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NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice

Cisplatin (CP) is a well-known anticancer drug used to effectively treat various kinds of solid tumors. CP causes acute kidney injury (AKI) and unfortunately, there is no therapeutic approach in hand to prevent AKI. Several signaling pathways are responsible for inducing AKI which leads to inflammat...

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Autores principales: Akhter, Juheb, Khan, Jasim, Baghel, Madhu, Beg, Mirza Masroor Ali, Goswami, Poonam, Afjal, Mohd Amir, Ahmad, Shahzad, Habib, Haroon, Najmi, Abul Kalam, Raisuddin, Sheikh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789898/
https://www.ncbi.nlm.nih.gov/pubmed/35079027
http://dx.doi.org/10.1038/s41598-022-04785-z
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author Akhter, Juheb
Khan, Jasim
Baghel, Madhu
Beg, Mirza Masroor Ali
Goswami, Poonam
Afjal, Mohd Amir
Ahmad, Shahzad
Habib, Haroon
Najmi, Abul Kalam
Raisuddin, Sheikh
author_facet Akhter, Juheb
Khan, Jasim
Baghel, Madhu
Beg, Mirza Masroor Ali
Goswami, Poonam
Afjal, Mohd Amir
Ahmad, Shahzad
Habib, Haroon
Najmi, Abul Kalam
Raisuddin, Sheikh
author_sort Akhter, Juheb
collection PubMed
description Cisplatin (CP) is a well-known anticancer drug used to effectively treat various kinds of solid tumors. CP causes acute kidney injury (AKI) and unfortunately, there is no therapeutic approach in hand to prevent AKI. Several signaling pathways are responsible for inducing AKI which leads to inflammation in proximal convoluted tubule cells in the kidney. Furthermore, the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is involved in the CP-induced AKI. In this study, we investigated therapeutic effects of rosmarinic acid (RA) against inflammation-induced AKI. RA was orally administered at the dose of 100 mg/kg for two consecutive days after 24 h of a single injection of CP at the dose of 20 mg/kg administered intraperitoneally in Swiss albino male mice. Treatment of RA inhibited the activation of NLRP3 signaling pathway by blocking the activated caspase-1 and downstream signal molecules such as IL-1β and IL18. CP activated HMGB1-TLR4/MyD88 axis was also found to be downregulated with the RA treatment. Activation of nuclear factor-κB and elevated protein expression of cyclooxygenase-2 (COX-2) were also found to be downregulated in RA-treated animals. Alteration of early tubular injury biomarker, kidney injury molecule-1 (KIM-1), was found to be subsided in RA-treated mice. RA has been earlier reported for antioxidant and anti-inflammatory properties. Our findings show that blocking a critical step of inflammasome signaling pathway by RA treatment can be a novel and beneficial approach to prevent the CP-induced AKI.
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spelling pubmed-87898982022-01-27 NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice Akhter, Juheb Khan, Jasim Baghel, Madhu Beg, Mirza Masroor Ali Goswami, Poonam Afjal, Mohd Amir Ahmad, Shahzad Habib, Haroon Najmi, Abul Kalam Raisuddin, Sheikh Sci Rep Article Cisplatin (CP) is a well-known anticancer drug used to effectively treat various kinds of solid tumors. CP causes acute kidney injury (AKI) and unfortunately, there is no therapeutic approach in hand to prevent AKI. Several signaling pathways are responsible for inducing AKI which leads to inflammation in proximal convoluted tubule cells in the kidney. Furthermore, the nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is involved in the CP-induced AKI. In this study, we investigated therapeutic effects of rosmarinic acid (RA) against inflammation-induced AKI. RA was orally administered at the dose of 100 mg/kg for two consecutive days after 24 h of a single injection of CP at the dose of 20 mg/kg administered intraperitoneally in Swiss albino male mice. Treatment of RA inhibited the activation of NLRP3 signaling pathway by blocking the activated caspase-1 and downstream signal molecules such as IL-1β and IL18. CP activated HMGB1-TLR4/MyD88 axis was also found to be downregulated with the RA treatment. Activation of nuclear factor-κB and elevated protein expression of cyclooxygenase-2 (COX-2) were also found to be downregulated in RA-treated animals. Alteration of early tubular injury biomarker, kidney injury molecule-1 (KIM-1), was found to be subsided in RA-treated mice. RA has been earlier reported for antioxidant and anti-inflammatory properties. Our findings show that blocking a critical step of inflammasome signaling pathway by RA treatment can be a novel and beneficial approach to prevent the CP-induced AKI. Nature Publishing Group UK 2022-01-25 /pmc/articles/PMC8789898/ /pubmed/35079027 http://dx.doi.org/10.1038/s41598-022-04785-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Akhter, Juheb
Khan, Jasim
Baghel, Madhu
Beg, Mirza Masroor Ali
Goswami, Poonam
Afjal, Mohd Amir
Ahmad, Shahzad
Habib, Haroon
Najmi, Abul Kalam
Raisuddin, Sheikh
NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title_full NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title_fullStr NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title_full_unstemmed NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title_short NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
title_sort nlrp3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8789898/
https://www.ncbi.nlm.nih.gov/pubmed/35079027
http://dx.doi.org/10.1038/s41598-022-04785-z
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