TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway
Objective This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI.Methods The rats were divided into...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2313176 |
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| author | Yan-mei Xia Yu-qian Guan Ji-fang Liang Wei-dong Wu |
| author_facet | Yan-mei Xia Yu-qian Guan Ji-fang Liang Wei-dong Wu |
| author_sort | Yan-mei Xia |
| collection | DOAJ |
| description | Objective This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI.Methods The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot.Results Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group.Conclusion TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI. |
| format | Article |
| id | doaj-art-535110157df24377afd50559a4bcfc3e |
| institution | Kabale University |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-535110157df24377afd50559a4bcfc3e2025-01-23T04:17:48ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2313176TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathwayYan-mei Xia0Yu-qian Guan1Ji-fang Liang2Wei-dong Wu3Department of Critical, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, PR ChinaDepartment of Critical, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, PR ChinaDepartment of Critical, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, PR ChinaDepartment of Critical, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, PR ChinaObjective This study was designed to observe the effect of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway activity on sepsis-associated acute kidney injury (SA-AKI), thereby providing new considerations for the prevention and treatment of SA-AKI.Methods The rats were divided into Sham, cecal ligation and puncture (CLP), CLP + vehicle, and CLP + TAK-242 groups. Except the Sham group, a model of CLP-induced sepsis was established in other groups. After 24 h, the indicators related to kidney injury in blood samples were detected. The pathological changes in the kidneys were observed by hematoxylin-eosin staining, and tubular damage was scored. Oxidative stress-related factors, mitochondrial dysfunction-related indicators in each group were measured; the levels of inflammatory factors in serum and kidney tissue of rats were examined. Finally, the expression of proteins related to the TLR4/NF-κB signaling pathway was observed by western blot.Results Compared with the CLP + vehicle and CLP + TAK-242 groups, the CLP + TAK-242 group reduced blood urea nitrogen (BUN), creatinine (Cr), cystatin-C (Cys-C), reactive oxygen species (ROS), malondialdehyde (MDA), and inflammatory factors levels (p < 0.01), as well as increased superoxide dismutase (SOD) activity of CLP rats (p < 0.01). Additionally, TAK-242 treatment improved the condition of CLP rats that had glomerular and tubular injuries and mitochondrial disorders (p < 0.01). Further mechanism research revealed that TAK-242 can inhibit the TLR4/NF-κB signaling pathway activated by CLP (p < 0.01). Above indicators after TAK-242 treatment were close to those of the Sham group.Conclusion TAK-242 can improve oxidative stress, mitochondrial dysfunction, and inflammatory response by inhibiting the activity of TLR4/NF-κB signaling pathway, thereby preventing rats from SA-AKI.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2313176Sepsis-associated acute kidney injury (SA-AKI)TAK-242oxidative stressmitochondrial dysfunctioninflammatory factorstoll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway |
| spellingShingle | Yan-mei Xia Yu-qian Guan Ji-fang Liang Wei-dong Wu TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway Renal Failure Sepsis-associated acute kidney injury (SA-AKI) TAK-242 oxidative stress mitochondrial dysfunction inflammatory factors toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway |
| title | TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway |
| title_full | TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway |
| title_fullStr | TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway |
| title_full_unstemmed | TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway |
| title_short | TAK-242 improves sepsis-associated acute kidney injury in rats by inhibiting the TLR4/NF-κB signaling pathway |
| title_sort | tak 242 improves sepsis associated acute kidney injury in rats by inhibiting the tlr4 nf κb signaling pathway |
| topic | Sepsis-associated acute kidney injury (SA-AKI) TAK-242 oxidative stress mitochondrial dysfunction inflammatory factors toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) signaling pathway |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2024.2313176 |
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