Preventive Effects of a Natural Anti-Inflammatory Agent, Astragaloside IV, on Ischemic Acute Kidney Injury in Rats

Shufeng Tan,Guofu Wang,Niansong Wang,Dingkun Gui,Yongping Guo

doi:10.1155/2013/284025

Abstract

This study investigated the anti-inflammatory effects of astragaloside IV(AS-IV) on ischemia/reperfusion (IR) induced acute kidney injury (AKI) in rats. Experimental model of ischemic AKI was induced in rats by bilateral renal artery clamp for 45 min followed by reperfusion of 12 h and 24 h, respectively. AS-IV was orally administered once a day to rats at 10 and 20 mg·kg−1·d−1 for 7 days prior to ischemia. AS-IV pretreatment significantly decreased serum urea, creatinine, and cystatin C levels at 12 h and 24 h of reperfusion in AKI rats. AS-IV pretreatment also ameliorated tubular damage and suppressed the phosphorylation of p65 subunit of NF-κB in AKI rats. Moreover, NF-κB and MPO activity as well as serum and tissue levels of TNF-α, MCP-1, and ICAM-1 were elevated in AKI rats. All of these abnormalities were prevented by AS-IV. Furthermore, AS-IV downregulated the mRNA expression of NF-κB, TNF-α, MCP-1, and ICAM-1 in AKI rats. These results suggest that AS-IV might be developed as a novel therapeutic approach to prevent ischemic AKI through inhibition of NF-κB mediated inflammatory genes expression.

Highlights

Acute kidney injury (AKI) is common in intensive care unit (ICU) and is independently associated with high mortality and morbidity [1,2,3]
Animals were further subdivided into the following groups (n = 8 per subgroup): (1) sham-operated rats pretreated with normal saline (Sham), (2) IR rats pretreated with carboxymethyl cellulose (CMC) vehicle alone served as control (Veh), (3) IR rats pretreated with AS-IV at dose of 10 mg/kg (AL), and (4) IR rats pretreated with AS-IV at dose of 20 mg/kg (AH)
Serum creatinine and blood urea nitrogen (BUN) levels were significantly elevated in vehiclepretreated rats compared with sham-operated animals; AS-IV pretreatment significantly decreased serum creatinine and BUN levels at 12 h (Figures 1(a) and 1(c)) and 24 h (Figures 1(b) and 1(d)) of reperfusion, respectively

Summary

Introduction

Acute kidney injury (AKI) is common in intensive care unit (ICU) and is independently associated with high mortality and morbidity [1,2,3]. Inflammatory response is believed to play a central role in the pathophysiology of ischemic AKI. IR-induced inflammatory responses, including excessive generation of cytokines, overexpression of surface adhesion molecules, and chemotactic proteins, make the inflammatory cells extravasculate from the blood stream and attract to the kidney tissues [5, 6]. The vascular endothelium plays a crucial role in the initiation of inflammatory responses [7]. Numerous studies have demonstrated that ICAM-1 plays an important role in the pathophysiology of AKI [14, 15]. Inflammation is believed to have a central role in the pathogenesis of ischemic AKI

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