Food and Chemical Toxicology最新文献

Insight into symptoms at low doses of protein from priority allergenic foods may support decision making and acceptance of harmonized reference doses for Precautionary Allergen Labeling (PAL). Symptoms were extracted from double-blind placebo-controlled food challenges underlying the full range Eliciting Dose (ED) distributions (Houben et al., 2020). Frequency and severity were analyzed at and below doses to which a maximum 10% of the allergic population is predicted to respond with objective symptoms (ED10). Detailed symptom descriptions at every dose were recorded for 1102 food challenges with 11 allergenic foods. At doses ≤ED10, generally, 1 to 2 symptoms, either objective or subjective, occurred per positive challenge (average 1.8±1.2, range 1-8). Symptoms were mostly (68%) subjective of nature. Most objective symptoms were in the skin (60-71%; e.g. flush, erythema), followed by eyes/nose and oral cavity (rhinorrhea, red eyes, lip swelling). Far less symptoms (approx. 5-8%) occurred in the gastrointestinal (vomiting) and respiratory tract (cough). Symptoms were graded mild to moderate, except for 2 cases of a severe symptom (wheeze, laryngeal edema), which occurred at a dose above the ED05 (approximately the ED08). Exposure ≤ED05 of priority allergenic foods resulted only in mild to moderate symptoms in a small proportion of the allergic population.

This study aims to verify the effects of prolonged ingestion of coconut oil on the adrenal glands of Mongolian gerbils. Mongolian gerbils were used as an experimental model due to the morphological similarity of the adrenal glands to those of primates. Male Mongolian gerbils, 3 months of age, were divided into three experimental groups (n = 12): an intact control group, which received no treatment, a gavage control group, which received 0.1 ml of water daily by gavage, and a coconut oil-treated group, which received 0.1 ml of coconut oil daily for 12 months. The results showed that prolonged consumption of coconut oil caused an increase in cell area and thickness of the zona reticularis and the accumulation of lipid droplets, as well as reducing the amount of steroidogenic enzymes, such as CYP17, 3BHSD, and 17BHSD. It was also observed that the oil increased the expression of estrogen receptor alpha and their isoforms. These alterations allow us to conclude that changes in the lipid diet can cause alterations in the morphophysiology of the adrenal gland and, consequently, impact its functionality.

Objective: Recently, the pig liver model perfused ex vivo using a normothermic machine perfusion (NMP) has been proposed as a suitable model to study xenobiotic metabolism and biliary excretion. The aim of our study is to describe the metabolism of NPS such as cathinones (with a focus on 4-Cl-PVP and eutylone) in blood and bile, using a normothermic perfused pig liver model.

Methods: Livers (n = 4) from male large white pigs, 3-4 months of age and weighing approximately 75-80 kg, were harvested and reperfused onto an NMP (LiverAssist®, XVIVO) using autologous whole blood at 38 °C. 4-Cl-PVP and eutylone were administered as a bolus in the circulating blood at T0 with the aim of achieving a concentration of 1 μg/mL in the reperfusion system. The assays were carried out on plasma and bile between 0 and 120 min after cathinone administration using an targeted and untargeted approaches based on liquid chromatography coupled with high resolution mass spectrometry (Q-Exactive Thermo Scientific®).

Results: In plasma, the concentration of 4-Cl-PVP and eutylone decreased rapidly with elimination half-lives of 4 min and 0.25 min, respectively. Their phase I and phase II metabolites were detected in plasma as early as 1 min. In bile, 4-Cl-PVP and eutylone were detected with maximum intensity between 0 and 30 min post-administration, and the main metabolites found in plasma were found in bile. Phase II derivatives showed increasing biliary excretion over time up to 120 min.

Conclusion: The pig liver model perfused ex vivo using an NMP represent a promising model in pharmaco-toxicology, particularly for toxicokinetic investigations of cathinones. This model may be of interest in the absence of authentic cases of cathinone consumption or other NPS consumption to identify relevant metabolites consumption markers. In addition, the possibility of collecting bile in this model represents an additional advantage for studying biliary excretion of NPS and their metabolites in forensic toxicology.

