Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Wang,Kun-Peng; Bai,Yu; Wang,Jian; Zhang,Jin-Zhen

doi:10.3892/mmr.2014.2004

Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Authors:
- Kun-Peng Wang
- Yu Bai
- Jian Wang
- Jin-Zhen Zhang
View Affiliations

Affiliations: Department of Anesthesiology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Anesthesiology, Shenzhen Hospital, Shenzhen, Guangdong 518000, P.R. China
Published online on: March 4, 2014 https://doi.org/10.3892/mmr.2014.2004
Pages: 1813-1819

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Schisandra chinensis is a well-known traditional medicinal herb. Acetaminophen is a commonly used over‑the‑counter analgesic and overdose of acetaminophen was the most frequent cause of acute liver failure. However, no studies have demonstrated the role of Schisandra chinensis in acetaminophen-induced acute liver failure to the best of our knowledge. In this study, an acute liver injury model was established in mice using acetaminophen. The protective role of Schisandra chinensis was detected by histopathological analysis, and measurement of the serum transaminase levels and hepatic Cyp activity levels in the mouse model. Subsequently, hepatocytes were isolated from the livers of the mouse model. The cell cycle, apoptosis, mitochondrial membrane potential and reactive oxygen species were determined using flow cytometry. Cell proliferation and 26S proteasome activity were determined using spectrophotometry. Schisandra chinensis was found to resist acetaminophen-induced hepatotoxicity by protecting mitochondria and lysosomes and inhibiting the phosphor-c-Jun N‑terminal kinase signaling pathway. These findings provide a novel application of Schisandra chinensis against acetaminophen-induced acute liver failure.

