Effects of zuclomiphene in combination with triparanol and ay-9944 on developing rat CNS morphology and biochemistry

Developing rats were injected intraperitoneally twice weekly with a combination of three hypocholesterolemic agents: Zuclomiphene (formerly called trans-clomiphene; dosage, 30 mg/kg body weight), Triparanol (30 mg/kg body weight) and AY-9944 (3 mg/kg body weight). Treatment was initiated at 4 days of age. Biochemical and electron microscopic examination was conducted on animals sacrificed at 20 days of age. Cytoplasmic inclusion bodies were not seen in the CNS. Isolated edematous changes were seen in myelinated axons. Analysis of the sterol content of the brain and spinal cords of drug-treated animals indicated the presence of abnormal concentrations of five sterols, desmosterol, 5alpha-cholesta-7,24-dien-3beta-ol, zymosterol (5alpha-cholesta-8,24-dien-3beta-ol), 7-dehydrocholesterol (cholesta-5,7-dien-3beta-ol) and 7-dehydrodesmosterol (cholesta-5,7,24-trien-3beta-ol). Zymosterol and 5alpha-cholesta 7,24-dien-3beta-ol were minor constituents (5--7% and 1--1.5% of total sterol, respectively). The 7-dehydrosterols represented approximately one-half (44--52%) of the total CNS sterol.