Abstract
Aflatoxin B1 is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Lipid peroxidation and oxidative DNA damage are the principal manifestations of aflatoxin B1-induced toxicity that could be counteracted by antioxidants. Many plant constituents have been reported to prevent liver damage associated with lipid peroxidation. In this study, curcumin (polyphenolic antioxidant purified from turmeric) and resveratrol (polyphenol obtained from grapes) were evaluated for possible protection against liver injury induced by aflatoxin B1 in rats. Adult male Fischer rats were divided into six groups including untreated control, curcumin control (200 mg/kg BW), resveratrol control (10 mg/kg BW) and aflatoxin B1 (25 μg/kg BW). Other two groups were administered either curcumin or resveratrol along with aflatoxin B1. The study was carried out for 90 days. At the end of the experiment period, blood and tissue samples were collected from the animals before they were killed. Livers were collected for histopathologic studies and fixed in 10% buffered formalin solution. Serum was used for estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (γ-GT) enzymes. The lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were estimated in liver homogenates. The results revealed that aflatoxin B1 administration caused liver damage as indicated by statistically significant (P < 0.05) increase in serum ALT, AST and γ-GT levels. In addition, there were general statistically significant reductions in the activities of GSH, SOD, CAT, GSH-Px, and an increase in lipid peroxidation in the liver of aflatoxin B1-treated group compared to the untreated control group. Curcumin showed a significant hepatoprotective activity by lowering the levels of serum marker enzymes, lipid peroxidation and elevating the levels of GSH, SOD, CAT and GSH-Px. However, resveratrol failed to protect from the aflatoxin B1-induced liver injury. These findings suggest that curcumin but not resveratrol has a hepatoprotective effect against aflatoxin B1-induced liver injury.
Similar content being viewed by others
Abbreviations
- AFB1 :
-
Aflatoxin B1
- BW:
-
Body weight
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- γ-GT:
-
γ-Glutamyl transferase
- GSH:
-
Reduced glutathione
- SOD:
-
Superoxide dismutase
- CAT:
-
Catalase
- GSH-Px:
-
Glutathione peroxidase
- TBARS:
-
Thiobarbituric acid reactive substances
- MDA:
-
Malondialdehyde
References
Ammon HP, Walh MA (1991) Pharmacology of Curcuma longa. Planta Med 57:1–7
Ara C, Kirimlioglu H, Karabulut AB, Coban S, Ay S, Harputluoglu M, Kirimlioglu V, Yilmaz S (2005) Protective effect of resveratrol against oxidative stress in cholestasis. J Surg Res 127:112–117
Bedard LL, Massey TE (2006) Aflatoxin B1-induced DNA damage and its repair. Cancer Lett 241:174–183
Chainani-Wu N (2003) Safety and anti-inflammatory activity of curcumin: a component of turmeric (curcumin longa). J Altern Comp Med 9:161–168
Chen CK, Pace-Asciak CR (1996) Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen Pharmacol 27:363–366
Choudhary A, Verma RJ (2005) Ameliorative effect of black tea extract on aflatoxin induced lipid peroxidation in the liver of mice. Food Chem Toxicol 43:99–104
Cleveland TE, Dowd PF, Desjardins AE, Bhatnagar D, Cotty PJ (2003) United States department of agriculture–agricultural research service, research on pre-harvest prevention of mycotoxins and mycotoxigenic fungi in US crops. Pest Manag Sci 59:629–642
Donatus IA, Sardjoko, Vermeulen NP (1990) Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes. Biochem Pharmacol 39:1869–1875
