Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway
Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI ind...
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2025-05-01
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| author | Neslihan Şahin Ejder Saylav Bora Osman Sezer Çınaroğlu Oytun Erbaş |
| author_facet | Neslihan Şahin Ejder Saylav Bora Osman Sezer Çınaroğlu Oytun Erbaş |
| author_sort | Neslihan Şahin |
| collection | DOAJ |
| description | Sepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation. |
| format | Article |
| id | doaj-art-0b26de46a09e46ff8627a3472dc44b3a |
| institution | DOAJ |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-0b26de46a09e46ff8627a3472dc44b3a2025-08-20T03:14:42ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147534010.3390/cimb47050340Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 PathwayNeslihan Şahin0Ejder Saylav Bora1Osman Sezer Çınaroğlu2Oytun Erbaş3Department of Emergency Medicine, Bergama State Hospital, 35700 Izmir, TurkeyDepartment of Emergency Medicine, Faculty of Medicine, Izmir Katip Çelebi University, 35620 Izmir, TurkeyDepartment of Emergency Medicine, Faculty of Medicine, Izmir Katip Çelebi University, 35620 Izmir, TurkeyFaculty of Medicine, Biruni Research Center (BAMER), Biruni University, 34015 Istanbul, TurkeySepsis-associated acute kidney injury (S-AKI) is a severe complication in critically ill patients, marked by inflammation, oxidative stress, and renal dysfunction. This study aimed to evaluate the renoprotective effects of Fasudil (Fas), a Rho-associated kinase inhibitor, in a rat model of S-AKI induced by cecal ligation and puncture (CLP). Thirty-six Wistar albino rats were divided into control, CLP with saline, and Fas (100 mg/kg/day intraperitoneally) groups. Biochemical, histopathological, and molecular analyses were conducted to assess kidney function, oxidative stress, and inflammation. Fas treatment significantly decreased plasma malondialdehyde and TNF-α levels, reducing oxidative stress and systemic inflammation. Kidney function markers, including BUN and creatinine, showed marked improvement. Furthermore, Fas suppressed the expression of STAT-3 and NLRP-3 in renal tissues, highlighting its role in modulating key inflammatory pathways. Histological evaluation revealed alleviated renal damage, with less tubular necrosis and interstitial inflammation in the Fas-treated group. In conclusion, Fas demonstrates significant anti-inflammatory, antioxidant, and nephroprotective effects in S-AKI, primarily by inhibiting STAT-3 and NLRP-3 signaling. These results support its potential as a therapeutic agent in sepsis-induced kidney injury and suggest the need for further clinical evaluation.https://www.mdpi.com/1467-3045/47/5/340sepsis-associated acute kidney injuryFasudilSTAT-3 pathwayNLRP-3 inflammasomeRho kinase inhibitor |
| spellingShingle | Neslihan Şahin Ejder Saylav Bora Osman Sezer Çınaroğlu Oytun Erbaş Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway Current Issues in Molecular Biology sepsis-associated acute kidney injury Fasudil STAT-3 pathway NLRP-3 inflammasome Rho kinase inhibitor |
| title | Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway |
| title_full | Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway |
| title_fullStr | Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway |
| title_full_unstemmed | Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway |
| title_short | Rho-Associated Kinase Inhibitor Fasudil Protects from Sepsis-Induced Acute Kidney Injury in Rat via Suppressing STAT-3 and NLRP-3 Pathway |
| title_sort | rho associated kinase inhibitor fasudil protects from sepsis induced acute kidney injury in rat via suppressing stat 3 and nlrp 3 pathway |
| topic | sepsis-associated acute kidney injury Fasudil STAT-3 pathway NLRP-3 inflammasome Rho kinase inhibitor |
| url | https://www.mdpi.com/1467-3045/47/5/340 |
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