Significance of zinc re-absorption in Zn dynamic regulation in marine fish revealed by pharmacokinetic model.

Zinc (Zn) is an essential but toxic trace element and is widely available in the natural environment. In the present study, we developed a re-absorption physiologically based pharmacokinetic (PBPK) model based on long-term dietary exposure to gain insights into the physiological mechanisms of uptake, tissue distribution, storage, and excretion of Zn in marine juvenile gilt-head breams Sparus aurata (with stomach). The PBPK model incorporated the kinetic processes of Zn transfer from fish liver to gastrointestinal system and used the Markov Monte Carlo algorithm to estimate the distribution of model parameters. The model fit indicated that the stomach and intestine of fish were key organs in regulating the concentration of Zn entering the internal environment, with excess exogenous Zn (120 mg/kg) being excreted in feces (rate constant of 5.23 d-1). Modeling results also indicated that liver (3.00 d-1), spleen (1.41 d-1) and kidney (0.51 d-1) were the main tissues responding to blood Zn flux by accumulation and detoxification. Fish kidneys exposed to 60 mg/kg and 120 mg/kg Zn had different regenerative capacities, resulting in different detoxification functions. A higher dietary Zn (120 mg/kg) disrupted the intestinal reabsorption process in marine fish. This study showed that exogenous Zn was directly accumulated in organs through the gastrointestinal-hepatic system, which is an important pathways for regulating metal homeostasis in marine fish. The results provided important understanding of the mechanisms of metal regulation and transport in marine fish.