Abstract:

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-1α, Il-1β, Mcp-1, and Tgf-β1. 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.

Keywords: ROS (reactive oxygen species); acute kidney injury; melatonin; renal dysfunction; sepsis.

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Melatonin Alleviates Renal Injury in Mouse Model of Sepsis

^{Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China}

^{The Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China}

^{Hubei Key Laboratory of Diabetes and Angiopathy, Hubei University of Science and Technology, Xianning, China}

Edited by:Paula Gomes, University of Porto, Portugal

Reviewed by:Vittorio Calabrese, University of Catania, Italy

Jorge G. Farias, University of La Frontera, Chile

*Correspondence: Qiulun Lu, nc.ude.umjn@ulnuluiQ; Chao Liu, nc.ude.tsubh@oahcuil

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology

^{These authors have contributed equally to this work}

Edited by:Paula Gomes, University of Porto, PortugalReviewed by:Vittorio Calabrese, University of Catania, Italy

Jorge G. Farias, University of La Frontera, Chile

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology

Received 2021 Apr 20; Accepted 2021 Aug 5.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

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-1α, Il-1β, Mcp-1, and Tgf-β1. 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.

Keywords: melatonin, sepsis, ROS (reactive oxygen species), acute kidney injury, renal dysfunction

Abstract

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