Effects of Two Weeks of Feed Restriction on Some Common Toxicologic Parameters in Sprague-Dawley Rats

Author:

Levin Stuart1,Semler David1,Ruben Zadok2

Affiliation:

1. Searle R&D, Skokie, Illinois 60077

2. Hoffmann-LaRoche, Nutley, New Jersey 07110

Abstract

This study was intended to identify changes caused by short-term reduced feed intake in rats such as may occur with unpalatable feed or other forms of anorexia. For 2 wk, groups of rats (10/sex/group) were fed ad libitum (control group) or given 75% (mildly restricted group), 50% (moderately restricted group), or 25% (severely restricted group) of the amount of feed eaten the day before by controls. The control group and mildly restricted group grew steadily, but the terminal body weights of the mildly restricted group (both males and females) were only about 80% of controls. The moderately restricted group did not grow during the first week but grew slightly during the second week (terminal body weights about 65% of control). The severely restricted group lost weight throughout the study (terminal weight about 40% of control). Restricted groups exhibited hemoconcentration directly related to the degree of feed restriction. White blood cell counts were reduced (principally due to lymphopenia) in severely restricted rats. Platelet counts were decreased in all restricted groups. Total serum protein concentration was reduced (decreased globulins) in all female restricted groups and in the severely restricted males. The severely restricted rats had increased serum bilirubin, electrolyte derangements, and (in females only) decreased cholesterol. Thymus and liver weights (absolute and relative) were decreased in the moderately and severely restricted groups. All the feed-restricted groups had an increased incidence of superficial gastric erosions. The mildly and moderately restricted groups had slightly decreased hematopoietic tissue in sternal bone marrow, while the severely restricted group had bone marrow necrosis, thymic atrophy, and mild testicular degeneration. Findings in the severely restricted group were distinct from those in the other groups on the basis of their severity and were considered adverse. Changes in the mildly and moderately restricted groups were considered adaptive and innocuous since feed restriction of this degree has historically been associated with increased longevity and decreased disease incidence in chronic studies.

Publisher

SAGE Publications

Subject

Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine

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