CHANGES IN RAT-HEART HISTOMORPHOMETRY DUE TO 2-WEEK DIETARY RESTRICTION

Citation
Je. Burkhardt et al., CHANGES IN RAT-HEART HISTOMORPHOMETRY DUE TO 2-WEEK DIETARY RESTRICTION, Toxicologic pathology, 24(5), 1996, pp. 636-638
Citations number
6
Categorie Soggetti
Toxicology,Pathology
Journal title
ISSN journal
01926233
Volume
24
Issue
5
Year of publication
1996
Pages
636 - 638
Database
ISI
SICI code
0192-6233(1996)24:5<636:CIRHDT>2.0.ZU;2-D
Abstract
In preclinical safety studies in which the administration of a test co mpound causes reductions in food consumption, body weights, and organ weights, it may be difficult to differentiate direct compound-induced effects on organ weights from those simply due to reduced nutrition. T o address this problem in reference to the heart, hearts were obtained from rats that were known to have had reductions in body weights and absolute heart weights as a result of feed restriction. Rats (40/sex) were divided into 4 groups (10/sex) and given quantities of ad libitum diet for 2 wk as follows: Group 1, 100%; Group 2, 75%; Group 3, 50%; and Group 4, 25%. Routine histologic evaluation was performed on longi tudinal sections of paraffin-embedded hearts stained with hematoxylin and eosin. Computer-assisted image analysis was conducted on left vent ricular free-wall of picrosirius red-stained sections for histomorphom etric evaluation of ratio of cross-sectional area occupied by myofiber s versus interstitium and for quantification of myofiber width. No dif ferences were detected histologically among groups, and no difference in the mean myofiber: interstitium ratio was detected between Groups 1 (9.1) and 4 (9.5). Mean values for myofiber width ranged from 24.6 mu m for Group 1 to 17.3 mu m for Group 4. Two-way ANOVA revealed a stro ng effect of dietary restriction on reduction of myofiber width but no consistent gender effect. The significant dietary effects occurred in Groups 3 and 4 compared to corresponding controls. The present author s speculate that, if reductions in feed intake were <50% in short-term preclinical studies, any reductions in myofiber width could imply a p rimary test article effect. Conversely, if reductions in feed intake w ere greater than or equal to 50% in such studies, reductions in myofib er width could be caused either solely by inadequate nutrition or by c ombined effects of nutrition and test article.