Environmental stressors, such as air particulate matter (PM) and nutrient deficiencies, can significantly impact crucial organs involved in detoxifying xenobiotics, including lungs, liver, and kidneys, especially in vulnerable populations like children. This study investigated the effect of 4-week exposure to Residual Oil Fly Ash (ROFA) on these organs in young rats under growth-restricted nutrition (NGR). We assessed histological, histomorphometric and biochemical parameters. ROFA exposure induced histological changes and inflammation in all three organs when compared to control (C) animals. Specifically, in lungs ROFA caused a significant reduction in alveolar airspace (C: 55.8±1.8% vs. ROFA: 38.7±3.0%, p<0.01) and alveolar number along with changes in alveolar size distribution, and disruption of the smooth muscle layer which may impaired respiratory function. In the liver, ROFA increased: binucleated cells, macro and microvesicles and both AST and ALT serum biomarkers (AST: C=77.7±1.3 vs. ROFA=81.6±1.3, p<0.05; ALT: C=44.5±0.9 vs. ROFA=49.4±1.3, p<0.05). In the kidneys, a reduced Bowman's space (C: 2.15±0.2 mm² vs. ROFA: 1.74±0.2 mm², p<0.05) was observed, indicative of glomerular filtration failure. NGR alone reduced Bowman's space (C: 2.15±0.2 mm² vs. NGR: 1.06±0.1 mm², p<0.001). In lung and liver NGR showed higher levels of proinflammatory cytokine IL-6 (p<0.01 and p<0.001, respectively) when compared to C. In conclusion, both stressors negatively affected lung and excretory organs in young rats, with nutritional status further modulating the physiological response to ROFA. These findings highlight the compounded risks posed by environmental pollutants and poor nutrition in vulnerable populations.

Hop extracts containing prenylated polyphenols such as 8-prenylnaringenin (8-PN) and its precursor isoxanthohumol (iXN) are popular among women seeking natural alternatives to hormone therapy for postmenopausal symptoms. Due to structural similarities with estrogens, these compounds act as estrogen receptor agonists. Especially 8-PN, described as the most potent phytoestrogen known to date, poses a potential risk for endocrine disruption. Therefore, its use as a hormone replacement raises concerns for human health. However, a significant challenge in assessing the potential endocrine-disruptive effects of hop polyphenols is the lack of data on their toxicokinetics. Particularly, information on in vivo concentrations in target tissues is lacking. To address this gap, we developed a physiologically based kinetic (PBK) model tailored to female physiology. The model was used to predict the levels of hop polyphenols in human blood and target tissues under realistic exposure scenarios. The predictions suggest that iXN and 8-PN concentrations in target tissues reach the low nanomolar range after dietary supplementation. This study enhances our understanding of internal concentrations of iXN and 8-PN after dietary consumption and is of direct applicability for respective risk assessment.

Eugenol has pharmacological properties, but its impact on renal function is limitedly studied. Thus, this study evaluated the effects of eugenol at 10, 20, and 40 mg kg^-1, administered via gavage for 60 days, on histological, biochemical, oxidative, and proteomic parameters in rat kidneys. Adult Wistar rats treated with 10 mg kg^-1 of eugenol had kidneys with low total antioxidant capacity, high nitric oxide content, and high percentual of blood vessels, with no damage to renal function or morphology. The kidney proteome revealed an upregulation of proteins associated with energy metabolism, oxidative stress, and mitochondrial function. Eugenol at 20 mg kg^-1 did not alter kidney histology but inhibited Na⁺/K⁺ ATPase activity. This dose elicited an upregulation of proteins associated with mitochondrial function and cellular defense. Finally, 40 mg kg^-1 eugenol had more pronounced effects on the kidney, increasing serum sodium, potassium, and chloride levels, inhibiting Na⁺/K⁺ ATPase activity, triggering an adaptive response to oxidative stress, and showing apical brush border thinness in proximal tubules. We concluded that eugenol exerted dose-dependent effects on kidney function and morphology. These findings highlight the importance of careful consideration of eugenol's dosage in therapeutic applications.

Flame retardant polybrominated diphenyl ethers (PBDEs) accumulate in human bodies through food and dust ingestion, and cause neurobehavioral deficits with obscure mechanism. We aimed to investigate NMDAR-CaMKⅡγ-mediated synapse-to-nuclear communication involved in BDE-209-induced cognitive impairment, and alleviation from exogenous melatonin. Decreased NMDAR subunits GluN2A and 2B, autophosphorylation of CaMKⅡα, and postsynaptic GluA1 trafficking were observed in the hippocampus of juvenile rats after maternal BDE-209 exposure. Moreover, nuclear shuttling of CaMKⅡγ with CaM, as well as downstream nuclear p-CaMKIV and p-CREB-dependent genes (Bdnf, c-Fos, Arc) expression were all causally down-regulated. These resulted in less dendritic spines in CA1 area and poor spatial learning and memory. Importantly, elevated miR-219a-5p in transcriptome sequencing was identified together with its targets Grin2b and Camk2g mRNA, further elucidated the reduction in GluN2B and CaMKⅡγ protein. These changes on synaptic plasticity caused by BDE-209 were reversed correspondingly under pretreatment of melatonin, partially via miR-219a inhibition. Collectively, our findings suggest that synaptonuclear signaling alterations potentially mediated neurobehavioral deficits induced by early-life BDE-209 exposure and the neuroprotection from melatonin, therefore provided a novel perspective for prevention.