View Figures

View References

1	Fontana RJ: Acute liver failure including acetaminophen overdose. Med Clin North Am. 92:761–794. 2008. View Article : Google Scholar : PubMed/NCBI
2	Moyer AM, Fridley BL, Jenkins GD, et al: Acetaminophen-NAPQI hepatotoxicity: a cell line model system genome-wide association study. Toxicol Sci. 120:33–41. 2011. View Article : Google Scholar : PubMed/NCBI
3	Daly FF, Fountain JS, Murray L, Graudins A and Buckley NA; Panel of Australian and New Zealand clinical toxicologists. Guidelines for the management of paracetamol poisoning in Australia and New Zealand - explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust. 188:296–301. 2008.
4	James LP, Gill P and Simpson P: Predicting risk in patients with acetaminophen overdose. Expert Rev Gastroenterol Hepatol. 7:509–512. 2013. View Article : Google Scholar : PubMed/NCBI
5	Panossian A and Wikman G: Pharmacology of Schisandra chinensis Bail.: an overview of Russian research and uses in medicine. J Ethnopharmacol. 118:183–212. 2008.
6	Hancke JL, Burgos RA and Ahumada F: Schisandra chinensis (Turcz.) Baill. Fitoterapia. 70:451–471. 1999. View Article : Google Scholar
7	Chen DF, Zhang SX, Xie L, et al: Anti-AIDS agents-XXVI. Structure-activity correlations of gomisin-G-related anti-HIV lignans from Kadsura interior and of related synthetic analogues. Bioorg Med Chem. 5:1715–1723. 1997. View Article : Google Scholar : PubMed/NCBI
8	Chiu PY, Mak DH, Poon MK and Ko KM: In vivo antioxidant action of a lignan-enriched extract of Schisandra fruit and an anthraquinone-containing extract of Polygonum root in comparison with schisandrin B and emodin. Planta Med. 68:951–956. 2002.PubMed/NCBI
9	Ram VJ: Herbal preparations as a source of hepatoprotective agents. Drug News Perspect. 14:353–363. 2001.PubMed/NCBI
10	Turk B and Turk V: Lysosomes as ‘suicide bags’ in cell death: myth or reality? J Biol Chem. 284:21783–21787. 2009.
11	Szopa A and Ekiert H: In vitro cultures of Schisandra chinensis (Turcz.) Baill (Chinese magnolia vine) - a potential biotechnological rich source of therapeutically important phenolic acids. Appl Biochem Biotechnol. 166:1941–1948. 2012.
12	Kurz T, Terman A and Brunk UT: Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys. 462:220–230. 2007. View Article : Google Scholar : PubMed/NCBI
13	Uchiyama A, Kim JS, Kon K, Jaeschke H, Ikejima K, Watanabe S and Lemasters JJ: Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress-induced hepatocellular injury. Hepatology. 48:1644–1654. 2008. View Article : Google Scholar : PubMed/NCBI
14	Boya P and Kroemer G: Lysosomal membrane permeabilization in cell death. Oncogene. 27:6434–6451. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kon K, Kim JS, Uchiyama A, Jaeschke H and Lemasters JJ: Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes. Toxicol Sci. 117:101–108. 2010. View Article : Google Scholar : PubMed/NCBI
16	Jaeschke H and Bajt ML: Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol Sci. 89:31–41. 2006. View Article : Google Scholar : PubMed/NCBI
17	Gardner CR, Hankey P, Mishin V, Francis M, Yu S, Laskin JD and Laskin DL: Regulation of alternative macrophage activation in the liver following acetaminophen intoxication by stem cell-derived tyrosine kinase. Toxicol Appl Pharmacol. 262:139–148. 2012. View Article : Google Scholar : PubMed/NCBI
18	Qian T, Nieminen AL, Herman B and Lemasters JJ: Mitochondrial permeability transition in pH-dependent reperfusion injury to rat hepatocytes. Am J Physiol. 273:C1783–C1792. 1997.PubMed/NCBI
19	Fekete MR, McBride WH and Pajonk F: Anthracyclines, proteasome activity and multi-drug-resistance. BMC Cancer. 5:1142005. View Article : Google Scholar : PubMed/NCBI
20	Larson AM, Polson J, Fontana RJ, et al: Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 42:1364–1372. 2005. View Article : Google Scholar : PubMed/NCBI
21	Ostapowicz G, Fontana RJ, Schiødt FV, et al; U.S. Acute Liver Failure Study Group. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 137:947–954. 2002. View Article : Google Scholar : PubMed/NCBI
22	Jaeschke H: Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol. J Pharmacol Exp Ther. 255:935–941. 1990.
23	Chiu H, Gardner CR, Dambach DM, Brittingham JA, Durham SK, Laskin JD and Laskin DL: Role of p55 tumor necrosis factor receptor 1 in acetaminophen-induced antioxidant defense. Am J Physiol Gastrointest Liver Physiol. 285:G959–G966. 2003.PubMed/NCBI
24	Gardner CR, Gray JP, Joseph LB, et al: Potential role of caveolin-1 in acetaminophen-induced hepatotoxicity. Toxicol Appl Pharmacol. 245:36–46. 2010. View Article : Google Scholar : PubMed/NCBI
25	Hu D, Cao Y, He R, Han N, Liu Z, Miao L and Yin J: Schizandrin, an antioxidant lignan from Schisandra chinensis, ameliorates Aβ1–42-induced memory impairment in mice. Oxid Med Cell Longev. 2012:7217212012.PubMed/NCBI
26	Das J, Ghosh J, Manna P and Sil PC: Acetaminophen induced acute liver failure via oxidative stress and JNK activation: protective role of taurine by the suppression of cytochrome P450 2E1. Free Radic Res. 44:340–355. 2010. View Article : Google Scholar : PubMed/NCBI
27	Gonzalez FJ: Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1. Mutat Res. 569:101–110. 2005. View Article : Google Scholar : PubMed/NCBI
28	Gunawan BK, Liu ZX, Han D, Hanawa N, Gaarde WA and Kaplowitz N: c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity. Gastroenterology. 131:165–178. 2006. View Article : Google Scholar : PubMed/NCBI
29	Hanawa N, Shinohara M, Saberi B, Gaarde WA, Han D and Kaplowitz N: Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. J Biol Chem. 283:13565–13577. 2008. View Article : Google Scholar : PubMed/NCBI