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N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma
BACKGROUND: Nephrotoxicity is one of the known side effects of methotrexate (MTX) therapy despite the use of conventional protective measures. Our objectives were to evaluate the effects of N-acetylcysteine (NAC) on MTX-induced toxicity in renal tubular cells and to evaluate whether adjunctive use o...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711223/ https://www.ncbi.nlm.nih.gov/pubmed/26811594 http://dx.doi.org/10.4103/0971-5851.171545 |
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author | Singh, Ruchi Shah, Rikin Turner, Curtis Regueira, Osvaldo Vasylyeva, Tetyana L. |
author_facet | Singh, Ruchi Shah, Rikin Turner, Curtis Regueira, Osvaldo Vasylyeva, Tetyana L. |
author_sort | Singh, Ruchi |
collection | PubMed |
description | BACKGROUND: Nephrotoxicity is one of the known side effects of methotrexate (MTX) therapy despite the use of conventional protective measures. Our objectives were to evaluate the effects of N-acetylcysteine (NAC) on MTX-induced toxicity in renal tubular cells and to evaluate whether adjunctive use of NAC interferes with MTX antitumor activity in the B-cell lymphoma. METHODS: Kidney Epithelial (Madin-Darby canine kidney [MDCK]) cells were exposed to MTX (10 μM or 100 μM) alone and with NAC (0.2 mM or 0.4 mM). Reactive oxygen species (ROS) generation at 1, 2, 4, and 24 h was measured by flow cytometer. Quantification of total glutathione (GSH) was performed by using GSH assay kit. To measure the impact of NAC on the antitumor activity of MTX, B lymphoma cells were exposed to MTX alone and with NAC. A percentage of apoptosis was measured using fluorescein isothiocyanate in both cell lines. Quantitative data was presented as a means ± standard deviation, and P values were analyzed using the Student's t-test. RESULTS: Apoptosis in MDCK cells were observed after 24 h of incubation with both 10 μM and 100 μM MTX. Maximum ROS generation was observed at 4 h and corresponded to GSH production. Treatment with 0.2 and 0.4 mM of NAC led to decrease percentages of apoptotic MDCK cells. NAC did not change either proliferation or apoptosis of B-cell lymphoma. CONCLUSION: Using NAC for kidney protection may not interfere with the antitumor activity of MTX. Further in vivo studies are warranted to confirm noninterference between MTX and NAC and assess synergistic antitumor effects. |
format | Online Article Text |
id | pubmed-4711223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47112232016-01-25 N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma Singh, Ruchi Shah, Rikin Turner, Curtis Regueira, Osvaldo Vasylyeva, Tetyana L. Indian J Med Paediatr Oncol Original Article BACKGROUND: Nephrotoxicity is one of the known side effects of methotrexate (MTX) therapy despite the use of conventional protective measures. Our objectives were to evaluate the effects of N-acetylcysteine (NAC) on MTX-induced toxicity in renal tubular cells and to evaluate whether adjunctive use of NAC interferes with MTX antitumor activity in the B-cell lymphoma. METHODS: Kidney Epithelial (Madin-Darby canine kidney [MDCK]) cells were exposed to MTX (10 μM or 100 μM) alone and with NAC (0.2 mM or 0.4 mM). Reactive oxygen species (ROS) generation at 1, 2, 4, and 24 h was measured by flow cytometer. Quantification of total glutathione (GSH) was performed by using GSH assay kit. To measure the impact of NAC on the antitumor activity of MTX, B lymphoma cells were exposed to MTX alone and with NAC. A percentage of apoptosis was measured using fluorescein isothiocyanate in both cell lines. Quantitative data was presented as a means ± standard deviation, and P values were analyzed using the Student's t-test. RESULTS: Apoptosis in MDCK cells were observed after 24 h of incubation with both 10 μM and 100 μM MTX. Maximum ROS generation was observed at 4 h and corresponded to GSH production. Treatment with 0.2 and 0.4 mM of NAC led to decrease percentages of apoptotic MDCK cells. NAC did not change either proliferation or apoptosis of B-cell lymphoma. CONCLUSION: Using NAC for kidney protection may not interfere with the antitumor activity of MTX. Further in vivo studies are warranted to confirm noninterference between MTX and NAC and assess synergistic antitumor effects. Medknow Publications & Media Pvt Ltd 2015 /pmc/articles/PMC4711223/ /pubmed/26811594 http://dx.doi.org/10.4103/0971-5851.171545 Text en Copyright: © Indian Journal of Medical and Paediatric Oncology http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Singh, Ruchi Shah, Rikin Turner, Curtis Regueira, Osvaldo Vasylyeva, Tetyana L. N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title | N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title_full | N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title_fullStr | N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title_full_unstemmed | N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title_short | N-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on B-cell lymphoma |
title_sort | n-acetylcysteine renoprotection in methotrexate induced nephrotoxicity and its effects on b-cell lymphoma |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4711223/ https://www.ncbi.nlm.nih.gov/pubmed/26811594 http://dx.doi.org/10.4103/0971-5851.171545 |
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