Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway
Abstract Tamoxifen (TAM) is extensively used to manage estrogen receptor-positive breast cancer. Despite its effectiveness, its administration can negatively impact various organs, including the liver. This research focused on the effects of TAM on the pyroptotic pathway in the liver and evaluated t...
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2025-02-01
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author | Wedad S. Sarawi Hala A. Attia Afraa Alzoubi Nour Alanazi Raeesa Mohammad Rehab A. Ali |
author_facet | Wedad S. Sarawi Hala A. Attia Afraa Alzoubi Nour Alanazi Raeesa Mohammad Rehab A. Ali |
author_sort | Wedad S. Sarawi |
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description | Abstract Tamoxifen (TAM) is extensively used to manage estrogen receptor-positive breast cancer. Despite its effectiveness, its administration can negatively impact various organs, including the liver. This research focused on the effects of TAM on the pyroptotic pathway in the liver and evaluated the potential of cardamom extract (CRDE) to lessen hepatic damage of TAM in female rats. Rats received 45 mg/kg of TAM injections for 10 days, while the groups treated with CRDE received 12 ml/kg of CRDE for 20 days, commencing 10 days before TAM administration. TAM exposure resulted in apparent degenerations in hepatic tissue with inflammatory cell infiltration and loss of architectures. Serum levels of liver enzymes including alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were elevated, along with hepatic oxidative stress, as shown by increased lipid peroxidation with lower levels of reduced glutathione. TAM caused inflammation in the liver tissue as indicated by higher levels of tumor necrosis factor-α and interleukin-6 as well as increased expression of CD68; a phagocytic Kupffer’s cells marker. Additionally, the protein expression analysis revealed a high expression of pyroptotic markers including NLRP3-inflammasome, caspase-1, and gasdermin D. Conversely, CRDE treatment effectively neutralized the biochemical, histological, and protein expression alterations induced by TAM. In conclusion, CRDE demonstrated the potential to protect the liver from TAM-induced damage by regulating mechanisms involving oxidative damage, inflammation, and pyroptosis. |
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institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2025-02-01 |
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spelling | doaj-art-d29745702d4840f3bf613ed48a4c47672025-02-09T12:36:21ZengNature PortfolioScientific Reports2045-23222025-02-0115111510.1038/s41598-025-89091-0Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathwayWedad S. Sarawi0Hala A. Attia1Afraa Alzoubi2Nour Alanazi3Raeesa Mohammad4Rehab A. Ali5Department of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityDepartment of Bioengineering, Imperial College LondonCollege of Pharmacy, King Saud UniversityDepartment of Histology, College of Medicine, King Saud UniversityDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud UniversityAbstract Tamoxifen (TAM) is extensively used to manage estrogen receptor-positive breast cancer. Despite its effectiveness, its administration can negatively impact various organs, including the liver. This research focused on the effects of TAM on the pyroptotic pathway in the liver and evaluated the potential of cardamom extract (CRDE) to lessen hepatic damage of TAM in female rats. Rats received 45 mg/kg of TAM injections for 10 days, while the groups treated with CRDE received 12 ml/kg of CRDE for 20 days, commencing 10 days before TAM administration. TAM exposure resulted in apparent degenerations in hepatic tissue with inflammatory cell infiltration and loss of architectures. Serum levels of liver enzymes including alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were elevated, along with hepatic oxidative stress, as shown by increased lipid peroxidation with lower levels of reduced glutathione. TAM caused inflammation in the liver tissue as indicated by higher levels of tumor necrosis factor-α and interleukin-6 as well as increased expression of CD68; a phagocytic Kupffer’s cells marker. Additionally, the protein expression analysis revealed a high expression of pyroptotic markers including NLRP3-inflammasome, caspase-1, and gasdermin D. Conversely, CRDE treatment effectively neutralized the biochemical, histological, and protein expression alterations induced by TAM. In conclusion, CRDE demonstrated the potential to protect the liver from TAM-induced damage by regulating mechanisms involving oxidative damage, inflammation, and pyroptosis.https://doi.org/10.1038/s41598-025-89091-0TamoxifenCardamom extractLiver damageCD68Liver inflammationPyroptosis |
spellingShingle | Wedad S. Sarawi Hala A. Attia Afraa Alzoubi Nour Alanazi Raeesa Mohammad Rehab A. Ali Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway Scientific Reports Tamoxifen Cardamom extract Liver damage CD68 Liver inflammation Pyroptosis |
title | Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway |
title_full | Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway |
title_fullStr | Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway |
title_full_unstemmed | Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway |
title_short | Cardamom extract alleviates tamoxifen-induced liver damage by suppressing inflammation and pyroptosis pathway |
title_sort | cardamom extract alleviates tamoxifen induced liver damage by suppressing inflammation and pyroptosis pathway |
topic | Tamoxifen Cardamom extract Liver damage CD68 Liver inflammation Pyroptosis |
url | https://doi.org/10.1038/s41598-025-89091-0 |
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