Institute of Environmental Research at Greater Bay Area; Key Laboratory for Water Quality and Conservation of the Pearl River Delta, Ministry of Education, Guangzhou University, Guangzhou 510006, China.
Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Environ Sci Technol. 2020 Jun 16;54(12):7485-7493. doi: 10.1021/acs.est.0c01519. Epub 2020 May 22.
The 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 As(V) and biotransformation of As(V) in the marine medaka 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.
砷（As）的毒性针对生物体的特定组织，而鱼类组织间的砷生物转运仍知之甚少。本研究采用放射性示踪技术和基于生理的药代动力学（PBPK）模型，模拟了海洋马鲛鱼在水相暴露后 As(V)的生物转运（吸收、分布和消除）和 As(V)的生物转化。通过假设血液是不同隔室（鳃、肠、肝、头和胴体）之间的中间交换物，将鱼类模拟为一个六隔室模型。模型表明，肠和鳃是水相 As 的摄取、交换和消除部位，而胴体和头是主要的储存部位。肠在 As(V)的代谢中起着至关重要的作用，通过将无机 As 转化为砷甜菜碱（AsB），可能是由于肠道微生物群的重要作用。PBPK 模型常数与 As 形态（例如，AsB %、无机 As %和甲基化 As %）之间的相关性表明，AsB 倾向于储存在组织中而不是被排泄，而无机和甲基化 As 更容易从组织转移到血液中并被消除。首次将转化作用与模型模拟相结合，表明鱼类的肠是主要的代谢部位，而肠道微生物群介导的 AsB 合成有助于海洋鱼类的高砷生物累积。
