In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum
Background & objectives: The leishmaniases are considered among the major infectious diseases affecting public health in several regions. There are many chemical agents which are effective in treatment of visceral leishmaniasis. But, overall treatment of visceral leishmaniasis is often difficult...
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Ardabil University of Medical Sciences
2014-09-01
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doaj-1747d09a01f14488971679bcca5144382020-11-25T02:25:16ZfasArdabil University of Medical SciencesJournal of Ardabil University of Medical Sciences2228-72802228-72992014-09-01143257265In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantumMohammad Hosein Razi Jalali0Somayeh Bahrami1Hosein Najafzadeh2Zeynab Asadi3 Background & objectives: The leishmaniases are considered among the major infectious diseases affecting public health in several regions. There are many chemical agents which are effective in treatment of visceral leishmaniasis. But, overall treatment of visceral leishmaniasis is often difficult. Thus, identification of new chemotherapeutic agents is important for treatment of disease. Since targeting of the ergosterol synthesis pathway of Leishmania may be useful therapeutically, the aim of this study was to investigate the effect of alone or in combination of amiodarone and ketoconazole on Leishmania infantum. Methods : To obtain logarithmic promastigotes of L. infantum, the parasites were cultured in BHI medium with FCS 10% together with antibiotics of penicillin and streptomycin and incubated at 24° C. Amastigote forms were obtained in BHI medium supplemented with 20% FCS at pH of 5.5 which incubated in 37° C. L.infantum susceptibility to amiodarone and ketoconazole was evaluated by proliferation of parasites in the absence or presence of these drugs with MTT assay. For evaluation of antiproliferative synergism against promastigotes and axenic amastigotes, fractional inhibitory concentrations (FIC) were calculated. An isobologram curve was constructed too. Results: Amiodarone produced a marked reduction in the viability of L.infantum promastigotes and axenic amastigotes. On the other hand ketoconazole induced a dose dependent effect on the parasites proliferation for promastigotes and axenic amastigotes. When the drugs were used in combination, the results indicated clear synergistic as shown by a concave isobologram and FIC value. Conclusion: The present study represents the evidence that the combination of amiodarone plus ketoconazole acts synergistically in controlling L. infantume in vitro. It is possible that amiodarone could be used in combination with ketoconazole to combat infection at low doses, thus reducing its side effects such as cardiotoxicity, thyroid dysfunction and pulmonary fibrosis.http://jarums.arums.ac.ir/browse.php?a_code=A-10-27-598&slc_lang=en&sid=1Amiodarone Ketoconazole Leishmania infantum In Vitro |
collection |
DOAJ |
language |
fas |
format |
Article |
sources |
DOAJ |
author |
Mohammad Hosein Razi Jalali Somayeh Bahrami Hosein Najafzadeh Zeynab Asadi |
spellingShingle |
Mohammad Hosein Razi Jalali Somayeh Bahrami Hosein Najafzadeh Zeynab Asadi In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum Journal of Ardabil University of Medical Sciences Amiodarone Ketoconazole Leishmania infantum In Vitro |
author_facet |
Mohammad Hosein Razi Jalali Somayeh Bahrami Hosein Najafzadeh Zeynab Asadi |
author_sort |
Mohammad Hosein Razi Jalali |
title |
In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum |
title_short |
In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum |
title_full |
In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum |
title_fullStr |
In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum |
title_full_unstemmed |
In Vitro Study on effects of Amiodarone and Ketoconazole on Leishmania infantum |
title_sort |
in vitro study on effects of amiodarone and ketoconazole on leishmania infantum |
publisher |
Ardabil University of Medical Sciences |
series |
Journal of Ardabil University of Medical Sciences |
issn |
2228-7280 2228-7299 |
publishDate |
2014-09-01 |
description |
Background & objectives: The leishmaniases are considered among the major infectious diseases affecting public health in several regions. There are many chemical agents which are effective in treatment of visceral leishmaniasis. But, overall treatment of visceral leishmaniasis is often difficult. Thus, identification of new chemotherapeutic agents is important for treatment of disease. Since targeting of the ergosterol synthesis pathway of Leishmania may be useful therapeutically, the aim of this study was to investigate the effect of alone or in combination of amiodarone and ketoconazole on Leishmania infantum. Methods : To obtain logarithmic promastigotes of L. infantum, the parasites were cultured in BHI medium with FCS 10% together with antibiotics of penicillin and streptomycin and incubated at 24° C. Amastigote forms were obtained in BHI medium supplemented with 20% FCS at pH of 5.5 which incubated in 37° C. L.infantum susceptibility to amiodarone and ketoconazole was evaluated by proliferation of parasites in the absence or presence of these drugs with MTT assay. For evaluation of antiproliferative synergism against promastigotes and axenic amastigotes, fractional inhibitory concentrations (FIC) were calculated. An isobologram curve was constructed too. Results: Amiodarone produced a marked reduction in the viability of L.infantum promastigotes and axenic amastigotes. On the other hand ketoconazole induced a dose dependent effect on the parasites proliferation for promastigotes and axenic amastigotes. When the drugs were used in combination, the results indicated clear synergistic as shown by a concave isobologram and FIC value. Conclusion: The present study represents the evidence that the combination of amiodarone plus ketoconazole acts synergistically in controlling L. infantume in vitro. It is possible that amiodarone could be used in combination with ketoconazole to combat infection at low doses, thus reducing its side effects such as cardiotoxicity, thyroid dysfunction and pulmonary fibrosis. |
topic |
Amiodarone Ketoconazole Leishmania infantum In Vitro |
url |
http://jarums.arums.ac.ir/browse.php?a_code=A-10-27-598&slc_lang=en&sid=1 |
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