Organ Growth Functions in Maturing Male Sprague-Dawley Rats

Abstract

Growth equations can be used in physiologically based pharmacokinetic (PBPK) modeling to provide physiological parameters (e.g., body weight, tissue/organ volumes) for maturing rodents. No diligent systematic exercise was found in the literature dealing with growth equations for developing rats' tissues. A generalized Michaelis–Menten (GMM) model, originally developed to fit body weight vs. age data, was chosen to estimate different physiological compartment sizes. The GMM model has the functional form: Wt = (Wt_o.K ^γ + Wt_max.Age ^γ )/ (K ^γ + Age ^γ ) where Wt is organ/tissue weight at a specified age, Wt_o and Wt_max are weight at birth and maximal growth respectively, and K and γ   are constants. Weights of freshly collected organs (liver, spleen, kidneys, heart, lungs, brain, gastrointestinal tract and adipose tissue), measured in male Sprague-Dawley rats of different ages (1–280 d) in our laboratory, were used to evaluate this model's performance. The GMM model was fitted to the organ weights, and the resulting parameters were statistically significant for all organs and tissues. Organ weights were highly correlated with their respective ages. GMM-derived organ growth and percent body weight (%BW) fractions of different tissues were plotted against animal age and compared with experimental values. The GMM-based organ growth and %BW fraction profiles were in general agreement with our empirical data as well as previous studies. The GMM model gave adequately precise weight predictions at all ages for all the tissues/organs examined.

This project was supported by U.S. EPA STAR grant R830800. The contents do not necessarily reflect the views and policies of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. Special thanks go to Srinivasa Muralidhara and Jerry Campbell for their help in the laboratory.