Variability of blood biochemical parameters and establishing of reference ranges in nonclinical studies. Part 1: rats

N.G. Voitenko, M.N. Makarova, A.A. Zueva

Scientific-Production Organisation «Home of Pharmacy»

188663, Russia, Leningrad oblast, Vsevolozhskiy district, Kuzmolovskiy t.s., Zavodskaya st. 3-245

Е-mail:  [email protected]

Abstract

Establishing of current reference ranges for laboratory animal parameters is topical problem both in clinical and nonclinical studies. Retrospective analysis of 11 serum biochemical parameters in rats was conducted. Blood samples were collected from 195 male and 184 female rats (age 12–20 weeks and body weight 250–350 g.).

It was found that outliers of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were identified most frequent than other blood biochemical parameters in rats. This fact requiring increase in the number of repeatability in analyzing of blood parameters has to be taken into account when planning of study.

Reference ranges of data base including creatinine, urea, AST, ALT, alkaline phosphatase, cholesterol, triglycerides, total protein, albumin, glucose and total bilirubin and its’ inter-individual variance were identified. It was determined that alkaline phosphatase, triglycerides, glucose and total bilirubin have greatest inert-individual variance (more than 30%).

The data have been received from retrospective analysis was compared with reference interval of rat biochemical parameters from three large sources (Charles River, Taconic and Envigo). Reference intervals from literature sources also indicate high variance of some enzyme activity (including alkaline phosphatase), glucose, total bilirubin and triglycerides. Our calculated reference intervals was comparable with the same data from literature sources.

The results indicate that retrospective data analyzing allowing to access more accurate reference interval from larger data base without compromising ethical principles is preferable to use. Comparative analysis of inter-individual variance of rat and human blood biochemical parameters show the presence of species differences which need should be considered in discussion the preclinical study results.

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