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Allometric scaling of hepatic biotransformation in rainbow trout.
Citation:
Fitzsimmons, P., A. Hoffman, K. Fay, AND J. Nichols. Allometric scaling of hepatic biotransformation in rainbow trout. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY - PART C: TOXICOLOGY & PHARMACOLOGY . Elsevier Science Ltd, New York, NY, 214:52-60, (2018). https://doi.org/10.1016/j.cbpc.2018.08.004
Impact/Purpose:
This manuscript presents results from experiments designed to investigate the relationships between hepatic biotransformation activity and fish body weight. Knowledge of chemical biotransformation is important to environmental toxicology research. Potential uses of this information is to support in vitro to in vivo or species to species extrapolations which can be used as inputs to chemical kinetic models to predict the impact of biotransformation on chemical accumulation in fish.
Description:
Biotransformation may substantially impact the toxicity and accumulation of xenobiotic chemicals in fish. However, this activity can vary substantially within and among species. In this study, liver S9 fractions from rainbow trout (4–400 g) were used to evaluate relationships between fish body mass and the activities of phase I and phase II metabolic enzymes. An analysis of log-transformed data expressed per gram of liver (g liver-1) showed that total cytochrome P450 (CYP) content, UDP-glucuronosyltransferase (UGT) activity, and glutathione S-transferase (GST) activity exhibited small but significant inverse relationships with fish body weight. In contrast, in vitro intrinsic clearance rates (CLIN VITRO,INT; mL min-1 mg protein-1) for 3 polycyclic aromatic hydrocarbons (PAHs) increased with increasing body weight. Weight normalized liver mass also decreased inversely with body weight, suggesting a need to express hepatic metabolism data per gram of body weight (g BW-1) in order to reflect the metabolic capabilities of the whole animal. When the data were recalculated in this manner, negative allometric relationships for CYP content, UGT activity, and GST activity became more pronounced, while CLIN VITRO,INT rates for the 3 PAHs showed no significant differences across fish sizes. Ethoxyresorufin O-deethylase (EROD) activity normalized to tissue weight (g liver-1) or body weight (g BW-1) exhibited a non-monotonic pattern with respect to body weight. The results of this study may have important implications for chemical modeling efforts with fish.
