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Physiologically Based Pharmacokinetic Model for the Biotransportation of Arsenic in Marine Medaka (Oryzias melastigma)
journal contribution
posted on 2020-05-22, 19:44 authored by Wei Zhang, Dongdong Song, Qiao-Guo Tan, Wen-Xiong Wang, Li ZhangThe toxicity of arsenic (As) targets
specific tissues of organisms,
while the biotransportation of As among the tissues of fish remains
poorly understood. In the present study, radiotracer techniques followed
by a physiologically based pharmacokinetic (PBPK) modeling were applied
to simulate the biotransportation (absorption, distribution, and elimination)
of 73As(V) and biotransformation of As(V) in the marine
medaka Oryzias melastigma after waterborne
As exposure. Fish were simulated by a six-compartment model by assuming
that blood was the intermediate exchange among different compartments
(gill, intestine, liver, head, and carcass). Modeling suggested that
intestine and gill were the uptake, exchange, as well as elimination
sites of waterborne As, while carcass and head were the main storage
sites. Intestine played a vital role in the metabolism of As(V) by
biotransforming inorganic As into arsenobetaine (AsB), possibly because
of the important role of gut microbiota. The correlation between the
PBPK model constants and the As speciation (e.g., AsB %, inorganic
As %, and methylated As %) indicated that AsB tended to be stored
in the tissues rather than being depurated, while inorganic and methylated
As were more easily transferred from tissues to the blood and eliminated.
Modeling simulation coupling with biotransformation for the first
time demonstrated that the fish intestine was the main metabolic site,
and synthesis of AsB as mediated by the microbiota in the intestine
contributed to the high As bioaccumulation in marine fish.
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tissueMarine MedakaAsBgut microbiotaPharmacokinetic Modelsix-compartment modelmethylatedrolePBPK model constantsstorage sitesmarine medaka Oryzias melastigmamodeling simulationcarcassgillwaterbornefish intestinemarine fishOryzias melastigmaradiotracer techniqueselimination sitesbiotransformationbiotransportation
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