Evaluation of brain and nerve pathology in rats chronically dosed with ddI or isoniazid
| Autor: | Larry C. Schmued, Annette Andrews, Jess Nickols, William Slikker, Jennifer A. Sandberg, Christopher M. Albertson |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Side effect Anti-HIV Agents Neurotoxins Antitubercular Agents Neural Conduction HIV Infections Neuropathology Pharmacology Toxicology Rats Sprague-Dawley Cellular and Molecular Neuroscience Developmental Neuroscience Reference Values Edema medicine Isoniazid Animals Humans Mast Cells Didanosine Myelin Sheath Myelinopathy business.industry Brain medicine.disease Sciatic Nerve Axons Rats Peripheral neuropathy Immunology Sciatic nerve medicine.symptom business medicine.drug |
| Zdroj: | Neurotoxicology and teratology. 18(5) |
| ISSN: | 0892-0362 |
| Popis: | The antiviral adenosine analog, 2',3'-dideoxyinosine (ddI), and the antitubercular nicotinic acid analogue, isoniazid, have recently received widespread clinical application in the treatment of acquired immunodeficiency syndrome (AIDS). Clinical studies indicate that the primary dose limiting side effect of both drugs is neurological in nature. Most clinical studies are confounded by the fact that the observed neuropathy must be evaluated in the presence of the ongoing disease process associated with human immunodeficiency virus (HIV) infection. The purpose of this study was to develop and validate a rat model of ddI-and isoniazid-induced neuropathy in the absence of any disease-induced pathology. Myelin splitting and intramyelin edema were the most frequent abnormalities observed in the sciatic nerves of ddI-dosed animals, whereas whorls, extracellular debris, macrophages, and reduced myelinated axon number were seen following chronic isoniazid administration. Isoniazid also resulted in myelinopathy of the CNS. Thus, contrary to previous reports, the rodent is a suitable model for ddI- and isoniazid-induced neuropathies. |
| Databáze: | OpenAIRE |
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