Protective effects of gastrodin pretreatment on mouse hepatic ischemia‑reperfusion occurring through antioxidant and anti‑apoptotic mechanisms

Sun,Bo; Jiang,Jie; Zhu,Xinyan; Yang,Dan; Cui,Zhenyu; Zhang,Yu; Zhang,Minbo; Qian,Yiting; Liu,Ruilin; Yang,Wenzhuo

doi:10.3892/etm.2021.9902

Protective effects of gastrodin pretreatment on mouse hepatic ischemia‑reperfusion occurring through antioxidant and anti‑apoptotic mechanisms

Authors:
- Bo Sun
- Jie Jiang
- Xinyan Zhu
- Dan Yang
- Zhenyu Cui
- Yu Zhang
- Minbo Zhang
- Yiting Qian
- Ruilin Liu
- Wenzhuo Yang
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Affiliations: Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China, Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R. China
Published online on: March 8, 2021 https://doi.org/10.3892/etm.2021.9902
Article Number: 471

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Abstract

Hepatic ischemia‑reperfusion injury (HIRI) often occurs following surgical procedures such as liver resection and transplantation. However, despite its clinical prominence, to the best of our knowledge, there remain no effective strategies to treat HIRI. Therefore, the aim of present study was to identify therapeutic agents that can exert beneficial effects against HIRI. The present study found that following hepatic IR modeling in mice, gastrodin (Gas) pretreatment improved the IR outcomes in terms of the serum biochemical indexes (alanine transaminase and aspartate transaminase), tissue biochemical indexes (superoxide dismutase, malondialdehyde and reduced glutathione content) and tissue pathology (H&E staining). In addition, compared with those in the IR + vehicle group, the IR + Gas group showed upregulated expression levels of nuclear erythroid 2‑related factor 2, heme oxygenase 1 and Bcl‑2 as detected by western blotting and reverse transcription‑quantitative PCR. The mRNA and protein expression levels of Bax and caspase‑3 were downregulated in the IR + Gas group compared with the IR + vehicle group. Concurrently, no significant differences were observed in the parameters between the Sham + vehicle and the Sham + Gas groups, indicating that Gas pretreatment may not cause liver damage. In conclusion, the findings of the present study revealed that Gas pretreatment exerted a protective effect in HIRI through both antioxidant and anti‑apoptotic mechanisms.

