Oral Excretion Kinetics of Food-Additive Silicon Dioxides and Their Effect on In Vivo Macrophage Activation.

A food additive, silicon dioxide (SiO2) is commonly used in the food industry as an anti-caking agent. The presence of nanoparticles (NPs) in commercial food-grade SiO2 has raised concerns regarding their potential toxicity related to nano size. While recent studies have demonstrated the oral absorption and tissue distribution of food-additive SiO2 particles, limited information is available about their excretion behaviors and potential impact on macrophage activation. In this study, the excretion kinetics of two differently manufactured (fumed and precipitated) SiO2 particles were evaluated following repeated oral administration to rats for 28 d. The excretion fate of their intact particles, decomposed forms, or ionic forms was investigated in feces and urine, respectively. Monocyte uptake, Kupffer cell activation, and cytokine release were assessed after the oral administration of SiO2 particles. Additionally, their intracellular fates were determined in Raw 264.7 cells. The results revealed that the majority of SiO2 particles were not absorbed but directly excreted via feces in intact particle forms. Only a small portion of SiO2 was eliminated via urine, predominantly in the form of bioconverted silicic acid and slightly decomposed ionic forms. SiO2 particles were mainly present in particle forms inside cells, followed by ionic and silicic acid forms, indicating their slow conversion into silicic acid after cellular uptake. No effects of the manufacturing method were observed on excretion and fates. Moreover, no in vivo monocyte uptake, Kupffer cell polarization, or cytokine release were induced by orally administered SiO2 particles. These finding contribute to understanding the oral toxicokinetics of food-additive SiO2 and provide valuable insights into its potential toxicity.

Urinary excretion kinetics of [177Lu]Lu-PSMA-617.

INTRODUCTION: For the implementation of suitable radiation safety measures in [177Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates this kinetics in prostate cancer patients via direct urine measurements. METHODS: Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples. Samples were measured on a scintillation counter to determine excretion kinetics. RESULTS: The mean excretion half-time during the first 20 h was 4.9 h. Kinetics was significantly different for patients with kidney function below or above eGFR 65 ml/min. Calculated skin equivalent dose in case of urinary contamination was between 50 and 145 mSv when it was caused between 0 and 8 h p.i.. Measurable amounts of 177Lu were found in urine samples up to 18 days p.i.. CONCLUSION: Excretion kinetics of [177Lu]Lu-PSMA-617 is especially relevant during the first 24 h, when accurate radiation safety measures are important to prevent skin contamination. Measures for accurate waste management are relevant up to 18 days.

Transfer and toxicokinetic modeling of non-dioxin-like polychlorinated biphenyls (ndl-PCBs) into accidentally exposed dairy cattle and their calves - A case report.

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that accumulate in tissues of exposed animals and humans. This case report refers ton=3 dairy cows accidentally exposed to non-dioxin-like PCBs (ndl-PCBs) of unknown origin on a German farm. At study start they had a cumulative total of 122-643 ng/g fat in milk and 105-591 ng/g fat in blood, consisting mainly of PCBs 138, 153, and 180. Two cows calved during the study and their calves were raised on their mothers' milk, resulting in cumulative exposure until slaughter. A physiologically based toxicokinetic model was developed to describe the fate of ndl-PCBs in the animals. The toxicokinetic behavior of ndl-PCBs was simulated in individual animals, including transfer of contaminants into calves via milk and placenta. Both the simulations and experimental data indicate that contamination via both routes is significant. In addition, the model was used to estimate kinetic parameters for risk assessment.

Fecal excretion kinetics provides further support for polyphenols targeting microbiota: An example with prebiotic-like phlorizin.

The microbiota plays important roles for polyphenols exerting bioactivity, which needs support to calculate the accumulated polyphenols in the gastrointestinal tract. Taking phlorizin as an example, fecal excretion kinetics was suggested to be ingenious for achieving it. No phlorizin was excreted with feces, implying almost 100 % total availability. Combined with its 0-5 % bioavailability, more than 95 % of phlorizin quantitatively accumulated in the gastrointestinal tract. Instead, trace phloretin was excreted, and the acquired kinetic parameters were influenced by physical conditions and dietary patterns. Dosage-total-availability curves indicated different relationships among normal-diet and obese mice, resulting in critical dosages of âˆ¼ 159 and âˆ¼ 196 mg/kg when taking 95 % total availability by phloretin. The dietary matrix affects the intake, digestion, metabolism and absorption of polyphenols, and may alter its total availability, and fecal excretion kinetics can provide further support for polyphenol dietary supplements targeting microbiota.

Urinary excretion of silibinin diastereoisomers and their conjugated metabolites in rat and human at different dosages.

Silibinin is a mixture of two flavonoid lignan silibinins A and B from the seeds of milk thistle (Silybum marianum L.). Using ultra-performance liquid chromatography/quadrupole time-of-flight-MS (UPLC/Q-TOF-MS), a total of 18 metabolites were identified in rat and human urine samples after oral administration of silibinin capsule. Furthermore, nine glucuronides and/or sulfated metabolites and two prototype compounds were simultaneously quantified in rat urine after oral administration of silibinin capsule at 50 and 100 mg/kg. Over a 72-h period, 27.6% and 23.3% of silibinin were excreted in the form of metabolites (n = 11) in urine, among which five major metabolites, including silibinin A-7-O-ß-glucuronide (SA-7G), silibinin B-7-O-ß-glucuronide (SB-7G), silibinin A-5-O-ß-glucuronide (SA-5G), silibinin B-5-O-ß-glucuronide (SB-5G) and silibinin A-20-O-glucuronide (SA-20G), accounted for 20.5% and 15.5% of the dosages, respectively, when administered at doses of 50 and 100 mg/kg. These results suggested that glucuronidation at the C7-, C5- and C20-hydroxyls was the primary metabolic pathway of silibinin diastereoisomers in vivo. The present results provide helpful information about the in vivo metabolism and clinical usage of silibinin capsule.

