RESUMEN
Numerous amphiphilic cationic drugs cause lipid-lysosomal storage in animal tissues; one of these drugs is amiodarone, a major antiarrhythmic agent. The toxicological effects of amiodarone were studied in three animal species (rats, dogs, and monkeys). It was shown that sublethal dose levels of amiodarone induced lipid storage in a great variety of tissues in rats (Fischer and Sprague-Dawley strains) and dogs. However, this change was not observed in baboons and Wistar rats. This storage, essentially characterized by lamellated inclusions, affected foamy macrophages, and at a later phase multiple cell types. Tissue biochemical analysis provided evidence of the phospholipidic nature of the storage. In addition, amiodarone induced an increased cholesterolemia and marked modifications of the lipoproteinogram. The kinetics of lipid storage was demonstrated following oral administration of amiodarone. After jejunal absorption, lipid storage occurred in the mesenteric lymph nodes followed by widespread deposition in the other lymph nodes and tissues, particularly in the lung. A complete recovery from lipid storage as observed in dogs and rats. Finally, an investigation of a correlation between animal and man by means of long-term experiments is proposed.
Asunto(s)
Amiodarona/toxicidad , Benzofuranos/toxicidad , Lipidosis/inducido químicamente , Animales , Colesterol/sangre , Perros , Células Espumosas/ultraestructura , Lipidosis/metabolismo , Lipidosis/patología , Pulmón/metabolismo , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Papio , Fosfolípidos/metabolismo , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas , Triglicéridos/sangreRESUMEN
Application of the deciduoma formation test showed that 3-benzofurol[3,2-c][1] benzoxepin-6(12H)-ylidene-N,N-dimethyl-l-propanamin-(E )-2-butenedioate (1:1) (oxetorone, L-6257, Nocertone) stimulated secretion of progesterone by the ovaries in rats and that this hyperprogesteronemia resulted from an increased secretion of prolactin. The studies carried out also showed that the apparition of uterine decidual lesions observed in certain animals undergoing chronic oxetorone treatment was linked to this hyperprogesteronemia. In view of the specific physiology of prolactin in rodents, such uterine lesions can only develop in these animals and cannot occur in man.
Asunto(s)
Benzoxepinas/farmacología , Decidua/efectos de los fármacos , Progesterona/sangre , Animales , Bromocriptina/farmacología , Castración , Femenino , Embarazo , Prolactina/sangre , Ratas , Ratas EndogámicasRESUMEN
When orally administered, 5-(3-diméthylamino propyliden)-benzofuro [2,3-c] benzoxepin-1, which antagonizes several biogenic amines, is slightly sedative and has also endocrinological properties in the Rat, induces the appearance of localized lesions of uterine stroma in 2 to 16% of the animals. The cytological picture could suggest a tumorogenesis. In fact, these lesions represent a non-tumoral reactional hyperplasia with nuclear abnormalities due to a hormonal stimulation.