Dynamics of copper regulation in a marine clam Sinonovacula constricta at the organ level : Insight from a physiologically based pharmacokinetic model

Copper (Cu) is a common pollutant in estuaries and has received considerable attention worldwide. To gain an insight into the physiological mechanisms of waterborne Cu absorption, tissue distribution, storage, metabolism, and excretion in an estuarine razor clam Sinonovacula constricta, we developed a physiologically-based pharmacokinetic model based on prolonged Cu exposure with two exposure treatments. The tissues of S. constricta were divided into four parts: blood, digestive gland, gill, and other tissues. Our results showed that the waterborne Cu entered and exchanged with the gills and digestive gland, whereas digestive gland and other tissues were the main storage sites for Cu. Gills of S. constricta were able to maintain their Cu concentrations under both exposure treatments. Additionally, the gills exhibited a remarkable ability to remove Cu from water, with a transfer rate constant of 1.73 d⁻¹ from the gills to water, while restricting its transfer from the blood with a transfer rate constant of 0.0131 d⁻¹ from blood to gills. These results highlighted the crucial role of gills in regulating Cu levels in S. constricta as well as the detoxification and maintenance of metal homeostasis. Cu uptake rate constant in gill from waterborne was similar to that of digestive gland (0.294 vs. 0.364 L g⁻¹ d⁻¹), thus water entering the digestive tract was considered as another route of waterborne Cu absorption in bivalves. A significant amount of Cu in the blood was transferred to the digestive glands. These two factors explained the relatively higher Cu accumulation in the digestive glands than in other tissues in clams. The findings of this study enhanced our understanding of the homeostatic regulation and transportation mechanisms in marine bivalves. © 2023 Elsevier Ltd