, as well as the decreases in GSH, GPX4, and ferroportin (FPN) levels, were detected in VPA-treated HepG2 cells. These changes were also attenuated after co-treatment with Fer-1. It demonstrates that ferroptosis promotes VPA-induced liver steatosis through iron overload, inhibition of the GSH-GPX4 axis, and upregulation of ACSL4. It offers a potential therapy targeting ferroptosis for patients with liver steatosis following VPA treatment.

Oral exposure to nanoparticles (NPs) may affect intestinal microbiota, and this effect may be further changed by co-contaminates. In the present study, we investigated the combined effects of TiO₂ NPs and fipronil (FPN) on microbiota in mouse intestines. Mice were intragastric exposed to 5.74 mg/kg TiO₂ NPs, 2.5 mg/kg FPN, or both of them, once a day, for 30 days. The results showed that individual exposure to TiO₂ NPs or FPN decreased body weight and induced pathological changes in intestines. The exposure was also associated with increased cleaved caspase-3 protein, oxidative stress and decreased tight junction protein expression. Furthermore, the levels of diamine oxidase (DAO), lipopolysaccharide (LPS) and inflammatory cytokines in serum were also elevated, indicating increased intestinal barrier permeability. As expected, both TiO₂ NPs and FPN decreased the diversity and altered the composition of microbiota. However, the observed effects were not further enhanced after the co-exposure to TiO₂ NPs and FPN, except that Romboutsia was only significantly increased after the co-exposure to TiO₂ NPs + FPN. We concluded that oral exposure to TiO₂ NPs and FPN showed minimal synergistic effects on microbiota in mouse intestine.

N-Methyl-N′-nitro-N-nitrosoguanidine (MNNG) and Helicobacter pylori might synergistically promote the malignant transformation of human esophageal epithelial cells (HEECs) through inducing DNA double-strand breaks (DSBs) and inhibition of PAXX protein expression. The long noncoding RNA (lncRNA) TUG1 is associated with multiple cancers, and its overexpression can promote cancer by interfering with the functions of oncogenes. LncRNA TUG1 is also associated with DNA methyltransferase 1 (DNMT1) and the epithelial signaling pathway of H. pylori infection. To explore the role of LncRNA TUG1 in the malignant transformation of HEECs induced by H.pylori + MNNG, a stable strain of HEECs with LncRNA TUG1 knockdown (LncRNA TUG1-KD) was constructed using RNA interference technology with lentivirus as a vector. Set up negative controls LncRNA TUG1-NC (null carrier lentivirus was selected to transfect HEECs) and block controls (normal HEECs without exposure). H. pylori + MNNG were added to the LncRNA TUG1-KD and LncRNA TUG1-NC groups for 6 h and then passaged until their malignant transformation. From each group, cells in the early, intermediate, and late stages of malignant transformation were used for the alkaline comet assay and determination of protein expression, including γ-H2AX and PAXX, by western blotting assay to assess DNA damage and repair processes. Clone formation assay in soft agar and nude mouse xenograft model was used to assess malignancy. This study suggests that H. pylori + MNNG promotes the malignant transformation of HEECs by inducing DNA DSBs and inhibiting PAXX expression, and this effect may be alleviated by LncRNA TUG1 knockdown. It elucidates the pathogenesis of EC from the perspective of the combined effect of epigenetic and environmental carcinogens, offering new insights for the comprehensive prevention and treatment of EC.

The presence of heavy metals in food products may seem an archaic concern; however, our study reveals that the risk is significant, unexpectedly in Food for Special Medical Purposes (FSMP) for oncology patients available in Polish pharmacies. This investigation fills that gap through a detailed toxicological analysis and health risk assessment of these heavy metals in FSMP products (n = 23) using inductively coupled plasma mass spectrometry (ICP-MS). Our comprehensive risk assessment involved evaluating (1) the concentrations of As, Cd, Hg, and Pb in both liquid and powdered FSMP formulations, (2) the amount of heavy metals ingested per serving as specified by the manufacturer, and (3) the cumulative daily and weekly intake adjusted for body weight, benchmarked against the provisional tolerable weekly intake (PTWI). While most samples were below PTWI limits, Cd levels raised concerns due to potential cumulative exposure risks, particularly for oncology patients consuming these products regularly. This study underscores the hidden dangers of heavy metal contamination in FSMP, emphasizing the need for vigilant monitoring and stringent regulatory frameworks to ensure patient safety. By uncovering these latent risks through meticulous toxicological assessment, our research provides crucial insights that could safeguard vulnerable populations. This study is significant due to concerns related to the complex risk assessment of FSMP for cancer patients, considering the complexity of oncological diseases and other comorbid factors, as well as the verification of available legal and regulatory acts of FSMP at the European Community level.

Idiopathic male infertility, a significant health concern, lacks a clear etiology. Cadmium (Cd), a widespread environmental pollutant known to impact male reproductive health negatively, can accumulate in mussels, a common food source in Egypt. This study investigated the link between ecological Cd exposure, oxidative stress, MT1A methylation, and idiopathic male infertility in two regions of Alexandria. Thirty-three infertile men and 33 fertile controls were included. Cd levels were measured in mussels from the study sites and in participants' blood and semen. Biomarkers reflecting Cd exposure and its effects were assessed. Mussel Cd levels exceeded regulatory limits. Infertile men revealed significantly higher blood and semen Cd levels, reduced semen quality, increased oxidative stress, and elevated MT1A methylation compared to controls. MT1A methylation was inversely correlated with sperm count and is the strongest predictor of idiopathic male infertility, demonstrating the lowest p-value and considerable effect size. This study suggests that environmental Cd exposure, potentially through mussel consumption, may contribute to idiopathic male infertility in Egypt by increasing oxidative stress, inducing epigenetic modifications, and impairing semen quality. These findings underscore the need for further research into the mechanisms underlying Cd-induced male infertility and the development of preventative strategies.