Duvoix A, Blasius R, Delhalle S, Schnekenburger M, Morceau F, Henry E, Dicato M, Diederich M (2005) Chemopreventive and therapeutic effects of curcumin. Cancer Lett 223:181–190
Frémont L, Belguendouz L, Delpal S (1999) Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 64:2511–2522
Günzler WA, Kremers H, Flohé L (1974) An improved coupled test procedure for glutathione peroxidase (EC 1–11-1–9-) in blood. Z Klin Chem Klin Biochem 12:444–448
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S (2003) Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol 92:33–38
Kang HC, Nan JX, Park PH, Kim JM, Lee SH, Woo SW, Zhao YZ, Park EJ, Sohn DH (2002) Curcumin inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. J Pharm Pharmacol 54:119–126
Kempaiah RK, Srinivasan K (2004) Influence of dietary curcumin, capsaicin and garlic on the antioxidant status of red blood cells and the liver in high-fat-fed rats. Ann Nutr Metab 48:314–320
Leonard SS, Xia C, Jiang BH, Stinefelt B, Klanforf H, Harris GK, Shi X (2003) Resveratrol scavenges reactive oxygen species and effects radical induced cellular responses. Biochem Biophys Res Commun 309:1017–1026
Lin JK, Tsai SH (1999) Chemoprevention of cancer and cardiovascular disease by resveratrol. Proc Natl Sci Counc Repub China B 23:99–106
López-Vélez M, Martínez-Martínez F, Del Valle-Ribes C (2003) The study of phenolic compounds as natural antioxidants in wine. Crit Rev food Sci Nut 43:233–244
McKillop IH, Moran DM, Jin X, Koniaris LG (2006) Molecular pathogenesis of hepatocellular carcinoma. J Surg Res 136:125–135
Meki MA, Esmail DF, Hussein AA, Hassanein HM (2004) Caspase-3 and heat shock protein-70 in rat liver treated with aflatoxin B1: effect of melatonin. Toxicon 43:93–100
Mgbonyebi OP, Russo J, Russo IH (1998) Antiproliferative effect of synthetic resveratrol on human breast epithelial cells. Int J Oncol 12:865–869
Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and simple assay for superoxide dismutase. J Biol Chem 247:3170–3175
Mitchell SH, Zhu W, Young CY (1999) Resveratrol inhibits the expression and function of the androgen receptor in LNCaP prostate cancer cells. Cancer Res 59:5892–5895
Naaz F, Javed S, Abdin MZ (2007) Hepatoprotective effect of ethanolic extract of Phyllanthus amarus Schum. et Thonn. on aflatoxin B1-induced liver damage in mice. J Ethnopharmacol 113:503–509
Ozen H, Karaman M, Ciğremiş Y, Tuzcu M, Ozcan K, Erdağ D (2009) Effectiveness of melatonin on aflatoxicosis in chicks. Res Vet Sci 86:485–489
Pace-Asciak CR, Hahn S, Diamandis EP, Soleas G, Goldberg DM (1995) The red wine phenolics trans-resveratrol and quercetin block human platelet aggregation and eicosanoid synthesis: implications for protection against coronary heart disease. Clin Chim Acta 235:207–219
Park EJ, Jeon CH, Ko G, Kim J, Sohn DH (2000) Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol 52:437–440
Persijn JP, van der Silk W (1976) A new method for the determination of gamma-glutamyltransferase in serum. J Clin Chem Clin Biochem 14:421–427
Preston RJ, Williams GM (2005) DNA-reactive carcinogens: mode of action and human cancer hazard. Crit Rev Toxicol 35:673–683
Recknagel RO, Glende EA, Dolak JA, Waller RL (1989) Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 43:139–154
Reitman S, Frankel S (1957) A colorimetric method for the determination of serum glutamic oxalacetic acid and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–63
Reyes-Gordillo K, Segovia J, Shibayama M, Vergara P, Moreno MG, Muriel P (2007) Curcumin protects against acute liver damage in the rat by inhibiting NF-kappaB, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta 1770:989–996