Earthworms' Degradable Bioplastic Diet of Polylactic Acid: Easy to Break Down and Slow to Excrete.

Microplastics (MPs) in soils may be ingested by terrestrial animals. While the application of bioplastics is increasing, the ingestion and excretion characteristics of bio-MPs by terrestrial animals are poorly understood as compared to fossil-MPs. Here, the approach-avoidance behavior of adult earthworms Eisenia fetida to MP-contaminated soil was assessed. Fossil-based poly(ethylene terephthalate) (PET) and bio-based poly(lactic acid) (PLA) MPs were found to be preferred by the earthworms, which might be due to the odor of polymer monomers. MPs in earthworm casts were analyzed by microscopy counting and liquid chromatography-tandem mass spectrometry. The amount of microscopically recognizable excreted PET and PLA was 553 and 261 items/g, respectively, while a higher proportion of smaller PLA particles also presented. Bio-based PLA is much easy to break down by earthworms than fossil-based PET. Submicron and nanocron PLA accounted for 57 and 13% of the excreted PLA on the 10th day of excretion. MP excretion was well described with the first-order kinetic model, and the elimination half-life was 9.3 (for PET) and 45 h (for PLA). A longer excretion period of PLA may be related to its potential to break down in the earthworms' digestive tract. This not only promotes the environmental degradation of PLA but also suggests the ecological risk caused by nanoparticles.

Excretion kinetics of three dominant organochlorine compounds in human milk within the first 6 months postpartum.

Breastfeeding is a specific and important way for women to eliminate harmful substances accumulated in body. Hexachlorobenzene (HCB), ß-hexachlorocyclohexane (ß-HCH), and 2,2-bis(p-chlorophenyl)-1,1-dichloroethene (p,p'-DDE) are dominant organochlorine compounds(OCCs) and persistent organic pollutants (POPs) accumulated in human being. Although a 6-month breastfeeding was suggested by the World Health Organization (WHO), the excretion characteristics of OCCs in human milk during the first 6-month lactation remain controversial. The main purpose of this study was to continuously monitor the three dominant OCC concentrations and reveal their elimination characteristic in human milk within the first 6-month lactation. To do that, with one sample per month, during their first 6-month lactation, human milk samples were continuously collected from 40 mothers after their first birth. The result showed that the concentrations of the three OCCs in human milk during the lactation continuously decreased from 51.7 to 39.9 µg/kg milk lipids for HCB, from 136.5 to 84.8 µg/kg milk lipids for ß-HCH, and from 307.3 to 192 µg/kg milk lipids, respectively. The excretion kinetics of each compound in milk lipids fitted zero-order kinetics during the 6-month lactation. The excretion rate of the three OCCs was approximately 3% per month for HCB and 7% per month for the other two compounds during the lactation, with tdec 1/2 of 13 months for HCB, 7.5 months for ß-HCH, and 8 months for p,p'-DDE. The excretion rate of the target compounds depended on initial deposited levels, compound properties, and exposure or input source.

The oral bioavailability, excretion and cytochrome P450 inhibition properties of epiberberine: an in vivo and in vitro evaluation.

Epiberberine (EPI) is a novel and potentially effective therapeutic and preventive agent for diabetes and cardiovascular disease. To evaluate its potential value for drug development, a specific, sensitive and robust high-performance liquid chromatography-tandem mass spectrometry assay for the determination of EPI in rat biological samples was established. This assay was used to study the pharmacokinetics, bioavailability and excretion of EPI in rats after oral administration. In addition, a cocktail method was used to compare the inhibition characteristics of EPI on cytochrome P450 (CYP450) isoforms in human liver microsomes (HLMs) and rat liver microsomes (RLMs). The results demonstrated that EPI was rapidly absorbed and metabolized after oral administration (10, 54 or 81 mg/kg) in rats, with Tmax of 0.37-0.42 h and T1/2 of 0.49-2.73 h. The Cmax and area under the curve values for EPI increased proportionally with the dose, and the oral absolute bioavailability was 14.46%. EPI was excreted mainly in bile and feces, and after its oral administration to rats, EPI was eliminated predominantly by the kidneys. A comparison of the current half-maximal inhibitory concentration and Ki values revealed that EPI demonstrated an obvious inhibitory effect on CYP2C9 and CYP2D6. Furthermore, its effect was stronger in HLM than in RLM, more likely to be a result of noncompetitive inhibition.

Studies on excretion kinetics of ten constituents in rat urine after oral administration of Shensong Yangxin Capsule by UPLC-MS/MS.

A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of 10 major active constituents in rat urine after oral administration of Shensong Yangxin Capsule (SSYX) using diazepam as an internal standard (IS). The urine samples were pretreated and extracted by solid-phase extraction prior to UPLC. Chromatographic separation was achieved on a Waters C18 (2.1 × 50 mm, 1.7 µm) column using a gradient elution program with 0.1% formic acid aqueous solution and acetonitrile at a flow rate of 0.4 mL/min. Detection and quantitation were accomplished by a hybrid quadrupole mass spectrometer using electrospray ionization source and multiple reaction monitoring in the positive ionization mode. The mass transition ion-pairs (m/z) for quantitation were all optimized and the total run time was 4.50 min. The specificity, linearity, accuracy, precision, recovery, matrix effect and stabilities were all validated for the analytes in urine samples. The validation results indicated that this method was simple, rapid, specific and reliable. The proposed method was successfully applied to investigate the urinary excretion kinetics of 10 compounds in rat after oral administration of SSYX.