- Volume 16 Issue 1
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Hepatoprotective Effects of Curcumin Against Diethyl Nitrosamine Induced Hepatotoxicity in Albino Rats
- Kadasa, Naif Mohammed (Department of Biological Sciences, Faculty of Science, King Abdulaziz University) ;
- Abdallah, Haytham (Department of Biochemistry, Faculty of Veterinary Medicine, Zagazig University) ;
- Afifi, Mohamed (Department of Biological Sciences, Faculty of Science, King Abdulaziz University) ;
- Gowayed, Salah (Department of Biological Sciences, Faculty of Science, King Abdulaziz University)
- Published : 2015.02.04
Curcumin is widely used as a traditional medicine. This work was aimed to investigate its possible protective effect against chemically induced hepatocellular carcinoma (HCC) in rats. Fifty male albino rats were divided into five groups (n=10, each). The control group received a single dose of normal saline, the diethylnitrosamine (DENA) group received a single intra-peritoneal dose at 200mg/kg body weight, and the 3rd, 4th and 5th groups were given DENA and daily administrated curcunine (CUR) via intra-gastric intubation in doses of 300, 200 and 100 mg/kg b.wt. respectively for 20 weeks. Serum, and liver samples were used for determination of alpha feto-protein (AFP), interleukin-2 (IL-2), interleukine-6 (IL-6), serum liver enzymes (AST, ALT, ALP and GGT) levels as well the activities and gene expression of glutathione peroxidise (GPx), glutathione reductase (GR), catalase (CAT) and super oxide dismutase (SOD). Curcumin significantly lowered the serum levels of AFP, IL-2 and IL-6, ALT, ALT, and malondialdehyde (MDA) as well gene expression of IL-2 and IL-6. In contrast it increased the gene expression and activities of Gpx, GRD, CAT and SOD. The protective effect of CUR against DEN-induced hepatocarcinogenesis in albino rats was proven.
Supported by : King Abdulaziz University
- Ahmed O, Mohamed B, Mahmoud A (2014). Curcumin and naringin prevent 7,12- dimethylbenz(a)anthracene-induced hepatic injury by suppressing inflammation and oxidative stress. J Internat Academic Res Multidisciplinary, 2, 589-606.
- Ali A, Afifi M, Abdelazim A, Mosleh Y (2014) Quercetin and omega 3 ameliorate oxidative stress induced by aluminium chloride in the Brain. J Mol Neurosci, 53, 654-660 https://doi.org/10.1007/s12031-014-0232-8
- Al-Rejaie SS, Aleisa AM, Al-Yahya AA, et al (2009). Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats. World J Gastroenterol, 15, 1373-80 https://doi.org/10.3748/wjg.15.1373
- Bancroft J, Gamble M (2008). (Theory and Practice of Histological Technique) 4th Ed., Churchill, Livingston, New York, London, San Francisco, Tokyo.
- Bendong C, Mingliang N, Guangshun Y (2012). Effect of paeonol on antioxidant and immune regulatory activity in HCC Rats. Molecules, 17, 4672-83. https://doi.org/10.3390/molecules17044672
- Chen Y, Chen C, Chen J, Tsauer W, Hsu S (2003). Non cantharidin-induced apoptosis is via the extracellular signalregulated kinase and c-Jun-NH2-terminal kinase signaling pathway in human hepatoma Hep G2 cells. Br J Pharmacol, 140, 461-70. https://doi.org/10.1038/sj.bjp.0705461
- Chuang S, Kuo M, Hsu C, et al (2000). Curcumin-containing diet inhibits diethyl-nitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis, 21, 331-5. https://doi.org/10.1093/carcin/21.2.331
- Ciftci O, Aydin M, Ozdemir I, Vardi N (2012). Quercetin prevents 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-induced testicular damage in Rats. Andrologia, 44 ,164-173. https://doi.org/10.1111/j.1439-0272.2010.01126.x
- Corson T, Crews C (2007). Molecular understanding and modern application of traditional medicines. Triumphs and trials. Cell, 130, 769-74. https://doi.org/10.1016/j.cell.2007.08.021
- Fujioka S, Sclabas G, Schmidt C, et al (2003). Function of nuclear factor kappa B in pancreatic cancer metastasis. Clin Cancer Res, 9, 346-354.
