Modelling chronic toxicokinetics and toxicodynamics of copper in mussels considering ionoregulatory homeostasis and oxidative stress
Le, T.T Yen | Nachev, Milen | Grabner, Daniel | Garcia, Miriam R. | Balsa-Canto, Eva | Hendriks, A Jan | Peijnenburg, Willie J.G.M. | Sures, Bernd
Chronic toxicity of copper (Cu) at sublethal levels is associated with ionoregulatory disturbance and oxidative stress. These factors were considered in a toxicokinetic-toxicodynamic model in the present study. The ionoregulatory disturbance was evaluated by the activity of the Na⁺/K⁺-ATPase enzyme (NKA), while oxidative stress was presented by lipid peroxidation (LPO) and glutathione-S-transferase (GST) activity. NKA activity was related to the binding of Cu²⁺ and Na ⁺ to NKA. LPO and GST activity were linked with the simulated concentration of unbound Cu. The model was calibrated using previously reported data and empirical data generated when zebra mussels were exposed to Cu. The model clearly demonstrated that Cu might inhibit NKA activity by reducing the number of functional pump sites and the limited Cu-bound NKA turnover rate. An ordinary differential equation was used to describe the relationship between the simulated concentration of unbound Cu and LPO/GST activity. Although this method could not explain the fluctuations in these biomarkers during the experiment, the measurements were within the confidence interval of estimations. Model simulation consistently shows non-significant differences in LPO and GST activity at two exposure levels, similar to the empirical observation.
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