NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-04785-z |
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| author | Juheb Akhter Jasim Khan Madhu Baghel Mirza Masroor Ali Beg Poonam Goswami Mohd Amir Afjal Shahzad Ahmad Haroon Habib Abul Kalam Najmi Sheikh Raisuddin |
| author_facet | Juheb Akhter Jasim Khan Madhu Baghel Mirza Masroor Ali Beg Poonam Goswami Mohd Amir Afjal Shahzad Ahmad Haroon Habib Abul Kalam Najmi Sheikh Raisuddin |
| author_sort | Juheb Akhter |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-23T11:46:49Z |
| format | Article |
| id | doaj.art-04b1585128c74261beb8dfc2ce0eb0bb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T11:46:49Z |
| publishDate | 2022-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-04b1585128c74261beb8dfc2ce0eb0bb2022-12-21T17:48:20ZengNature PortfolioScientific Reports2045-23222022-01-0112111510.1038/s41598-022-04785-zNLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in miceJuheb Akhter0Jasim Khan1Madhu Baghel2Mirza Masroor Ali Beg3Poonam Goswami4Mohd Amir Afjal5Shahzad Ahmad6Haroon Habib7Abul Kalam Najmi8Sheikh Raisuddin9Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Metabolic Research Laboratory, National Institute of ImmunologyMolecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University)Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University)Abstract 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.https://doi.org/10.1038/s41598-022-04785-z |
| spellingShingle | Juheb Akhter Jasim Khan Madhu Baghel Mirza Masroor Ali Beg Poonam Goswami Mohd Amir Afjal Shahzad Ahmad Haroon Habib Abul Kalam Najmi Sheikh Raisuddin NLRP3 inflammasome in rosmarinic acid-afforded attenuation of acute kidney injury in mice Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-04785-z |
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