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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. SETAC North America, Minneapolis, MN, November 12 - 16, 2017.
Impact/Purpose:
This poster 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 can markedly reduce the extent to which hydrophobic organic chemicals accumulate in fish. However, predicting the impacts of biotransformation on chemical accumulation is complicated by a number of factors, including the possible influence of differences in fish size. In this study, liver S9 fractions from 4 sizes of rainbow trout (4 400 g) were used to evaluate the relationships between fish body weight and the content and activity of phase I and II metabolic enzymes. Phase I activity was assessed by measuring total cytochrome P450 (CYP) content, the activity of CYP1A toward 7-ethoxyresorufin (EROD), and the intrinsic clearance rates (CLIN VITRO,INT) of 3 polycyclic aromatic hydrocarbons (PAHs). Phase II activity was evaluated by measuring glucuronidation of p-nitrophenol by UDP-glucuronyltransferase (UGT) and the conjugation of 1-chloro-2,4-dinitrobenzene by glutathione S-transferase (GST). Regression analyses of log-transformed data, expressed on a gram of liver basis, revealed several allometric relationships. CYP content, UGT activity, and GST activity exhibited small but significant inverse relationships with fish body weight. In contrast, CLIN VITRO,INT rates for the 3 PAHs increased as body weight increased. However, weight normalized liver mass was also found to decrease inversely with fish body weight. When the data were recalculated on a gram of body weight basis, different patterns emerged. The inverse relationships between fish body weight and 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. Overall, metabolic activity varied by less than a factor of 3 across all sizes of fish. To our knowledge, this is the first investigation to systematically evaluate the relationships between fish body weight and metabolic activity of liver enzymes across a spectrum of substrates and reaction pathways. Results from this study may have important implications for in vitro to in vivo extrapolation of hepatic biotransformation data supporting chemical accumulation assessments for fish.