Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway

Liu Tongqiang,Liu Shaopeng,Zhang Ting,Song Nana,Hu Jiachang,Yu Xiaofang,Xu Xialian,Ding Xiaoqiang

doi:10.1155/2016/7079487

Abstract

Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway.

Highlights

Contrast-induced acute renal injury (CI-AKI) is an important syndrome of acute renal failure occurring after the intravascular administration of radiographic contrast media (CM) in diagnostic and interventional procedures, which is defined as an increase of 25% or more or an absolute increase of 0.5 mg/dL or more in serum creatinine (Scr) from baseline value within 3 days after exposure to CM in the absence of any alternative causes [1]
Our results suggest that Salvianolic acid B (SB) prevents Contrast-induced acute kidney injury (CI-AKI) by reducing oxidative stress through the PI3K/Akt/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway
The levels of Scr and blood urea nitrogen (BUN) in the SB + CM group were markedly decreased compared with the CM group

Summary

Introduction

Contrast-induced acute renal injury (CI-AKI) is an important syndrome of acute renal failure occurring after the intravascular administration of radiographic contrast media (CM) in diagnostic and interventional procedures, which is defined as an increase of 25% or more or an absolute increase of 0.5 mg/dL or more in serum creatinine (Scr) from baseline value within 3 days after exposure to CM in the absence of any alternative causes [1]. CI-AKI is the third most common cause of acute renal failure in hospitalized patients [2] and is associated with replacement therapy, prolonged hospitalization, increased medical cost, and increased mortality [3, 4]. Antioxidant-mediated protection of renal function with specific drugs provides indirect evidence that oxidative stress is considered to be involved in the pathogenesis of CIAKI [6, 7]. It was reported that SB activated the PI3K/Akt signaling pathway [11] and induced nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and glutamate-l-cysteine ligase catalytic subunit (GCLC) expression, thereby protecting against APAP-induced liver injury and protecting dopaminergic neurons by an Nrf2-mediated action [9, 12]. Activation of the PI3K/Akt/Nrf pathway could protect against cell and organ injury through upregulation of antioxidant enzyme and phase II detoxification enzyme

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