Melatonin Alleviates Contrast-Induced Acute Kidney Injury by Activation of Sirt3.

Chunmei Zhang,Jianmin Yang,Chang Ma,Mengying Suo,Yan Qi,Peili Bu,Jingyuan Li,Chen Zhang,Lin Xie,Lingxin Liu,Xuehui Zheng,Yong Zhou

doi:10.1155/2021/6668887

Abstract

Oxidative stress and apoptosis play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). The purpose of our study was to investigate the protective effects and mechanisms of melatonin against CI-AKI in a CI-AKI mouse model and NRK-52E cells. We established the CI-AKI model in mice, and the animals were pretreated with melatonin (20 mg/kg). Our results demonstrated that melatonin treatment exerted a renoprotective effect by decreasing the level of serum creatinine (SCr) and blood urea nitrogen (BUN), lessening the histological changes of renal tubular injuries, and reducing the expression of neutrophil gelatinase-associated lipid (NGAL), a marker of kidney injury. We also found that pretreatment with melatonin remarkably increased the expression of Sirt3 and decreased the ac-SOD2 K68 level. Consequently, melatonin treatment significantly decreased the oxidative stress by reducing the Nox4, ROS, and malondialdehyde (MDA) content and by increasing the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity levels. The antiapoptotic effect of melatonin on CI-AKI was revealed by decreasing the ratio of Bax/Bcl2 and the cleaved caspase3 level and by reducing the number of apoptosis-positive tubular cells. In addition, melatonin treatment remarkably reduced the inflammatory cytokines of interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and transforming growth factor β (TGFβ) in vivo and in vitro. Sirt3 deletion and specific Sirt3 siRNA abolished the above renoprotective effects of melatonin in mice with iohexol-induced acute kidney injury and in NRK-52E cells. Thus, our results demonstrated that melatonin exhibited the renoprotective effects of antioxidative stress, antiapoptosis, and anti-inflammation by the activation of Sirt3 in the CI-AKI model in vivo and in vitro. Melatonin may be a potential drug to ameliorate CI-AKI in clinical practice.

Highlights

With the increasing prevalence of cardiovascular diseases throughout the world, the use of contrast media (CM) in percutaneous coronary intervention (PCI) has increased as well
To investigate the effect of melatonin on contrast-induced acute kidney injury (CI-acute kidney injury (AKI)), we firstly measured the body weight and kidney weight and found that the ratio of kidney weight to body weight (KW/BW) was significantly decreased in the CM+melatonin group (Mel) group compared to the CM group (Figure 1(a))
These results demonstrated that melatonin played a protective effect against CI-AKI

Summary

Introduction

With the increasing prevalence of cardiovascular diseases throughout the world, the use of contrast media (CM) in percutaneous coronary intervention (PCI) has increased as well. Contrast-induced acute kidney injury (CI-AKI) has become a more common problem in clinical practice and is an important cause of hospital-acquired acute renal insufficiency [1,2,3] despite numerous attempts to reduce the incidence of CI-AKI, such as the improvement of hydration protocols and pretreatment with antioxidants, which are supposed to be less nephrotoxic. Anti-inflammatory, and antiapoptotic properties, melatonin has the ability to protect against diseases. Published studies have elucidated that melatonin can contribute to the improvement of cardiac function in diabetic cardiomyopathy (DCM) [8, 9]. Recent studies have focused on the role of melatonin in the treatment of myocardial ischemia/reperfusion (MI/R) injury [10]. The underlying mechanisms of how melatonin protects against CI-AKI remain poorly understood

Objectives

Methods

Results

Conclusion