Comparative toxicities of amphotericin B and its monomethyl ester derivative on glial cells in culture
| العنوان: | Comparative toxicities of amphotericin B and its monomethyl ester derivative on glial cells in culture |
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| المؤلفون: | H M Geller, S P Racis, O J Plescia, Carl P. Schaffner |
| المصدر: | Antimicrobial Agents and Chemotherapy. 34:1360-1365 |
| بيانات النشر: | American Society for Microbiology, 1990. |
| سنة النشر: | 1990 |
| مصطلحات موضوعية: | Cell Membrane Permeability, Cell Survival, medicine.drug_class, Antifungal drug, Biology, Microbiology, Nephrotoxicity, In vivo, Amphotericin B, medicine, Animals, Pharmacology (medical), Cytotoxicity, Cells, Cultured, Myelin Sheath, Pharmacology, Neurotoxicity, medicine.disease, Rats, Infectious Diseases, Cell culture, Antiviral drug, Neuroglia, Cell Division, Research Article, medicine.drug |
| الوصف: | Amphotericin B (AmB) is a potent antifungal polyene macrolide antibiotic and is the drug of choice for the treatment of deep-seated mycotic infections. Its use is limited, owing to its nephrotoxicity, and it must be dispersed in deoxycholate for parenteral administration. In contrast, AME (the monomethyl derivative of AmB) is water dispersible, is appreciably less cytotoxic than AmB toward a variety of cell types, and is reportedly active against the acquired immunodeficiency syndrome virus (human immunodeficiency virus type 1). The latter activity has generated interest in AME as an antiviral drug. However, AME is perceived to be neurotoxic, based on the outcome of a human clinical trial of AME as an antifungal drug. AmB is not regarded as neurotoxic, presumably because any neurotoxicity in vivo is precluded by its nephrotoxicity. It was important, therefore, to determine the potential for neurotoxicity of the two agents in comparative tests, assessing the effects of their direct action against neural cells in culture. Rat cortical cells, comprising astrocytes and oligodendrocytes, were used. AME was at least 10 times less toxic than AmB and equally less toxic against several other nonneural cell types also included in these tests. Equally important, AmB disrupted the myelin sheath in these cultures, and it inhibited its generation. AME did not, even at a concentration 10 times greater than the toxic concentration of AmB. AmB is, therefore, potentially more neurotoxic than AME, contrary to current perception. AME is effective as an antifungal and antiviral drug at a concentration far below its toxic concentration for neural cells. Also, AME does not cross the blood-brain barrier appreciably, so that a therapeutic level in blood can be expected without encountering neurotoxicity. |
| تدمد: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.34.7.1360 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::07fa2053b97e35a3cdb772adce59669b https://doi.org/10.1128/aac.34.7.1360 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....07fa2053b97e35a3cdb772adce59669b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10986596 00664804 |
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| DOI: | 10.1128/aac.34.7.1360 |