- Ganesh C ,Bharat B (2007). Spicing Up of the Immune System by Curcumin. J Clin Immunol, 27,19-43. https://doi.org/10.1007/s10875-006-9066-7
- Gopal P, Paul M, Pau S (2014). Curcumin induces caspase mediated apoptosis in JURKAT cells by disrupting the redox balance. Asian Pac J Cancer Prev, 15, 93-100. https://doi.org/10.7314/APJCP.2014.15.1.93
- Ismail M, Iqbal Z, Khattak M, Javaid A, Khan T (2011). Prevalence, types and predictors of potential drug-drug interactions in pulmonology ward of a tertiary care hospital. Afr J Pharm Pharmacol, 5, 1303-9. https://doi.org/10.5897/AJPP11.408
- Katriina H, Shah E, Debbie A (2008). Systematic review of the association between circulating interleukin-6 (IL-6) and cancer. European J Cancer, 44, 937-45. https://doi.org/10.1016/j.ejca.2008.02.047
- Kaushik S, Kaur J (2003). Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clin Chim Acta, 333, 69-77. https://doi.org/10.1016/S0009-8981(03)00171-2
- Lane D, Matte I, Rancourt C (2011). Prognostic significance of IL-6 and IL-8 ascites levels in ovarian cancer patients. BMC Cancer, 11, 210. https://doi.org/10.1186/1471-2407-11-210
- Liovet J, Di Bisceglie A, Bruix J, et al (2008). Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst, 100, 698-711. https://doi.org/10.1093/jnci/djn134
- Lo C, Chen M, Hsiao M (2011). IL-6 trans-signaling information and progression of malignant ascites in ovarian cancer. Cancer Res, 71, 424-34.
- Mallikarjun P, Keyur A, Sheth C, Adarsh A (2013). Elevated Alpha Fetoprotein, No Hepatocellular Carcinoma. JCEH, 3, 162-4.
- Mantovani G, Maccio A, Madeddu C (2003). Antioxidant agents are effective in inducing lymphocyte progression through cell cycle in advanced cancer patients: assessment of the most important laboratory indexes of cachexia and oxidative stress. J Mol Med, 81, 664-73. https://doi.org/10.1007/s00109-003-0476-1
- Mohamed A, Metwally N, Mohamed S, Hassan E (2010). Protective capacity of butanolic extract of myoporum laetum against oxidative stress and immune disorder induced tissue damage in profenofos intoxicated rats. Int J Acad Res, 2, 157-164.
- Olivier F, Peter J, Margaret J (1995). Spontaneous acceptance of rat liver allografts is associated with an early down regulation of intra graft interleukin-4 messenger RNA expression. Hepatol, 21, 767-75.
- Oscar A, Bernardo C, Daniela M, et al (2007). The progressive elevation of alpha fetoprotein for the diagnosis of hepatocellular carcinoma in patients with liver cirrhosis. BMC Cancer, 7, 28. https://doi.org/10.1186/1471-2407-7-28
- Parker J, Roe S, Barford D (2004). Crystal structure of a PIWI protein suggests mechanisms for siRNA recognition and slicer activity. EMBO J, 23, 4727-37. https://doi.org/10.1038/sj.emboj.7600488
- Preetha A, Ajaikumar B, Robert A, Bharat B (2007). Bioavailability of curcumin: problems and promises. Mol Pharm, 4, 807-18. https://doi.org/10.1021/mp700113r
- Preetha A, Chitra S, Sonia J, et al (2008). Curcumin and cancer: an "old-age" disease with an "age-old" solution," Cancer Let, 267, 133-164. https://doi.org/10.1016/j.canlet.2008.03.025
- Rabinovich A, Medina L and Piura B (2011). Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6. Anticancer Res, 27, 267-72.
