Development of a PBPK Model for Silver Accumulation in Chub Infected with Acanthocephalan Parasites

Abstract

Simultaneous presence of metals and parasites in fish might lead to potential risks to human health. Parasites might influence metal accumulation and disturb detoxification in fish, thereby affecting biomarkers of fish responses as well as metal biomagnification in humans. It is, therefore, of importance to take into account parasite infection when investigating metal accumulation in fish. However, mechanisms of metal accumulation and distribution in fish-parasite systems are not integrated into current approaches. The present study proposes a new physiologically-based pharmacokinetic (PBPK) model for mechanistic simulation of metal partitioning between intestinal parasites and their hosts. As a particular case, Ag accumulation in the system of chub Squalius cephalus and the acanthocephalan Pomphorhynchus tereticollis was investigated. As a novelty, fish cardiac output and organ-specific blood flow distribution were incorporated in our model. This approach distinguishes the current model from the ones developed previously. It also facilitates model extrapolation and application to varying conditions. In general, the model explained Ag accumulation in the system well, especially in chub gill, storage (including skin, muscle, and carcass), and liver. The highest concentration of Ag was found in the liver. The accumulation of Ag in the storage, liver, and gill compartments followed a similar pattern, i.e., increasing during the exposure and decreasing during the depuration. The model also generated this observed trend. However, the model had a weaker performance for simulating Ag accumulation in the intestine and the kidney. Silver accumulation in these organs was less evident with considerable variations.

Silver Diamine Fluoride in Children Using Physiologically Based PK Modeling

“…The purpose of our study was to predict exposure of silver following SDF application in children. A few PBPK models for ionic silver and silver nanoparticles have modeled silver absorption, tissue distribution, and excretion in fish, rats, and humans following exposure to silver from polluted environments, dietary supplements (e.g., colloidal silver or silver solutions), or nanoparticles (Lankveld et al 2010; Bachler et al 2013; Le et al 2018). Previous models did not provide values for all the physiological parameters or had different forms and routes of silver administration, rendering them unsuitable for extrapolation to children.…”

Approaching a closer surrogate for the biologically effective dose with subcellular partitioning-based toxicokinetic models

“…With the ability to accumulate various toxicants at high levels, several groups of parasites such as acanthocephalans have been considered potential sentinels (Sures et al, 2017). Consequently, parasites were further included in toxicokinetic models for predicting metal accumulation in fish-parasite systems (Le et al, 2014(Le et al, , 2018Le, Kiwitt, et al, 2022). By using sentinel organisms in biomonitoring, the bioavailable fraction that is the most able to exert effects on organisms is directly measured.…”

“…The development of multi-compartment models like physiologically-based toxicokinetic (PBTK) models (Gestin et al, 2021;Le et al, 2018;Le, Kiwitt, et al, 2022) allows for estimating tissue-specific metal concentrations. The concentration of pollutants in some tissues might be of limited toxicologically significance.…”

Modelling chronic toxicokinetics and toxicodynamics of copper in mussels considering ionoregulatory homeostasis and oxidative stress

“…The model was calibrated using data from Jorge et al (2013) using the MATLAB-based AMIGO toolbox as applied in our previous studies (Le et al, 2018(Le et al, , 2020. The parameters that describe NKA kinetics (k inact , k rec , M ATP2 , and k a3 ) were considered for calibration and simulation in the next step.…”