Sevoflurane ameliorates LPS-induced inflammatory injury of HK-2 cells through Sirtuin1/NF-κB pathway

• Peipei Wang ^[1] ; Ping Wang ^[1] ; Miaomiao Yin ^[1] ; Shuo Wang ^[2]
  1. [1] Department of Anesthesiology, The First People’s Hospital of Lianyungang/The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, Jiangsu Province, China
  2. [2] Department of Anesthesiology, Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China
• Localización: Allergologia et immunopathologia: International journal for clinical and investigate allergology and clinical immunology, ISSN-e 1578-1267, ISSN 0301-0546, Vol. 50, Nº. 4, 2022, págs. 115-123
• Idioma: inglés
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• Resumen

  • he anesthetic sevoflurane (SEV) has been shown to protect against organ’s injury during sep-sis. The present study intended to uncover the protective effects of SEV on sepsis-induced acute kidney injury (SI-AKI) and its possible mechanism. Human renal tubular epithelial cell HK-2 was treated with 10 μg/mL lipopolysaccharide (LPS) to construct SI-AKI cell model. LPS-induced HK-2 cells were pretreated with SEV in the absence or presence of EX527, an inhibitor of Sirtuin 1 (SIRT1), after which were the detection of cell viability, lactate dehydrogenase (LDH) release, apoptosis, inflammation, and oxidative stress. Our results demonstrated that LPS caused decreased cell viability, increased LDH release, improved cell apoptosis along with decreased expression of Bcl2 and enhanced expressions of Bax, cleaved PARP and cleaved caspase, enhanced production, and protein expressions of TNF-α, IL-6, and IL-1β, increased generation of reactive oxygen species (ROS) and malondialdehyde (MDA), but contributed to declined activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). LPS inhibited SIRT1 and IκBα expressions but up-regulated p-NF-κB p65 and acetyl-p53 expressions as well. However, SEV pretreatment abolished all above-mentioned effects of LPS on HK-2 cells, while EX527 significantly reversed the effects of SEV. In conclusion, SEV effectively pro-tected HK-2 cells against LPS-induced apoptosis, inflammation, and oxidative stress, and these effects may depend on the increase of SIRT1 expression, thereby inactivating NF-κB signaling.