Sex-specific reference intervals of hematologic and biochemical analytes in Sprague-Dawley rats using the nonparametric rank percentile method.

Qili He,Yong Jiang,Zhongren Jiang,Guoming Su,Huiping Xie,Jun Gao,Fangcheng Zhang,Lida Liu,Keliang Liu,Minwu Jin,Colin Johnson

doi:10.1371/journal.pone.0189837

Abstract

BackgroundHematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes. Reference intervals as presently defined for these analytes in Sprague-Dawley rats have not used internationally recommended statistical method nor stratified by sex. Thus, we aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline.MethodsHematology and biochemistry blood samples were collected from 500 healthy Sprague-Dawley rats (250 males and 250 females) in the control groups. We measured 24 hematologic analytes with the Sysmex XT-2100i analyzer, 9 biochemical analytes with the Olympus AU400 analyzer. We then determined statistically relevant sex partitions and calculated reference intervals, including corresponding 90% confidence intervals, using nonparametric rank percentile method.ResultsWe observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex. Males had higher hemoglobin, hematocrit, red blood cell count, red cell distribution width, mean corpuscular volume, mean corpuscular hemoglobin, white blood cell count, neutrophils, lymphocytes, monocytes, percentage of neutrophils, percentage of monocytes, alanine aminotransferase, aspartate aminotransferase, and triglycerides compared to females. Females had higher mean corpuscular hemoglobin concentration, plateletcrit, platelet count, eosinophils, percentage of lymphocytes, percentage of eosinophils, creatinine, glucose, total cholesterol and urea compared to males. Sex partition was required for most hematologic and biochemical analytes in Sprague-Dawley rats. We established sex-specific reference intervals, including corresponding 90% confidence intervals, for Sprague-Dawley rats.ConclusionsUnderstanding the significant discrepancies in hematologic and biochemical analytes between male and female Sprague-Dawley rats provides important insight into physiological effects in test rats. Establishment of locally sex-specific reference intervals allows a more precise evaluation of animal quality and experimental results of Sprague-Dawley rats in our toxicology safety assessment.

Highlights

Reference intervals are very important laboratory tools used to make a medical diagnosis, therapeutic management decision, or other physiological assessment in the clinical laboratory [1]
Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes
We observed that most hematologic and biochemical analytes of Sprague-Dawley rats were significantly influenced by sex

Summary

Introduction

Reference intervals are very important laboratory tools used to make a medical diagnosis, therapeutic management decision, or other physiological assessment in the clinical laboratory [1]. Hematologic and biochemical reference values are critical for assessing the health and disease states associated with the diagnosis of blood disorders, infectious diseases, immune system and lipoprotein metabolism, glucose regulation, and liver and kidney function When these parameters have deviated from their normal homeostatic state, the increase or decrease of their activities or concentrations could result in pathology [13]. Hematologic and biochemical analytes of Sprague-Dawley rats are commonly used to determine effects that were induced by treatment and to evaluate organ dysfunction in toxicological safety assessments, but reference intervals have not been well established for these analytes. We aimed to establish sex-specific reference intervals for hematologic and biochemical parameters in Sprague-Dawley rats according to Clinical and Laboratory Standards Institute C28-A3 and American Society for Veterinary Clinical Pathology guideline

Methods

Results

Conclusion