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.

Highlights

  • Sepsis is considered as a complicated chain of systemic reactions in response to the imbalance between the host immune response and the pathogenic microorganism, causing septic shock and multiple organ dysfunction (Gustot, 2011)

  • These results indicated that melatonin could reduce renal injury by inhibiting the production of reactive oxygen species (ROS)

  • This study found that melatonin can play a protective role in Acute kidney injury (AKI) caused by sepsis

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Summary

Introduction

Sepsis is considered as a complicated chain of systemic reactions in response to the imbalance between the host immune response and the pathogenic microorganism, causing septic shock and multiple organ dysfunction (Gustot, 2011). Acute kidney injury (AKI) is a common complication that accounts for death in patients with sepsis, and the incidence of AKI is increasing year by year. The morbidity of AKI in community hospitals is as low as 2%, whereas in large medical institutions, rates can be more than 20% of all hospitalizations (Bellomo et al, 2012). AKI is an independent prognostic risk factor for septic patients. The previous studies revealed that the prevention of MMP (matrix metalloproteinase) activation may be beneficial for the prevention of kidney injury (Gonsalez et al, 2019). Previous study has shown that the modulation of oxidative stress affects AKI (Aksu et al, 2011). There is still no effective pharmacological intervention to treat or reverse AKI

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