Glycyrrhizin protects mice against renal ischemia‑reperfusion injury through inhibition of apoptosis and inflammation by downregulating p38 mitogen‑activated protein kinase signaling Retraction in /10.3892/etm.2023.12223

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

doi:10.3892/etm.2014.1570

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

Retraction in: /10.3892/etm.2023.12223

Authors:
- Shaojun Ye
- Yi Zhu
- Yingzi Ming
- Xingguo She
- Hong Liu
- Qifa Ye
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Affiliations: Research Center of the Chinese Health Ministry on Transplantation Medicine Engineering and Technology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: February 21, 2014 https://doi.org/10.3892/etm.2014.1570
Pages: 1247-1252

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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.

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1	Arumugam TV, Shiels IA, Woodruff TM, Granger DN and Taylor SM: The role of the complement system in ischemia-reperfusion injury. Shock. 21:401–409. 2004. View Article : Google Scholar : PubMed/NCBI
2	Ichimaru N, Yazawa K and Takahara S: Kidney transplantation: how shall we deal with marginal cases? Future prospects from basic research. Hinyokika Kiyo. 56:481–484. 2010.(In Japanese).
3	Versteilen AM, Di Maggio F, Leemreis JR, Groeneveld AB, Musters RJ and Sipkema P: Molecular mechanisms of acute renal failure following ischemia/reperfusion. Int J Artif Organs. 27:1019–1029. 2004.PubMed/NCBI
4	Jin R, Yang G and Li G: Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 87:779–789. 2010. View Article : Google Scholar : PubMed/NCBI
5	Kupiec-Weglinski JW and Busuttil RW: Ischemia and reperfusion injury in liver transplantation. Transplant Proc. 37:1653–1656. 2005. View Article : Google Scholar : PubMed/NCBI
6	De Greef KE, Ysebaert DK, Ghielli M, et al: Neutrophils and acute ischemia-reperfusion injury. J Nephrol. 11:110–122. 1998.PubMed/NCBI
7	Thurman JM: Triggers of inflammation after renal ischemia/reperfusion. Clin Immunol. 123:7–13. 2007. View Article : Google Scholar : PubMed/NCBI
8	Okda FA, Yassein S, Ahmed AR, Soufy H and Nasr SM: Some haematological and biochemical investigations on duck virus hepatitis following administration of glycyrrhizin. ISRN Pharmacol. 2013:8494122013.PubMed/NCBI
9	Di Paola R, Menegazzi M, Mazzon E, et al: Protective effects of glycyrrhizin in a gut hypoxia (ischemia)-reoxygenation (reperfusion) model. Intensive Care Med. 35:687–697. 2009.PubMed/NCBI
10	Mabuchi A, Wake K, Marlini M, Watanabe H and Wheatley AM: Protection by glycyrrhizin against warm ischemia-reperfusion-induced cellular injury and derangement of the microcirculatory blood flow in the rat liver. Microcirculation. 16:364–376. 2009. View Article : Google Scholar : PubMed/NCBI
11	Liu L, Zhou HY, Ran K and Wang JB: Glycyrrhiznatis ameliorates rabbit myocardial ischemia-reperfusion injury through P38MAPK pathway. Nan Fang Yi Ke Da Xue Xue Bao. 30:298–300. 2010.(In Chinese).
12	Ogiku M, Kono H, Hara M, Tsuchiya M and Fujii H: Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion in rats. J Pharmacol Exp Ther. 339:93–98. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhai CL, Zhang MQ, Zhang Y, et al: Glycyrrhizin protects rat heart against ischemia-reperfusion injury through blockade of HMGB1-dependent phospho-JNK/Bax pathway. Acta Pharmacol Sin. 33:1477–1487. 2012. View Article : Google Scholar : PubMed/NCBI
14	Ni B, Cao Z and Liu Y: Glycyrrhizin protects spinal cord and reduces inflammation in spinal cord ischemia-reperfusion injury. Int J Neurosci. 123:745–751. 2013. View Article : Google Scholar : PubMed/NCBI
15	Fang F, Liu GC, Zhou X, et al: Loss of ACE2 exacerbates murine renal ischemia-reperfusion injury. PLoS One. 8:e714332013. View Article : Google Scholar : PubMed/NCBI
16	Amura CR, Renner B, Lyubchenko T, Faubel S, Simonian PL and Thurman JM: Complement activation and toll-like receptor-2 signaling contribute to cytokine production after renal ischemia/reperfusion. Mol Immunol. 52:249–257. 2012. View Article : Google Scholar : PubMed/NCBI
17	Wang YP, Li G, Ma LL, et al: Penehyclidine hydrochloride ameliorates renal ischemia-reperfusion injury in rats. J Surg Res. 186:390–397. 2014. View Article : Google Scholar : PubMed/NCBI
18	McIlwain DR, Berger T and Mak TW: Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 5:a0086562013. View Article : Google Scholar : PubMed/NCBI
19	Zhang A, Fu S, Chen L, et al: Lacidipine attenuates apoptosis via a caspase-3 dependent pathway in human kidney cells. Cell Physiol Biochem. 32:1040–1049. 2013. View Article : Google Scholar : PubMed/NCBI
20	Daemen MA, de Vries B and Buurman WA: Apoptosis and inflammation in renal reperfusion injury. Transplantation. 73:1693–1700. 2002. View Article : Google Scholar : PubMed/NCBI
21	Zhou X, Luo YC, Ji WJ, et al: Modulation of mononuclear phagocyte inflammatory response by liposome-encapsulated voltage gated sodium channel inhibitor ameliorates myocardial ischemia/reperfusion injury in rats. PLoS One. 8:e743902013. View Article : Google Scholar
22	Ysebaert DK, De Greef KE, Vercauteren SR, et al: Identification and kinetics of leukocytes after severe ischaemia/reperfusion renal injury. Nephrol Dial Transplant. 15:1562–1574. 2000. View Article : Google Scholar : PubMed/NCBI
23	Facio FN Jr, Sena AA, Araújo LP, et al: Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats. J Mol Med (Berl). 89:51–63. 2011. View Article : Google Scholar : PubMed/NCBI
24	Bolisetty S and Agarwal A: Neutrophils in acute kidney injury: not neutral any more. Kidney Int. 75:674–676. 2009. View Article : Google Scholar : PubMed/NCBI
25	Jing XX, Wang ZG, Ran HT, et al: Evaluation of renal ischemia-reperfusion injury in rabbits using microbubbles targeted to activated neutrophils. Clin Imaging. 32:178–182. 2008. View Article : Google Scholar : PubMed/NCBI
26	Zhang S, Qi Y, Xu Y, et al: Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral ischemia-reperfusion injury through suppression of apoptosis and inflammation. Neurochem Int. 63:522–532. 2013.PubMed/NCBI
27	Lai EW, Toledo-Pereyra LH, Walsh J, Lopez-Neblina F and Anaya-Prado R: The role of MAP kinases in trauma and ischemia-reperfusion. J Invest Surg. 17:45–53. 2004. View Article : Google Scholar : PubMed/NCBI
28	Khan M, Varadharaj S, Ganesan LP, et al: C-phycocyanin protects against ischemia-reperfusion injury of heart through involvement of p38 MAPK and ERK signaling. Am J Physiol Heart Circ Physiol. 290:H2136–H2145. 2006. View Article : Google Scholar : PubMed/NCBI