Grilled foods are an important source of acrylamide, which has neurotoxic, genotoxic, and carcinogenic properties. The current study aims to evaluate the level of acrylamide in beef, chicken, and fish products, especially those requiring high cooking temperatures, using High Performance Liquid Chromatography (HPLC). Reduction of acrylamide by organic acids i.e., (citric acid, malic acid, tartaric acid, and lactic acid) and fruit extracts of lemon, apple, and grape has also been investigated. The results revealed that the highest mean acrylamide concentration was found in chicken products (grilled chicken) which recorded 8.32 μg/100 g, followed by beef products (beef grilled) with a concentration of 7.91 μg/100 g, and fish products (pan-fried fish burgers) which recorded 6.77 μg/100 g). Furthermore, the mixture of organic acid has the highest effect on reducing the level of acrylamide in a chemical model system. Moreover, the fruit extract mixture was more effective in reducing the percentage of acrylamide in the grilled chicken than organic acids mixture. Finally, the addition of fruit extract improved the sensory properties of grilled chickens. In sum, this study offers novel and promising natural strategies to decrease acrylamide in meat products toward further future application in meat industry to deliver safe food to consumers.

Used in Southeast Asia for generations, kratom gained popularity in the United States and elsewhere over the past several decades. Derived from Mitragyna speciosa, kratom preparations including leaves, teas, powders, capsules, and extracts may yield stimulant, analgesic, and opioid-like effects that occur dose-dependently based on concentrations of kratom's key alkaloids, mitragynine and 7-hydroxymitragynine. Such effects are responsible for kratom's potential as a reduced-harm alternative to opiates and as a withdrawal treatment. But these properties are also associated with tolerance development and addictive potential. Given mitragynine and 7-hydroxymitragynine activity on cytochrome P450 isoforms and opioid receptors, adverse effects among polysubstance users are a concern. Current literature on the toxicology of kratom is reviewed, including product alkaloid concentrations, in vitro and in vivo data, epidemiological evidence, and human case data. The potential harms and benefits of kratom products are discussed within an exposure assessment framework, and recommendations for industry are presented. Current evidence indicates that kratom may have therapeutic potential in some persons and that products present few risks with typical, non-polysubstance use. However, few studies identified alkaloid doses at which adverse effects were expected in humans or animals. Such research is needed to inform future assessments of kratom's risks and benefits.

Cannabidiol (CBD) is the main component of plant Cannabis (Cannabis sativa), which exhibits strong antioxidant and anti-inflammatory activities. With the legalization of CBD in the United States, it is an inevitable tendency for its global legalization in the future. Therefore, it has become an urgent task to conduct the toxicological evaluation of CBD before clinical application. In this study, the developmental toxicities of CBD on zebrafish embryos were systematically evaluated, and the mechanisms were revealed. The results showed that the phenotype of liver degeneration was observed in 96 hpf zebrafish embryos after 0.1–5 μmol/L CBD exposure, further RT-qPCR experiments indicated that the above result may attributed by the alterations of FABP10A, GCLC, and GSR. Besides, 1 and 5 μmol/L CBD contributed to the developmental toxicities of heart and eye in zebrafish embryos, characterizing by the decrease in heart rate, the phenotype of pericardial edema, and the reduce of eye area. Compared to other organs, the liver of zebrafish displayed the most sensitive characteristic to CBD exposure, as 0.1 μmol/L CBD already led to the phenotype of liver degeneration. In summary, this paper provided theoretical supports for CBD toxicology research, and laid the foundation for its future clinical application.

Fenamiphos (FNP) is an organophospate pesticide that causes many potential toxicities in non-target organisms. Naringenin (NAR) has protective properties against oxidative stress. In this study, FNP (0.76 mg/kg bw) toxicity and the effect of NAR (50 mg/kg bw) on the liver and kidney of rats were investigated via biochemical, oxidative stress, immunohistochemical, cytopathological and histopathologically. As a result of biochemical studies, FNP caused oxidative stress in tissues with a change in total antioxidant/oxidant status. After treatment with FNP, hepatic and renal levels of AChE were significantly reduced while 8-OHdG and IL-17 levels, caspase-3 and TNF-α immunoreactivity increased compared to the control group. It also changed in serum biochemical markers such as ALT, AST, BUN, creatinine. Exposure to FNP significantly induced cytopathological, histopathological and immunohistochemical changes through tissue damage. NAR treatment restored biochemical parameters, renal/hepatic AChE, ultrastructural, histopathological and immunohistochemical changes modulated and blocked the increasing effect of FNP on tissues caspase-3 and TNF-α expressions, 8-OHdG and IL-17 levels. In electron microscopy studies, swelling was observed in the mitochondria of the cells in both tissues of the FNP-treated rats, while less ultrastructural changes in the FNP plus NAR-treated rats.