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Irish Journal of Medical Science (1971 -)
Published in: Irish Journal of Medical Science (1971 -) 1/2016

01-02-2016 | Original Article

Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation-mediated effect?

Authors: B. Li, L. Wang, Q. Lu, W. Da

Published in: Irish Journal of Medical Science (1971 -) | Issue 1/2016

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Abstract

Aim

Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin.

Methods

Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague–Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks.

Results

Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin.

Conclusions

Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.
Literature
1.
Vernon G, Baranova A, Younossi ZM (2011) Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34(3):274–285PubMedCrossRef
2.
Pinzani M (2011) Pathophysiology of non-alcoholic steatohepatitis and basis for treatment. Dig Dis 29(2):243–248PubMedCrossRef
3.
Greenfield V, Cheung O, Sanyal AJ (2008) Recent advances in nonalcoholic fatty liver disease. Curr Opin Gastroenterol 24(3):320–327PubMedCrossRef
4.
Xu W, Shao L, Zhou C, Wang H, Guo J (2011) Upregulation of Nrf2 expression in non-alcoholic fatty liver and steatohepatitis. Hepatogastroenterology 58(112):2077–2080PubMedCrossRef
5.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H (2007) Curcumin: the Indian solid gold. Adv Exp Med Biol 595:1–75PubMedCrossRef
6.
Carmona-Ramírez I, Santamaría A, Tobón-Velasco JC et al (2013) Curcumin restores Nrf2 levels and prevents quinolinic acid-induced neurotoxicity. J Nutr Biochem 24(1):14–24PubMedCrossRef
7.
Charoensuk L, Pinlaor P, Prakobwong S et al (2011) Curcumin induces a nuclear factor-erythroid 2-related factor 2-driven response against oxidative and nitrative stress after praziquantel treatment in liver fluke-infected hamsters. Int J Parasitol 41(6):615–626PubMedCrossRef
8.
Shehzad A, Ha T, Subhan F, Lee YS (2011) New mechanisms and the anti-inflammatory role of curcumin in obesity and obesity-related metabolic diseases. Eur J Nutr 50(3):151–161PubMedCrossRef
9.
Jurenka JS (2009) Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 14(2):141–153PubMed
10.
Vera-Ramirez L, Pérez-Lopez P, Varela-Lopez A et al (2013) Curcumin and liver disease. BioFactors 39(1):88–100PubMedCrossRef
11.
Zingg JM, Hasan ST, Meydani M (2013) Molecular mechanisms of hypolipidemic effects of curcumin. BioFactors 39(1):101–121PubMedCrossRef
12.
García-Niño WR, Pedraza-Chaverrí J (2014) Protective effect of curcumin against heavy metals-induced liver damage. Food Chem Toxicol 69:182–201PubMedCrossRef
13.
Mlinar B, Marc J, Janez A, Pfeifer M (2007) Molecular mechanisms of insulin resistance and associated diseases. Clin Chim Acta 375(1–2):20–35PubMedCrossRef
14.
Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR (1999) Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 94(9):2467–2474PubMedCrossRef
15.
Singh S, Aggarwal BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem 270(42):24995–25000PubMedCrossRef
16.
Neuschwander-Tetri BA, Clark JM, Bass NM, NASH Clinical Research Network et al (2010) Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 52(3):913–924PubMedPubMedCentralCrossRef
17.
Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C (2008) Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med 14(2):72–81PubMedCrossRef
18.
Wieckowska A, Papouchado BG, Li Z et al (2008) Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol 103(6):1372–1379PubMedCrossRef
19.
Lin FL, Hsu JL, Chou CH et al (2011) Activation of p38 MAPK by damnacanthal mediates apoptosis in SKHep 1 cells through the DR5/TRAIL and TNFR1/TNF-α and p53 pathways. Eur J Pharmacol 650(1):120–129PubMedCrossRef
20.
Koek GH, Liedorp PR, Bast A (2011) The role of oxidative stress in non-alcoholic steatohepatitis. Clin Chim Acta 412(15–16):1297–1305PubMedCrossRef
21.