- Soresi M, Magliarisi C, Campagna P, et al (2003). Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma. Anticancer Res, 23, 1747-53.
- Sreepriya M, Bali G (2006). Effects of administration of embelin and curcumin on lipid peroxidation, hepatic glutathione antioxidant defense and hematopoietic system during N-nitrosodiethylamine/ phenobarbital-induced hepatocarcinogenesis in Wistar rats. Mol Cell Biochem, 284, 49-55. https://doi.org/10.1007/s11010-005-9012-7
- Subudhi U, Chainy G (2010). Expression of hepatic antioxidant genes in L-thyroxine-induced hyperthyroid rats: Regulation by vitamin E and Curcumin. Chem Biol Interact, 183, 304-16. https://doi.org/10.1016/j.cbi.2009.11.004
- Vietri M, Pietrabissa A, Mosca F, et al (2003). Curcumin is a potent inhibitor of phenol sulfo-transferase (SUIT1A1) in human liver and extra-hepatic tissue. Xenobiotica, 33, 357-63. https://doi.org/10.1080/0049825031000065197
- Wen-jun M, Hai-yong W, Li-song T (2013). Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol, 11, 212-9. https://doi.org/10.1186/1477-7819-11-212
- Yao DF, Dong ZZ, Yao DB, et al (2004). Abnormal expression of hepatoma-derived gamma-glutamyltransferase subtyping and its early alteration forcarcinogenesis of hepatocytes. Hepatobiliary Pancreat Dis Int, 3, 564-70.
- Youns M, Abdel Wahab A, Hassan Z, Attia M (2013). Serum talin-1 is a potential novel biomarker for diagnosis of hepatocellular carcinoma in Egyptian patients. Asian Pac J Cancer Prev, 14, 3819-23 https://doi.org/10.7314/APJCP.2013.14.6.3819
- Zekri Ael-R, Nassar AA, El-Din El-Rouby MN, et al (2013). Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is associated with increasing DNA promoter methylation. Asian Pac J Cancer Prev, 14, 6721-6. https://doi.org/10.7314/APJCP.2013.14.11.6721
- Zhang J, Wang R, Ma YY, et al (2013). Association between single nucleotide polymorphisms in miRNA196a-2 and miRNA146a and susceptibility to hepatocellular carcinoma in a Chinese population. Asian Pac J Cancer Prev, 14, 6427-31. https://doi.org/10.7314/APJCP.2013.14.11.6427
- Zhao J, Peng L, Geng C, et al (2014). Preventive effect of hydrazinocurcumin on carcinogenesis of diethylnitrosamineinduced hepatocarcinoma in male SD Rats. Asian Pac J Cancer Prev, 15, 2115-21 https://doi.org/10.7314/APJCP.2014.15.5.2115
- Zhaohui L, Tianxia L, Dejun Y, et al (2013). Curcumin protects against rotenone-induced neurotoxicity in cell and drosophila models of Parkinson's disease. Adv Parkinson's Dis, 2, 18-27. https://doi.org/10.4236/apd.2013.21004
- Zhong C, Li H, Liu D, et al ( 2014). Clinical study of hepatectomy combined with jianpi huayu therapy for hepatocellular carcinoma. Asian Pac J Cancer Prev, 15, 5951-7 https://doi.org/10.7314/APJCP.2014.15.14.5951
- Zhu WJ, Huang CY, Li C, et al (2013). Risk factors for early recurrence of HBV-related hepatocellular carcinoma meeting Milan criteria after curative resection. Asian Pac J Cancer Prev, 14, 7101-6. https://doi.org/10.7314/APJCP.2013.14.12.7101