Experimental neurotoxicity of the anorectic fenfluramine
Identifieur interne : 003532 ( Main/Exploration ); précédent : 003531; suivant : 003533Experimental neurotoxicity of the anorectic fenfluramine
Auteurs : D. K. Dastur [Inde] ; B. K. Thakkar [Inde] ; P. R. Desai [Inde]Source :
- Acta Neuropathologica [ 0001-6322 ] ; 1985-03-01.
English descriptors
- KwdEn :
- Teeft :
- Acta neuropathol, Amphophilic compound, Area postrema, Axon terminal, Bombay hospital, Brain weights, Cerebellar cortex, Cerebral neuron, Cerebrum, Chlorphentermine, Closer view, Control animals, Cytoplasm, Cytoplasmic inclusions, Dark cell, Dark cells, Dark neurons, Dastur, Dense bodies, Electron micrograph, Electron microscope study, Electron microscopes, Electron microscopy, Erwin riesch symposium, Experimental animal, Experimental animals, Fenfluramine, Fenfluramine hydrochloride, Fine structure, Glial cells, Golgi, Golgi complexes, Golgi tubules, Hydrophilic side chain, Hydrophobic benzene ring, Hypocholesterolemic drug, Inclusion, Intracytoplasmic inclusions, Lamellar, Lamellar bodies, Large number, Larger bodies, Largest number, Light microscopy, Lipid storage disorders, Lower border, Lysosomal, Lysosomal profiles, Microglia, Microglial cells, Mitotic division, Myelinated fibers, Nervous system, Neuron, Neuronal, Neuronal cytoplasm, Neuropil, Oligodendroglia, Osmiophilic, Osmiophilic debris, Perhexiline maleate, Raven press, Satiety center, Semithin sections, Similar lamellar inclusions, Spinal cord, Subependymal region, Such cells, Suzuki, Thin sections, Tissue breakdown, Tricyclic antidepressants, Ultrastructural study, Upper brain, Uranyl acetate, Various stages, Wallerian degeneration, White matter, Young animals, Young rats, Younger animals.
Abstract
Summary: Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic “reactive microglia” were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.
Url:
DOI: 10.1007/BF00688135
Affiliations:
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<term>Fenfluramine</term>
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<term>Largest number</term>
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<term>Lower border</term>
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<term>Lysosomal profiles</term>
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<term>Microglial cells</term>
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<term>Perhexiline maleate</term>
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<term>Semithin sections</term>
<term>Similar lamellar inclusions</term>
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<term>Subependymal region</term>
<term>Such cells</term>
<term>Suzuki</term>
<term>Thin sections</term>
<term>Tissue breakdown</term>
<term>Tricyclic antidepressants</term>
<term>Ultrastructural study</term>
<term>Upper brain</term>
<term>Uranyl acetate</term>
<term>Various stages</term>
<term>Wallerian degeneration</term>
<term>White matter</term>
<term>Young animals</term>
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<front><div type="abstract" xml:lang="en">Summary: Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic “reactive microglia” were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.</div>
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