AUTHOR=Chen Liyang , Han Zhijian , Shi Zhiguang , Liu Chao , Lu Qiulun 

TITLE=Melatonin Alleviates Renal Injury in Mouse Model of Sepsis

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.697643

DOI=10.3389/fphar.2021.697643

ISSN=1663-9812

ABSTRACT=<p>Melatonin (N-acetyl-5-methoxytryptamine; MLT) has been shown to have a renal-protective effect against kidney injury. However, the mechanisms underlying the protective role of MLT in sepsis-induced renal injury are yet to be revealed. In this study, MLT alleviated renal dysfunction with the increase of BUN (blood urea nitrogen) and SCR (serum creatinine) and reduction of fibrosis in the CLP (cecal ligation puncture) model. RNA-seq analysis showed that MLT repressed the oxidant stress in response to kidney injury. Our <italic>in vitro</italic> study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production <italic>via</italic> SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of <italic>Il-1α</italic>, <italic>Il-1β, Mcp-1</italic>, and <italic>Tgf-β1</italic>. Taken together, in evaluating the therapeutic effect of MLT on sepsis-induced acute kidney injury, the results showed that MLT alleviated renal damage by regulating the production of ROS.</p>