title: Ro 15-1570, a new sulfur-containing retinoid devoid of bone toxicity in rats.
abstract: Repeated ingestion of high doses of retinoids cause the so-called hypervitaminosis A syndrome. In rats the main symptoms are weight loss, alopecia, erythema, desquamation of the skin, and alterations of the skeletal system, including bone fractures. In the present study, three retinoids (Ro 15-1570, arotinoid ethylsulfone, 6 mg/kg; retinoic acid, 100 mg/kg and etretinate, 50 mg/kg) were administered orally to rats for 1 and 2 weeks, respectively, to six male and six female rats/group. All the above changes were induced by all three retinoids, with the exception that the arotinoid ethylsulfone Ro 15-1570 did not cause bone alterations. The absence of toxic effects on the bones by Ro 15-1570 was confirmed by X-ray-film examinations, densitometry of the X-rayed femora and tibiae, examination of the thickness of the femoral and tibial compacta in histological slides plus the determination of the femoral ash weight and its main inorganic constituents (calcium, magnesium, sodium, and potassium). The present demonstration that the arotinoid ethylsulfone Ro 15-1570 was devoid of bone toxicity constitutes major progress in the pharmacologic development of retinoids with a better balance between therapeutic and adverse effects.
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000032:analysis / Q000187:drug effects*; D005050:Etretinate / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced; D005269:Femur / Q000032:analysis / Q000187:drug effects; D008297:Male; D051381:Rats; D012176:Retinoids / Q000633:toxicity*; D012867:Skin / Q000187:drug effects; D013977:Tibia / Q000187:drug effects; D013978:Tibial Fractures / Q000139:chemically induced; D014212:Tretinoin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D012176:Retinoids; D014212:Tretinoin; D005050:Etretinate; C045042:Ro 15-1570