Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis.
BACKGROUND: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have...
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ftdoajarticles:oai:doaj.org/article:d948cfd2cd3d4c4dbf11ec6d8a2443f5 2023-05-15T15:16:04+02:00 Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. Meenakshi Sharma Rakesh Sehgal Sukhbir Kaur 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001629 https://doaj.org/article/d948cfd2cd3d4c4dbf11ec6d8a2443f5 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3341342?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001629 https://doaj.org/article/d948cfd2cd3d4c4dbf11ec6d8a2443f5 PLoS Neglected Tropical Diseases, Vol 6, Iss 5, p e1629 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001629 2022-12-31T14:10:15Z BACKGROUND: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants. METHODOLOGY/PRINCIPAL FINDINGS: The present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight) and its combination with different antioxidants (vitamin C, vitamin E and silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated. CONCLUSION/SIGNIFICANCE: A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2) with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as compared to those treated with the drug only. The above results are ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 5 e1629 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Meenakshi Sharma Rakesh Sehgal Sukhbir Kaur Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Most available drugs against visceral leishmaniasis are toxic, and growing limitations in available chemotherapeutic strategies due to emerging resistant strains and lack of an effective vaccine against visceral leishmaniasis deepens the crisis. Antineoplastic drugs like miltefosine have in the past been effective against the parasitic infections. An antineoplastic drug, cisplatin (cis-diamminedichloroplatinum II; CDDP), is recognized as a DNA-damaging drug which also induces alteration of cell-cycle in both promastigotes and amastigotes leading to cell death. First in vivo reports from our laboratory revealed the leishmanicidal potential of cisplatin. However, high doses of cisplatin produce impairment of kidney, which can be reduced by the administration of antioxidants. METHODOLOGY/PRINCIPAL FINDINGS: The present study was designed to evaluate the antileishmanial effect of cisplatin at higher doses (5 mg and 2.5 mg/kg body weight) and its combination with different antioxidants (vitamin C, vitamin E and silibinin) so as to eliminate the parasite completely and reduce the toxicity. In addition, various immunological, hematological and biochemical changes induced by it in uninfected and Leishmania donovani infected BALB/c mice were investigated. CONCLUSION/SIGNIFICANCE: A significant reduction in parasite load, higher IgG2a and lower IgG1 levels, enhanced DTH responses, and greater concentration of Th1 cytokines (IFN-γ, IL-2) with a concomitant down regulation of IL-10 and IL-4 pointed towards the generation of the protective Th1 type of immune response. A combination of cisplatin with antioxidants resulted in successful reduction of nephrotoxicity by normalizing the enzymatic levels of various liver and kidney function tests. Reduction in parasite load, increase in Th1 type of immune responses, and normalization of various biochemical parameters occurred in animals treated with cisplatin in combination with various antioxidants as compared to those treated with the drug only. The above results are ... |
format |
Article in Journal/Newspaper |
author |
Meenakshi Sharma Rakesh Sehgal Sukhbir Kaur |
author_facet |
Meenakshi Sharma Rakesh Sehgal Sukhbir Kaur |
author_sort |
Meenakshi Sharma |
title |
Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
title_short |
Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
title_full |
Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
title_fullStr |
Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
title_full_unstemmed |
Evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
title_sort |
evaluation of nephroprotective and immunomodulatory activities of antioxidants in combination with cisplatin against murine visceral leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001629 https://doaj.org/article/d948cfd2cd3d4c4dbf11ec6d8a2443f5 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 5, p e1629 (2012) |
op_relation |
http://europepmc.org/articles/PMC3341342?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001629 https://doaj.org/article/d948cfd2cd3d4c4dbf11ec6d8a2443f5 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001629 |
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PLoS Neglected Tropical Diseases |
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6 |
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5 |
container_start_page |
e1629 |
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