Rukkumani R, Aruna K, Varma PS, Rajasekaran KN, Menon VP (2004) Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress. J Pharm Pharm Sci 7:274–283
Schneider Y, Vincent F, Duranton B, Badolo L, Gosse F, Bergmann C, Seiler N, Raul F (2000) Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett 158:85–91
Sedlak J, Lindsay RH (1968) Estimation of total, proteinbound and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analyt Biochem 25:192–205
Shapiro H, Ashkenazi M, Weizman N, Shahmurov M, Aeed H, Bruck R (2006) Curcumin ameliorates acute thioacetamide-induced hepatotoxicity. J Gastroenterol Hepatol 21:358–366
Shen HM, Shi CY, Lee HP, Ong CN (1994) Aflatoxin B1-induced lipid peroxidation in rat liver. Toxicol Appl Pharmacol 127:145–150
Shukla Y, Aroro A, Taneja P (2002) Antimutagenic potential of curcumin on chromosomal aberrations in Wistar rats. Mutat Res 515:197–202
Sinha KA (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394
Smela ME, Currier SS, Bailey EA, Essigmann JM (2001) The chemistry and biology of aflatoxin B(1): from mutational spectrometry to carcinogenesis. Carcinogenesis 22:535
Soleas GJ, Diamandis EP, Goldberg DM (1997) Resveratrol: a molecule whose time has come? and gone? Clin Biochem 30:91–113
Srinivasan A, Menon VP (2003) Protection of pancreatic β-cell by the potential antioxidant bis-o-hydroxycinnamoyl methane, analogue of natural curcuminoid in experimental diabetes. J Pharm Pharm Sci 6:327–333
Su JL, Lin MT, Hong CC, Chang CC, Shiah SG, Wu CW, Chen ST, Chau YP, Kuo ML (2005) Resveratrol induces FasL-related apoptosis through Cdc42 activation of SK1/JNK-dependent signaling pathway in human leukemia HL-60 cells. Carcinogenesis 26:1–10
Sugiyama T, Nagata JC, Yamagishi A, Endoh K, Saito M, Yamada K, Yamada S, Umegaki K (2006) Selective protection of curcumin against carbon tetrachloride-induced inactivation of hepatic cytochrome P450 isozymes in rats. Life Sci 78:2188–2193
Towner RA, Qian SY, Kadiiska MB, Mason RP (2003) In vivo identification of aflatoxin-induced free radicals in rat bile. Free Radic Biol Med 35:1330–1340
Verma RJ, Mathuria N (2007) Curcumin ameliorates aflatoxin-induced lipid peroxidation in liver, kidney and testis of mice–an in vitro study. Acta Pol Pharm 64:413–416
Verma RJ, Mathuria N (2008) Curcumin ameliorates aflatoxin-induced lipid-peroxidation in liver and kidney of mice. Acta Pol Pharm 65:195–202
Vitaglione P, Ottanelli B, Milani S, Morisco F, Caporaso N, Fogliano V (2009) Dietary trans-resveratrol bioavailability and effect on CCl4-induced liver lipid peroxidation. J Gastroenterol Hepatol 24:618–622
Wei QY, Chen WF, Zhou B, Yang L, Liu ZL (2006) Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 1760:70–77
Wild CP, Hasewega R, Barraud L, Chutimataewin S, Chapot B, Ito N, Montesano R (1996) Aflatoxin albumin adducts: a basis for comparative carcinogenesis between animals and humans. Cancer Epidem Biom Prev 5:179–189
Yener Z, Celik I, Ilhan F, Bal R (2009) Effects of Urtica dioica L. seed on lipid peroxidation, antioxidants and liver pathology in aflatoxin-induced tissue injury in rats. Food Chem Toxicol 47:418–424
Zheng S, Yumei F, Chen A (2007) de novo synthesis of glutathione is a prerequisite for curcumin to inhibit HSC activation. Free Radic Biol Med 43:444–453
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
El-Agamy, D.S. Comparative effects of curcumin and resveratrol on aflatoxin B1-induced liver injury in rats. Arch Toxicol 84, 389–396 (2010). https://doi.org/10.1007/s00204-010-0511-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00204-010-0511-2