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1	Dery KJ, Nakamura K, Kadono K, Hirao H, Kageyama S, Ito T, Kojima H, Kaldas FM, Busuttil RW and Kupiec-Weglinski JW: Human Antigen R (HuR): A new regulator of heme oxygenase-1 cytoprotection in mouse and human liver transplant injury. Hepatology. 72:1056–1072. 2019.PubMed/NCBI View Article : Google Scholar
2	Covington SM, Bauler LD and Toledo-Pereyra LH: Akt: A therapeutic target in hepatic ischemia-reperfusion injury. J Invest Surg. 30:47–55. 2017.PubMed/NCBI View Article : Google Scholar
3	Peralta C, Jimenez-Castro MB and Gracia-Sancho J: Hepatic ischemia and reperfusion injury: Effects on the liver sinusoidal milieu. J Hepatol. 59:1094–1106. 2013.PubMed/NCBI View Article : Google Scholar
4	Han X, Shi H, Liu K, Zhong L, Wang F and You Q: Protective effect of gastrodin on myocardial ischemia-reperfusion injury and the expression of Bax and Bcl-2. Exp Ther Med. 17:4389–4394. 2019.PubMed/NCBI View Article : Google Scholar
5	Ju C, Colgan SP and Eltzschig HK: Hypoxia-inducible factors as molecular targets for liver diseases. J Mol Med (Berl). 94:613–627. 2016.PubMed/NCBI View Article : Google Scholar
6	Qiu M, Xiao F, Wang T, Piao S, Zhao W, Shao S, Yan M and Zhao D: Protective effect of Hedansanqi Tiaozhi Tang against non-alcoholic fatty liver disease in vitro and in vivo through activating Nrf2/HO-1 antioxidant signaling pathway. Phytomedicine. 67(153140)2019.PubMed/NCBI View Article : Google Scholar
7	Theruvath TP, Czerny C, Ramshesh VK, Zhong Z, Chavin KD and Lemasters JJ: C-Jun N-terminal kinase 2 promotes graft injury via the mitochondrial permeability transition after mouse liver transplantation. Am J Transplant. 8:1819–1828. 2008.PubMed/NCBI View Article : Google Scholar
8	Matias M, Silvestre S, Falcao A and Alves G: Gastrodia elata and epilepsy: Rationale and therapeutic potential. Phytomedicine. 23:1511–1526. 2016.PubMed/NCBI View Article : Google Scholar
9	Li JJ, Liu SJ, Liu XY and Ling EA: Herbal compounds with special reference to gastrodin as potential therapeutic agents for microglia mediated neuroinflammation. Curr Med Chem. 25:5958–5974. 2018.PubMed/NCBI View Article : Google Scholar
10	Hu Y, Li C and Shen W: Gastrodin alleviates memory deficits and reduces neuropathology in a mouse model of Alzheimer's disease. Neuropathology. 34:370–377. 2014.PubMed/NCBI View Article : Google Scholar
11	Matsumata T, Kanematsu T, Shirabe K, Yamagata M, Utsunomiya T, Furuta T and Sugimachi K: Modified technique of pringle's maneuver in resection of the liver. Surg Gynecol Obstet. 172:245–246. 1991.PubMed/NCBI
12	Li Y, Li T and Qi H: Protective effect of minocycline on hepatic ischemia-reperfusion injury in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 39:1137–1144. 2014.PubMed/NCBI View Article : Google Scholar : (In Chinese).
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
14	Smedsrød B, De Bleser PJ, Braet F, Lovisetti P, Vanderkerken K, Wisse E and Geerts A: Cell biology of liver endothelial and Kupffer cells. Gut. 35:1509–1516. 1994.PubMed/NCBI View Article : Google Scholar
15	Kaplowitz N: Drug-induced liver injury. Clin Infect Dis. 38 (Suppl 2):S44–S48. 2004.PubMed/NCBI View Article : Google Scholar
16	Senoner T, Schindler S, Stattner S, Ofner D, Troppmair J and Primavesi F: Associations of oxidative stress and postoperative outcome in liver surgery with an outlook to future potential therapeutic options. Oxid Med Cell Longev. 2019(3950818)2019.PubMed/NCBI View Article : Google Scholar
17	Yang P, Han Y, Gui L, Sun J, Chen YL, Song R, Guo JZ, Xie YN, Lu D and Sun L: Gastrodin attenuation of the inflammatory response in H9c2 cardiomyocytes involves inhibition of NF-κB and MAPKs activation via the phosphatidylinositol 3-kinase signaling. Biochem Pharmacol. 85:1124–1133. 2013.PubMed/NCBI View Article : Google Scholar
18	Chen Pz, Jiang Hh, Wen B, Ren SC, Chen Y, Ji WG, Hu B, Zhang J, Xu F and Zhu ZR: Gastrodin suppresses the amyloid β-induced increase of spontaneous discharge in the entorhinal cortex of rats. Neural Plast. 2014(320937)2014.PubMed/NCBI View Article : Google Scholar
19	Zhan HD, Zhou HY, Sui YP, Du XL, Wang WH, Dai L, Sui F, Huo HR and Jiang TL: The rhizome of Gastrodia elata Blume-An ethnopharmacological review. J Ethnopharmacol. 189:361–385. 2016.PubMed/NCBI View Article : Google Scholar
20	Qu LL, Yu B, Li Z, Jiang WX, Jiang JD and Kong WJ: Gastrodin ameliorates oxidative stress and proinflammatory response in nonalcoholic fatty liver disease through the AMPK/Nrf2 pathway. Phytother Res. 30:402–411. 2016.PubMed/NCBI View Article : Google Scholar
21	Dai JN, Zong Y, Zhong LM, Li YM, Zhang W, Bian LG, Ai QL, Liu YD, Sun J and Lu D: Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS One. 6(e21891)2011.PubMed/NCBI View Article : Google Scholar
22	Peng Z, Wang S, Chen G, Cai M, Liu R, Deng J, Liu J, Zhang T, Tan Q and Hai C: Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway. Neurochem Res. 40:661–673. 2015.PubMed/NCBI View Article : Google Scholar
23	Masuda Y, Vaziri ND, Takasu C, Li S, Robles L, Pham C, Le A, Vo K, Farzaneh SH, Stamos MJ and Ichii H: Salutary effect of pre-treatment with an Nrf2 inducer on ischemia reperfusion injury in the rat liver. Gastroenterol Hepatol (Que). 1:1–7. 2014.PubMed/NCBI View Article : Google Scholar
24	Chen Z, Zhong H, Wei J, Lin S, Zong Z, Gong F, Huang X, Sun J, Li P, Lin H, et al: Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis. Arthritis Res Ther. 21(300)2019.PubMed/NCBI View Article : Google Scholar
25	Tanaka Y, Maher JM, Chen C and Klaassen CD: Hepatic ischemia-reperfusion induces renal heme oxygenase-1 via NF-E2-related factor 2 in rats and mice. Mol Pharmacol. 71:817–825. 2007.PubMed/NCBI View Article : Google Scholar
26	Bauer M and Bauer I: Heme oxygenase-1: Redox regulation and role in the hepatic response to oxidative stress. Antioxid Redox Signal. 4:749–758. 2002.PubMed/NCBI View Article : Google Scholar
27	Schwabe RF and Luedde T: Apoptosis and necroptosis in the liver: A matter of life and death. Nat Rev Gastroenterol Hepatol. 15:738–752. 2018.PubMed/NCBI View Article : Google Scholar
28	Lei K and Davis RJ: JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA. 100:2432–2437. 2003.PubMed/NCBI View Article : Google Scholar
29	Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA and Davis RJ: Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science. 288:870–874. 2000.PubMed/NCBI View Article : Google Scholar
30	Liu Q, Rehman H, Krishnasamy Y, Schnellmann RG, Lemasters JJ and Zhong Z: Improvement of liver injury and survival by JNK2 and iNOS deficiency in liver transplants from cardiac death mice. J Hepatol. 63:68–74. 2015.PubMed/NCBI View Article : Google Scholar
31	Shalini S, Dorstyn L, Dawar S and Kumar S: Old, new and emerging functions of caspases. Cell Death Differ. 22:526–539. 2015.PubMed/NCBI View Article : Google Scholar
32	Lossi L, Castagna C and Merighi A: Caspase-3 mediated cell death in the normal development of the mammalian cerebellum. Int J Mol Sci. 19(3999)2018.PubMed/NCBI View Article : Google Scholar