Klotho modulation by tempol: a potential therapeutic axis in sepsis
Abstract Background Sepsis is characterized by massive inflammatory and oxidative stress responses. The imbalance between oxidant and antioxidant activities during sepsis contributes to hyperinflammation, oxidation, endothelin system activation, and apoptosis, key elements of multiorgan failure. The...
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BMC
2025-07-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-025-04738-0 |
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| author | Alaa Al-kadi Aliaa F. Anter Remon Roshdy Rofaeil Mohamed M. Sayed-Ahmed Sara Mohamed Naguib Abdel Hafez Al-Shaimaa F. Ahmed |
| author_facet | Alaa Al-kadi Aliaa F. Anter Remon Roshdy Rofaeil Mohamed M. Sayed-Ahmed Sara Mohamed Naguib Abdel Hafez Al-Shaimaa F. Ahmed |
| author_sort | Alaa Al-kadi |
| collection | DOAJ |
| description | Abstract Background Sepsis is characterized by massive inflammatory and oxidative stress responses. The imbalance between oxidant and antioxidant activities during sepsis contributes to hyperinflammation, oxidation, endothelin system activation, and apoptosis, key elements of multiorgan failure. The current study investigated the role of tempol attenuating sepsis-induced acute cardiorenal injuries through modulation of Klotho. Method We used a cecal ligation and puncture (CLP) model of sepsis. Survival rate, histopathological assessment, and cardiorenal functions were analyzed. Oxidant and antioxidant activities, IL-6, and lactate were measured. The expression of tumor necrosis factor- α (TNF-α), p38-mitogen activating protein kinase (p38-MAPK), klotho, and caspase-3 were evaluated by immunohistochemistry. Results CLP caused acute cardiorenal damage, high mortality, upregulated levels of IL-6 and lactate, an imbalance in oxidant/antioxidant activities, elevated expression of TNF-α, p38, caspase-3, and reduced expression of klotho. Tempol improved survival, reduced inflammatory and oxidative stress parameters, improved cardiorenal functions, elevated the tissue contents of reduced glutathione (GSH) and superoxide dismutase (SOD), raised the expression of klotho protein and reduced the expression of p38, TNF- α and caspase-3. Conclusion Tempol is a promising agent against sepsis-induced organ damage. This was evident in its cardiorenal protective effect, up-regulation of klotho, suppression of inflammation, oxidation, and apoptosis, and enhancement of the antioxidant status. |
| format | Article |
| id | doaj-art-7477a6d1a7964d65b15da41abbd14a12 |
| institution | DOAJ |
| issn | 1471-2261 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj-art-7477a6d1a7964d65b15da41abbd14a122025-08-20T03:03:23ZengBMCBMC Cardiovascular Disorders1471-22612025-07-0125111210.1186/s12872-025-04738-0Klotho modulation by tempol: a potential therapeutic axis in sepsisAlaa Al-kadi0Aliaa F. Anter1Remon Roshdy Rofaeil2Mohamed M. Sayed-Ahmed3Sara Mohamed Naguib Abdel Hafez4Al-Shaimaa F. Ahmed5Department of Pharmacology and Toxicology, Faculty of Pharmacy, Deraya UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Minia UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Deraya UniversityPharmacology and Experimental Oncology Unit, National Cancer Institute, Cairo UniversityHistology and Cell Biology Department, Faculty of Medicine, Minia UniversityDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Minia UniversityAbstract Background Sepsis is characterized by massive inflammatory and oxidative stress responses. The imbalance between oxidant and antioxidant activities during sepsis contributes to hyperinflammation, oxidation, endothelin system activation, and apoptosis, key elements of multiorgan failure. The current study investigated the role of tempol attenuating sepsis-induced acute cardiorenal injuries through modulation of Klotho. Method We used a cecal ligation and puncture (CLP) model of sepsis. Survival rate, histopathological assessment, and cardiorenal functions were analyzed. Oxidant and antioxidant activities, IL-6, and lactate were measured. The expression of tumor necrosis factor- α (TNF-α), p38-mitogen activating protein kinase (p38-MAPK), klotho, and caspase-3 were evaluated by immunohistochemistry. Results CLP caused acute cardiorenal damage, high mortality, upregulated levels of IL-6 and lactate, an imbalance in oxidant/antioxidant activities, elevated expression of TNF-α, p38, caspase-3, and reduced expression of klotho. Tempol improved survival, reduced inflammatory and oxidative stress parameters, improved cardiorenal functions, elevated the tissue contents of reduced glutathione (GSH) and superoxide dismutase (SOD), raised the expression of klotho protein and reduced the expression of p38, TNF- α and caspase-3. Conclusion Tempol is a promising agent against sepsis-induced organ damage. This was evident in its cardiorenal protective effect, up-regulation of klotho, suppression of inflammation, oxidation, and apoptosis, and enhancement of the antioxidant status.https://doi.org/10.1186/s12872-025-04738-0SepsisOxidationTempolHeartKidneyKlotho |
| spellingShingle | Alaa Al-kadi Aliaa F. Anter Remon Roshdy Rofaeil Mohamed M. Sayed-Ahmed Sara Mohamed Naguib Abdel Hafez Al-Shaimaa F. Ahmed Klotho modulation by tempol: a potential therapeutic axis in sepsis BMC Cardiovascular Disorders Sepsis Oxidation Tempol Heart Kidney Klotho |
| title | Klotho modulation by tempol: a potential therapeutic axis in sepsis |
| title_full | Klotho modulation by tempol: a potential therapeutic axis in sepsis |
| title_fullStr | Klotho modulation by tempol: a potential therapeutic axis in sepsis |
| title_full_unstemmed | Klotho modulation by tempol: a potential therapeutic axis in sepsis |
| title_short | Klotho modulation by tempol: a potential therapeutic axis in sepsis |
| title_sort | klotho modulation by tempol a potential therapeutic axis in sepsis |
| topic | Sepsis Oxidation Tempol Heart Kidney Klotho |
| url | https://doi.org/10.1186/s12872-025-04738-0 |
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