Lee JM, Calkins MJ, Chan K, Kan YW, Johnson JA (2003) Identification of the NF-E2-related factor-2-dependent genes conferring protection against oxidative stress in primary cortical astrocytes using oligonucleotide microarray analysis. J Biol Chem 278(14):12029–12038PubMedCrossRef
22.
Hayes JD, McMahon M (2009) NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci 34(4):176–188PubMedCrossRef
23.
Harvey CJ, Thimmulappa RK, Singh A et al (2009) Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med 46(4):443–453PubMedPubMedCentralCrossRef
24.
Khor TO, Huang MT, Kwon KH et al (2006) Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res 66(24):11580–11584PubMedCrossRef
25.
Cheung KL, Lee JH, Khor TO et al (2014) Nrf2 knockout enhances intestinal tumorigenesis in Apc (min/+) mice due to attenuation of anti-oxidative stress pathway while potentiates inflammation. Mol Carcinog 53:77–84PubMedCrossRef
26.
Sykiotis GP, Habeos IG, Samuelson AV, Bohmann D (2011) The role of the antioxidant and longevity-promoting Nrf2 pathway in metabolic regulation. Curr Opin Clin Nutr Metab Care 14(1):41–48PubMedPubMedCentralCrossRef
27.
Tanaka Y, Aleksunes LM, Yeager RL et al (2008) NF-E2-related factor 2 inhibits lipid accumulation and oxidative stress in mice fed a high-fat diet. J Pharmacol Exp Ther 325(2):655–664PubMedCrossRef
28.
Yates MS, Tran QT, Dolan PM et al (2009) Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct gene expression profiles between Keap1 knockout and triterpenoid-treated mice. Carcinogenesis 30(6):1024–1031PubMedPubMedCentralCrossRef
29.
Jeong WS, Kim IW, Hu R, Kong AN (2004) Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway. Pharm Res 21(4):661–670PubMedCrossRef
30.
Cheng AS, Cheng YH, Chiou CH, Chang TL (2012) Resveratrol upregulates Nrf2 expression to attenuate methylglyoxal-induced insulin resistance in Hep G2 cells. J Agric Food Chem 60(36):9180–9187PubMedCrossRef
31.
Yu Z, Shao W, Chiang Y et al (2011) Oltipraz upregulates the nuclear factor (erythroid-derived 2)-like 2 [corrected](NRF2) antioxidant system and prevents insulin resistance and obesity induced by a high-fat diet in C57BL/6J mice. Diabetologia 54(4):922–934PubMedCrossRef
32.
Zhang YK, Yeager RL, Tanaka Y, Klaassen CD (2010) Enhanced expression of Nrf2 in mice attenuates the fatty liver produced by a methionine- and choline-deficient diet. Toxicol Appl Pharmacol 245(3):326–334PubMedPubMedCentralCrossRef
33.
Chowdhry S, Nazmy MH, Meakin PJ et al (2010) Loss of Nrf2 markedly exacerbates nonalcoholic steatohepatitis. Free Radic Biol Med 48(2):357–371PubMedCrossRef
34.
Khor TO, Huang Y, Wu TY et al (2011) Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem Pharmacol 82(9):1073–1078PubMedCrossRef
35.
Ramirez-Tortosa MC, Ramirez-Tortosa CL, Mesa MD et al (2009) Curcumin ameliorates rabbits’s steatohepatitis via respiratory chain, oxidative stress, and TNF-alpha. Free Radic Biol Med 47(7):924–931PubMedCrossRef
36.
Rao DS, Sekhara NC, Satyanarayana MN, Srinivasan M (1970) Effect of curcumin on serum and liver cholesterol levels in the rat. J Nutr 100(11):1307–1315PubMed
37.
Hu GX, Lin H, Lian QQ et al (2013) Curcumin as a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase 1: improving lipid profiles in high-fat-diet-treated rats. PLoS ONE 8(3):e49976PubMedPubMedCentralCrossRef
38.
Shin SK, Ha TY, McGregor RA, Choi MS (2011) Long-term curcumin administration protects against atherosclerosis via hepatic regulation of lipoprotein cholesterol metabolism. Mol Nutr Food Res 55(12):1829–1840PubMedCrossRef
39.
Asai A, Miyazawa T (2001) Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. J Nutr 131(11):2932–2935PubMed
Metadata
Title
Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation-mediated effect?
Authors
B. Li
L. Wang
Q. Lu
W. Da
Publication date
01-02-2016
Publisher
Springer London
Published in
Irish Journal of Medical Science (1971 -) / Issue 1/2016
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-014-1226-9

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