Melatonin Alleviates Renal Injury in Mouse Model of Sepsis

被引:21
作者
Chen, Liyang [1 ]
Han, Zhijian [2 ]
Shi, Zhiguang [1 ]
Liu, Chao [3 ]
Lu, Qiulun [1 ]
机构
[1] Nanjing Med Univ, Sch Pharm, Key Lab Cardiovasc & Cerebrovasc Med, Nanjing, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Dept Urol, Nanjing, Peoples R China
[3] Hubei Univ Sci & Technol, Hubei Key Lab Diabet & Angiopathy, Xianning, Peoples R China
基金
中国国家自然科学基金;
关键词
melatonin; sepsis; ROS (reactive oxygen species); acute kidney injury; renal dysfunction; ACUTE KIDNEY INJURY; RATS;
D O I
10.3389/fphar.2021.697643
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 in vitro study showed that MLT suppresses LPS-induced accumulation of ROS (reactive oxygen species) production via SOD2 downregulation and Nox4 upregulation in HK-2 cells. Furthermore, we found that MLT alleviated the inflammatory response, with the mRNA-level reduction of Il-1 alpha, Il-1 beta, Mcp-1, and Tgf-beta 1. 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.
引用
收藏
页数:8
相关论文
共 22 条
[11]   Melatonin and brain inflammaging [J].
Hardeland, Ruediger ;
Cardinali, Daniel P. ;
Brown, Gregory M. ;
Pandi-Perumal, Seithikurippu R. .
PROGRESS IN NEUROBIOLOGY, 2015, 127 :46-63
[12]   Melatonin Attenuates Cisplatin-Induced Acute Kidney Injury through Dual Suppression of Apoptosis and Necroptosis [J].
Kim, Jong Woo ;
Jo, Jungmin ;
Kim, Jung-Yeon ;
Choe, Misun ;
Leem, Jaechan ;
Park, Jae-Hyung .
BIOLOGY-BASEL, 2019, 8 (03)
[13]   Melatonin suppresses tumor progression by reducing angiogenesis stimulated by HIF-1 in a mouse tumor model [J].
Kim, Kil-Jung ;
Choi, Jae-Sun ;
Kang, Insug ;
Kim, Kyu-Won ;
Jeong, Chul-Ho ;
Jeong, Joo-Won .
JOURNAL OF PINEAL RESEARCH, 2013, 54 (03) :264-270
[14]   Melatonin attenuates cisplatin-induced acute kidney injury in rats via induction of anti-aging protein, Klotho [J].
Ko, Je-Won ;
Shin, Na-Rae ;
Jung, Tae-Yang ;
Shin, In-Sik ;
Moon, Changjong ;
Kim, Sung-Ho ;
Lee, In-Chul ;
Kim, Sung-Hwan ;
Yun, Won-Kee ;
Kim, Hyoung-Chin ;
Kim, Jong-Choon .
FOOD AND CHEMICAL TOXICOLOGY, 2019, 129 :201-210
[15]   Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes [J].
Maleki Dana, Parisa ;
Reiter, Russel J. ;
Hallajzadeh, Jamal ;
Asemi, Zatollah ;
Mansournia, Mohammad Ali ;
Yousefi, Bahman .
IUBMB LIFE, 2020, 72 (11) :2355-2365
[16]  
Maung Stephanie C, 2016, World J Nephrol, V5, P224, DOI 10.5527/wjn.v5.i3.224
[17]   The roles of melatonin on kidney injury in obese and diabetic conditions [J].
Promsan, Sasivimon ;
Lungkaphin, Anusorn .
BIOFACTORS, 2020, 46 (04) :531-549
[18]   Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model [J].
Puig, Angela ;
Rancan, Lisa ;
Paredes, Sergio D. ;
Carrasco, Adrian ;
Escames, Germaine ;
Vara, Elena ;
Tresguerres, Jesus A. F. .
EXPERIMENTAL GERONTOLOGY, 2016, 75 :1-7
[19]   Coupling eNOS uncoupling to the innate immune response [J].
Rabelink, Ton J. ;
van Zonneveld, Anton-Jan .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (12) :2585-2587
[20]   Cecal Ligation Puncture Procedure [J].
Toscano, Miguel G. ;
Ganea, Doina ;
Gamero, Ana M. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2011, (51)