Experimentally induced lipidosis in uterine and vaginal epithelium of rats.
The purpose of this study was to investigate the effects of two lipidosis-inducing drugs (the anorectic drug chlorphentermine and the tricyclic antidepressant-imipramine) upon the estrous cycle of rats and upon the morphology of the vaginal and uterine epithelia. After two weeks of continuous administration of high daily drug doses, the estrous cycle became stagnant. Ultrastructurally, the vaginal and uterine epithelia contained storage lysosomes which were filled with undigested polar lipids appearing as multilamellated material. The uterine luminal epithelium was most severely affected. The estrous cycle was abolished also by treatment with the anorexigenic drug phentermine, although this compound does not cause lipidosis. Therefore, the cessation of the estrous cycle cannot be attributed to the lipidosis as induced by chlorphentermine and imipramine; probably it is a consequence of the main actions of these psychotropic drugs. The biological basis for the exceedingly severe lipidosis in the uterine luminal epithelium is suggested to be the heavy load of polar lipids physiologically delivered to the lysosomal apparatus as long as the cycle-dependent apoptotic and autophagic processes were going on during the early period of drug treatment.
Geist
S H
SH
Department of Anatomy, University of Kiel, Germany.
Lüllmann-Rauch
R
R
D000818:Animals; D002745:Chlorphentermine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D004971:Estrus / Q000187:drug effects; D005260:Female; D007099:Imipramine / Q000633:toxicity; D008064:Lipidoses / Q000139:chemically induced / Q000473:pathology*; D008247:Lysosomes / Q000187:drug effects / Q000648:ultrastructure; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D014621:Vagina / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure
D002745:Chlorphentermine; D007099:Imipramine