Role of p38 MAPK, Akt and NFκB in renoprotective effects of nebivolol on renal ischemia-reperfusion injury in rats

• Published in: Biotechnic & histochemistry 2023-08, Vol.98 (6), p.401-411
• Main Authors: Cavdar, Zahide, Kocak, Ayse, Ural, Cemre, Afagh, Aysan, Ersan, Sibel, Ozbal, Seda, Tatli, Merve, Celik, Asli, Arslan, Sevki, Cavdar, Caner
• Format: Article
• Language: English
• Subjects: Akt; ischemia; kidney; nebivolol; NFκB; p38 MAPK; rat; renoprotection; reperfusion
• ISSN: 1052-0295; 1473-7760
• DOI: 10.1080/10520295.2023.2212412

Renal ischemia-reperfusion (I-R) injury is a complex pathophysiologic condition characterized by oxidative stress, inflammation and apoptosis. We investigated the potential renoprotective effect of nebivolol, a β 1 adrenergic receptor blocker, against renal I-R injury. We focused on the role of nebivolol in activating p38 mitogen-activated protein kinase (MAPK) signaling, Akt (protein kinase B) and nuclear factor-κB (NFκB) transcription factors, which contribute to oxidative stress, inflammation and apoptosis during renal I-R. We divided 20 adult male Wistar albino rats into three experimental groups. Group 1 was a sham control in which only laparotomy was performed. Group 2 was the I-R group in which both kidneys were made ischemic for 45 min, then reperfused for 24 h. Group 3 was the I-R + nebivolol group in which 10 mg/kg nebivolol was administrated by gavage for 7 days before I-R. We measured Inflammation, oxidative stress and active caspase-3 as well as activation of p38 MAPK, Akt (protein kinase B) and NFκB transcription factor. Nebivolol significantly reduced oxidative stress and increased superoxide dismutase levels during renal I-R. We found that nebivolol significantly decreased interstitial inflammation, and TNF-α and interleukin-1β mRNA expression. Nebivolol significantly reduced active caspase-3 and kidney injury molecule-1 (KIM-1) expressions. Nebivolol also significantly decreased activation of p38 MAPK signaling and NFκB, and induced Akt activation during renal I-R. Our findings suggest that nebivolol may be useful for management of renal I-R injury.