Glycyrrhizin protects mice against renal ischemia-reperfusion injury through inhibition of apoptosis and inflammation by downregulating p38 mitogen-activated protein kinase signaling.

Shaojun Ye,Xingguo She,Yingzi Ming,Yi Zhu,Hong Liu,Qifa Ye

doi:10.3892/etm.2014.1570

Abstract

Ischemia-reperfusion (I/R) often leads to acute kidney injury, chronic renal failure and kidney transplantation failure. Glycyrrhizin is extracted from Glycyrrhiza glabra roots and is the predominant active component, which exhibits anti-inflammatory effects. However, to the best of our knowledge, the effect of glycyrrhizin on I/R-induced renal injury has not been investigated. In the present study, glycyrrhizin was demonstrated to attenuate renal I/R injury in mice via administration of glycyrrhizin, which suppressed the serum levels of creatinine and blood urea nitrogen 6 h following reperfusion; furthermore, the superoxide anions as well as the activity of superoxide dismutase within renal tissues was reduced by glycyrrhizin pretreatment. Moreover, the protein level of cleaved caspase-3, as well as its activity in renal tissue, was suppressed as a result of the glycyrrhizin pretreatment, indicating that glycyrrhizin inhibits I/R-induced renal cell apoptosis. In addition, glycyrrhizin pretreatment appeared to ameliorate I/R-induced renal injury via inhibition of inflammatory cell infiltration, as well as the production of pro-inflammatory cytokines, including tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β and IL-6. The underlying molecular mechanism was investigated and it was shown that the activity of p38 mitogen-activated protein kinase signaling was downregulated as a result of glycyrrhizin administration. In conclusion, the present study indicated that glycyrrhizin provided significant protection against I/R-induced renal injury in mice by inhibiting inflammatory responses and renal cell apoptosis. Therefore, glycyrrhizin may be used in abdominal surgery and kidney transplantation for the prevention of renal I/R damage.

Highlights

Ischemia‐reperfusion (I/R)‐induced kidney injury results from a sudden transient reduction in blood flow, arising from shock, trauma, abdominal surgery or kidney transplantation, and often leads to acute kidney injury, chronic renal failure or failure of the kidney transplant [1,2,3]
The superoxide anion (SOA) level that was observed in the soluble fraction of the renal tissue 6 h after reperfusion was significantly higher in the saline‐treated control group, when compared with that observed in the sham‐operated and glycyrrhizin‐treated groups (Fig. 1C)
To the best of our knowledge, this is the first study to show that pretreatment with glycyrrhizin attenuates renal I/R injury via inhibition of tissue inflammation as well as protection against cell apoptosis, indicating that glycyrrhizin may be used for the prevention of I/R‐induced kidney injury in clinical settings

Summary

Introduction

Ischemia‐reperfusion (I/R)‐induced kidney injury results from a sudden transient reduction in blood flow, arising from shock, trauma, abdominal surgery or kidney transplantation, and often leads to acute kidney injury, chronic renal failure or failure of the kidney transplant [1,2,3]. Previous studies have identified that I/R leads to the activation and infiltration of neutrophils and macrophages, which release numerous pro‐inflammatory mediators that trigger acute inflammatory responses; this has been demonstrated to be crucial in I/R‐induced renal injury [4,5,6,7]. Renal cell apoptosis may be involved in I/R‐induced renal injury. Glycyrrhizin is the predominant active component that is extracted from the roots of Glycyrrhiza glabra and exhibits anti‐inflammatory effects [8]. Glycyrrhizin has been reported to attenuate I/R‐induced gut, spinal cord, liver and heart damage [9,10,11,12,13,14]. To the best of our knowledge, the effect of glycyrrhizin on I/R‐induced renal injury has not been investigated

Methods

Results

Conclusion