AUTHOR=Li Jiameng , Zhang Zhuyun , Wang Liya , Jiang Luojia , Qin Zheng , Zhao Yuliang , Su Baihai 

TITLE=Maresin 1 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury via Inhibiting NOX4/ROS/NF-κB Pathway

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.782660

DOI=10.3389/fphar.2021.782660

ISSN=1663-9812

ABSTRACT=Sepsis-associated acute kidney injury (S-AKI) is a common complication in hospitalized and critically ill patients, which increases the risk of multiple comorbidities and is associated with extremely high mortality. MaR1, a lipid mediators derived from the omega-3 fatty acid docosahexaenoic acid (DHA), has been reported to protect against the inflammation and promote the regression of acute inflammation. This study proposed to systematically investigate the renoprotective effects and potential molecular mechanism of MaR1 in septic AKI. We established S-AKI animal model by a single intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg on male C57BL/6J mice. LPS-stimulated (100 μg/ml) mouse kidney tubular epithelium cells (TCMK-1) were used to simulate septic AKI in vitro. The results showed that pretreatment with MaR1 significantly reduced serum creatinine and blood urea nitrogen levels as well as tubular damage scores and injury marker NGAL in septic AKI mice. Meanwhile, MaR1 administration obviously diminished pro-inflammatory cytokines (TNF-α, IL-6, IL-1β and MCP-1), downregulated BAX and cleaved caspase-3 expression and upregulated BCL‐2 expression in the injured kidney tissues and TCMK-1 cells. In addition, MaR1 reduced MDA production and improved SOD activity of renal tissues while inhibiting ROS production and protecting mitochondria. Mechanistically, LPS stimulated the expression of NOX4/ROS/NF-κB p65 signaling pathway in S-AKI kidneys, while MaR1 effectively suppressed the activation of corresponding pathway. In conclusion, MaR1 attenuated kidney inflammation, apoptosis, oxidative stress and mitochondrial dysfunction to protect against LPS-induced septic AKI via inhibiting NOX4/ROS/NF-κB p65 signaling pathway.