Desflurane suppresses inflammation and oxidative stress via targeting the Keap1/Nrf2/ARE pathway in acute kidney injury

Sepsis-associated acute kidney injury (SA-AKI) is characterized by suddenly decreased renal function and urinary volume. Desflurane, an inhalational anesthetic, is reported to possess antioxidant and anti-inflammatory properties. We aim to investigate the roles and mechanisms of desflurane in SA-AKI. SA-AKI was induced in 8-week-old Sprague Dawley rats by cecal ligation and puncture (CLP), either with or without desflurane treatment. Renal function was detected by measuring blood urea nitrogen (BUN) and serum creatinine (Scr). Oxidative and inflammatory markers were determined using commercial kits. Apoptosis was evaluated using TUNEL assay, immunohistochemical staining for cleaved caspase-3, and western blotting. The expression of Nrf2-ARE pathway-related proteins was evaluated using western blotting and immunohistochemical staining. Desflurane inhibited the CLP-induced reduction in survival rate and elevation in BUN and Scr levels. Additionally, desflurane suppressed inflammation and oxidative stress in CLP-induced SA-AKI rats, as indicated by the upregulated levels of MDA and inflammatory markers and MPO activity as well as downregulated GSH, SOD, and CAT activities. Moreover, desflurane reduced apoptosis by downregulating Bax, cleaved caspase-3, and cleaved caspase-9 protein levels while upregulating Bcl-2 protein levels in renal tissues of SA-AKI rats. Furthermore, desflurane pretreatment is closely associated with the activation of Keap1/Nrf2/ARE signaling in CLP-induced SA-AKI rats. To conclude, desflurane ameliorates inflammation, apoptosis and oxidative stress in SA-AKI models, which is mechanistically linked to the Keap1/Nrf2/ARE pathway.