Huperzine A attenuates hepatic ischemia reperfusion injury via anti-oxidative and anti-apoptotic pathways

Xu,Zhe; Wang,Yang

doi:10.3892/mmr.2014.2288

Huperzine A attenuates hepatic ischemia reperfusion injury via anti-oxidative and anti-apoptotic pathways

Authors:
- Zhe Xu
- Yang Wang
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Affiliations: Department of Pharmacy, Maanshan Municipal Maternal and Child Health Hospital, Maanshan, Anhui 243011, P.R. China
Published online on: May 30, 2014 https://doi.org/10.3892/mmr.2014.2288
Pages: 701-706

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Abstract

Hepatic ischemia reperfusion (HI/R) injury may occur during liver transplantation and remains a serious concern in clinical practice. Huperzine A (HupA), an alkaloid isolated from the Chinese traditional medicine Huperzia serrata, has been demonstrated to possess anti‑oxidative and anti‑apoptotic properties. In the present study, a rat model of HI/R was established by clamping the hepatic artery, the hepatoportal vein and the bile duct with a vascular clamp for 30 min followed by reperfusion for 6 h under anesthesia. HupA was injected into the tail vein 5 min prior to the induction of HI/R at doses of 167 and 500 µg/kg. The histopathological assessment of the liver was performed using hematoxylin and eosin staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in the serum samples. The tissue levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA) and glutathione (GSH) were also measured spectrophotometrically. Furthermore, the protein expression of caspase‑3, Bcl‑2 and Bax in hepatic tissues was detected via western blot analysis. Treatment of Wistar rats with HupA at doses of 167 and 500 µg/kg markedly attenuated HI/R injury as observed histologically. In addition, the significant reductions of serum ALT and AST were observed in HupA‑treated ischemic rats. Furthermore, HupA treatment enhanced the activity of hepatic tissue SOD, CAT and GSH, but decreased the MDA tissue content. Western blot analysis revealed elevated levels of Bcl‑2 expression but decreased Bax and caspase‑3 tissue expression at the protein level in the HupA‑treated group. The present data suggest that HupA attenuates the HI/R injury of rats through its anti‑oxidative and anti‑apoptotic signaling pathways.

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1	Bayramoglu G, Bayramoglu A, Engur S, Senturk H, Ozturk N and Colak S: The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats. Cytotechnology. Jun 23–2013.(Epub ahead of print).
2	Liu DL, Jeppsson B, Hakansson CH and Odselius R: Multiple-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg. 131:442–447. 1996. View Article : Google Scholar : PubMed/NCBI
3	Çekın AH, Gür G, Türkoğlu S, et al: The protective effect of L-carnitine on hepatic ischemia-reperfusion injury in rats. Turk J Gastroenterol. 24:51–56. 2013.
4	Chan PH: Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res. 29:1943–1949. 2004. View Article : Google Scholar : PubMed/NCBI
5	Chandra J, Samali A and Orrenius S: Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med. 29:323–333. 2000. View Article : Google Scholar : PubMed/NCBI
6	He SQ, Zhang YH, Venugopal SK, et al: Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice. Liver Transpl. 12:1869–1879. 2006. View Article : Google Scholar : PubMed/NCBI
7	Kohli V, Selzner M, Madden JF, Bentley RC and Clavien PA: Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver. Transplantation. 67:1099–1105. 1999. View Article : Google Scholar : PubMed/NCBI
8	Wang R, Yan H and Tang XC: Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin. 27:1–26. 2006. View Article : Google Scholar : PubMed/NCBI
9	Zhang HY, Zheng CY, Yan H, et al: Potential therapeutic targets of huperzine A for Alzheimer’s disease and vascular dementia. Chem Biol Interact. 175:396–402. 2008.PubMed/NCBI
10	Ruan Q, Liu F, Gao Z, et al: The anti-inflamm-aging and hepatoprotective effects of huperzine A in D-galactose-treated rats. Mech Ageing Dev. 134:89–97. 2013. View Article : Google Scholar : PubMed/NCBI
11	Ye W, Gong X, Xie J, et al: AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia/reperfusion. Apoptosis. 15:474–487. 2010. View Article : Google Scholar : PubMed/NCBI
12	Zhang F, Mao Y, Qiao H, et al: Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. Amino Acids. 38:237–245. 2010. View Article : Google Scholar : PubMed/NCBI
13	Jiang H, Meng F, Li W, Tong L, Qiao H and Sun X: Splenectomy ameliorates acute multiple organ damage induced by liver warm ischemia reperfusion in rats. Surgery. 141:32–40. 2007. View Article : Google Scholar : PubMed/NCBI
14	Gillissen A, Bartling A, Schoen S and Schultze-Werninghaus G: Antioxidant function of ambroxol in mononuclear and polymorphonuclear cells in vitro. Lung. 175:235–242. 1997. View Article : Google Scholar : PubMed/NCBI
15	Zhou J, Zhang HY and Tang XC: Huperzine A attenuates cognitive deficits and hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci Lett. 313:137–140. 2001. View Article : Google Scholar : PubMed/NCBI
16	Wang ZF and Tang XC: Huperzine A protects C6 rat glioma cells against oxygen-glucose deprivation-induced injury. FEBS Lett. 581:596–602. 2007. View Article : Google Scholar : PubMed/NCBI
17	Kang KJ: Mechanism of hepatic ischemia/reperfusion injury and protection against reperfusion injury. Transplant Proc. 34:2659–2661. 2002. View Article : Google Scholar : PubMed/NCBI
18	Teoh NC and Farrell GC: Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol. 18:891–902. 2003. View Article : Google Scholar : PubMed/NCBI
19	Schauer RJ, Gerbes AL, Vonier D, et al: Glutathione protects the rat liver against reperfusion injury after prolonged warm ischemia. Ann Surg. 239:220–231. 2004. View Article : Google Scholar : PubMed/NCBI
20	Perry DK, Smyth MJ, Stennicke HR, et al: Zinc is a potent inhibitor of the apoptotic protease, caspase-3. A novel target for zinc in the inhibition of apoptosis. J Biol Chem. 272:18530–18533. 1997. View Article : Google Scholar : PubMed/NCBI
21	Jin S and Dai CL: Attenuation of reperfusion-induced hepatocyte apoptosis is associated with reversed bcl-2/bax ratio in hemi-hepatic artery-preserved portal occlusion. J Surg Res. 174:298–304. 2012. View Article : Google Scholar : PubMed/NCBI