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Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats

Itraconazole and Fluconazole are the newer antifungal drugs that have been used for several years. Both these drugs have a broad-spectrum antifungal activity and currently are used to treat infections caused by Candida albicans, Aspergillus spp., Paracoccidioides brasiliensis, Sporothrix schencki...

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Main Author: Abdul Rahman, Nor Shahida
Format: Thesis
Language:English
English
Published: 2004
Online Access:http://psasir.upm.edu.my/id/eprint/6296/1/FPSK%28M%29_2004_8.pdf
http://psasir.upm.edu.my/id/eprint/6296/
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spelling my.upm.eprints.62962023-10-20T08:50:10Z http://psasir.upm.edu.my/id/eprint/6296/ Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats Abdul Rahman, Nor Shahida Itraconazole and Fluconazole are the newer antifungal drugs that have been used for several years. Both these drugs have a broad-spectrum antifungal activity and currently are used to treat infections caused by Candida albicans, Aspergillus spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Ciyptococcus neoformans and many others. The objective of this study is to investigate the in vitro and in vivo cytotoxicity of these two antifungal drugs. The in vitro and in vivo cytotoxicity of fluconazole and itraconazole were studied in thirty eight male Sprague Dawley rats. Freshly isolated rat hepatocytes were obtained for the in vitro treatment of fluconazole and itraconazole using a liver perfusion technique. The cell viability test was done by trypan blue exclusion. As a result, both fluconazole and itraconazole cause a reduction in cell viability of hepatocytes. However, itraconazole exerted its cytotoxicity more than fluconazole in both time- and dosedependent manner. Meanwhile, cytotoxicity of itraconazole was reduced significantly by Phenobarbital pretreatment. Phenobarbital did not have any effect on the .-. i l l cytotoxicity induced by fluconazole. In vivo studies revealed that rat's liver and kidney treated with repeated-doses of itraconazole showed a significantly higher in total protein in liver and kidney and significant increase in serum ALP and ALT activity. This is in agreement with histological findings that the rat treated with repeateddoses of itraconazole showed severe histological features compared to fluconazole. Morphological changes such as inflammation and fibrosis of liver were frequently seen in repeated-doses of itraconazole. This present study suggests that Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro. 2004-03 Thesis NonPeerReviewed text en http://psasir.upm.edu.my/id/eprint/6296/1/FPSK%28M%29_2004_8.pdf Abdul Rahman, Nor Shahida (2004) Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats. Masters thesis, Universiti Putra Malaysia. English
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
English
description Itraconazole and Fluconazole are the newer antifungal drugs that have been used for several years. Both these drugs have a broad-spectrum antifungal activity and currently are used to treat infections caused by Candida albicans, Aspergillus spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Histoplasma capsulatum, Ciyptococcus neoformans and many others. The objective of this study is to investigate the in vitro and in vivo cytotoxicity of these two antifungal drugs. The in vitro and in vivo cytotoxicity of fluconazole and itraconazole were studied in thirty eight male Sprague Dawley rats. Freshly isolated rat hepatocytes were obtained for the in vitro treatment of fluconazole and itraconazole using a liver perfusion technique. The cell viability test was done by trypan blue exclusion. As a result, both fluconazole and itraconazole cause a reduction in cell viability of hepatocytes. However, itraconazole exerted its cytotoxicity more than fluconazole in both time- and dosedependent manner. Meanwhile, cytotoxicity of itraconazole was reduced significantly by Phenobarbital pretreatment. Phenobarbital did not have any effect on the .-. i l l cytotoxicity induced by fluconazole. In vivo studies revealed that rat's liver and kidney treated with repeated-doses of itraconazole showed a significantly higher in total protein in liver and kidney and significant increase in serum ALP and ALT activity. This is in agreement with histological findings that the rat treated with repeateddoses of itraconazole showed severe histological features compared to fluconazole. Morphological changes such as inflammation and fibrosis of liver were frequently seen in repeated-doses of itraconazole. This present study suggests that Phenobarbital plays a role in the cytoprotection of hepatocytes to itraconazole-induced but not fluconazole-induced cytotoxicity in vitro.
format Thesis
author Abdul Rahman, Nor Shahida
spellingShingle Abdul Rahman, Nor Shahida
Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
author_facet Abdul Rahman, Nor Shahida
author_sort Abdul Rahman, Nor Shahida
title Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
title_short Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
title_full Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
title_fullStr Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
title_full_unstemmed Toxicity of Antifungal Drugs Itraconazole and Fluconazole in Rats
title_sort toxicity of antifungal drugs itraconazole and fluconazole in rats
publishDate 2004
url http://psasir.upm.edu.my/id/eprint/6296/1/FPSK%28M%29_2004_8.pdf
http://psasir.upm.edu.my/id/eprint/6296/
_version_ 1781706623130009600
score 13.211869

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