PROTECTIVE EFFECTS OF ZINGIBER OFFICINALE AGAINST CARBON TETRACHLORIDE INDUCED LIVER FIBROSIS
Abstract
Objective: Liver plays a pivotal role in regulating various physiological processes in the body such as metabolism, secretion, and storage. It has a great capacity to detoxify toxic substances and synthesize useful principles. The current study was designed to investigate the possible protective effects of Zingiber officinale (ginger) extract on liver fibrosis induced by carbon tetrachloride (CCl4) in rats.
Methods: The animals were divided into four groups with eight rats in each. To induce liver fibrosis, Wistar albino rats received CCl4 (2 ml/kg diluted in corn oil) twice weekly for eight weeks. Rats were concurrently treated with Z. officinale extract at two different doses (300 and 600 mg/kg/day).
Results: CCl4 ÂÂinduced liver injury characterized by fibrotic changes, degenerated hepatocytes and focal accumulation of inflammatory cells. In addition, CCl4 administration produced a significant increase in serum aminotransferases, lipids, liver lipid peroxidation and nitric oxide. The hepatoprotective effects of Z. officinale extract were evidenced by the significant decrease in serum aminotransferases and liver lipid peroxidation. Further, concurrent treatment with either dose of Z. officinale enhanced liver glutathione and enzymatic antioxidant defenses.
Conclusion: Z. officinale showed a marked hepatoprotective effect against CCl4–induced liver fibrosis and injury through the abolishment of oxidative stress and potentiation of the antioxidant defense system.
Keywords: Antioxidant, Ginger, Fibrosis, Oxidative stress
Downloads
References
Arias IM. The liver: biology and pathobiology. Clin Nutr Insight 1988;14:5.
Tiwari Bk, Khosa Rl. Evaluation of the hepatoprotective and antioxidant effect of berberis asiatica against experimentally induced liver injury in rats. Int J Pharm Pharm Sci 2010;2:92-7.
Mitra SK, Venkataranganna MV, Sundaram R, Gopumadhavan S. Effect of HD-03, an herbal formulation, on the antioxidant defense system in rats. Phytother Res 1998;12:114-7.
Sala E, Guasch L, Iwaszkiewicz J, Mulero M, Salvadó MJ, Bladé C, et al. Identification of human IKK-2 inhibitors of natural origin (Part II): in silico prediction of IKK-2 inhibitors in natural extracts with known anti-inflammatory activity. Eur J Med Chem 2011;46:6098-103.
Sashidhara KV, Singh SP, Srivastava A, Puri A, Chhonker YS, Bhatta RS, et al. Discovery of a new class of HMG-CoA reductase inhibitor from Polyalthia longifolia as potential lipid-lowering agent. Eur J Med Chem 2011;46:5206-11.
Khushtar M, Kumar V, Javed K, Bhandari U. Protective effect of ginger oil on aspirin and pylorus ligation induced gastric ulcer model in rats. Int J Pharm Pharm Sci 2009;71:554-8.
Jeena K, B Liju V, Kuttana R. Antitumor and cytotoxic activity of ginger essential oil (Zingiber Officinale Roscoe). Int J Pharm Pharm Sci 2015;7;341-4.
Weidner MS, Sigwart K. Investigation of the teratogenic potential of a Zingiber officinale extract in the rat. Reprod Toxicol 2001;15:75–80.
Lantz RC, Chen GJ, Sarihan M, Sَlyom AM, Jolad SD, Timmermann BN. The effect of extracts from ginger rhizome on inflammatory mediator production. Phytomedicine 2007;14:123–8.
Aeschbach R, Loliger J, Scott BC, Murcia A, Butler J, Halliwell B, et al. Antioxidant actions of thymol, carbacrol, 6-gingerol, zingerone and hydroxytyrosol. Food Chem Toxicol 1994;2:31–6.
Sepahvand R, Esmaeili-Mahani S, Arzi A, Rasoulian B, Abbasnejad M. Ginger (Zingiber officinale Roscoe) elicits antinociceptive properties and potentiates morphine-induced analgesia in the rat radiant heat tail-flick test. J Med Food 2010;13:1397-401.
Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56-63.
Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of serum total cholesterol. Clin Chem 1974;20:470-5.
Fossati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 1982;28:2077-80.
Burstein M, Scholnick HR, Morfin R. Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 1970;11;583-95.
Tietz NW. Clinical guide to laboratory tests. Philadelphia: W. B. Saunders Co; 1995.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.
Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62–71.
Berton TR, Conti CJ, Mitchell DL, Aldaz CM, Lubet, RA, Fischer SM. The effect of vitamin E acetate on ultraviolet-induced mouse skin carcinogenesis. Mol. Carcinogen 1998;23:175–84.
McCord JM. Mutant mice, Cu, Zn superoxide dismutase, and motor neuron degeneration. Science 1994;266:1586–87.
Wendel A. Glutathione peroxidase. Methods Enzymol 1981;77:325–33.
Coskun O, Yakan B, Oztas E, Sezen A. Antioxidant and hepatoprotective activity of vitamin E and EGb 761 in experimental endotoxemic rats. Turk J Med Sci 2000;30:27–9.
Pezzuto JM. Plant-derived anticancer agents. Biochem Pharmacol 1997;l53:121-33.
Park EJ, Pezzuto JM. Botanicals in cancer chemoprevention. Cancer Metastasis Rev 2002;21:231-55.
Kikusaki H, Nakatani N. Antioxidant effect of some ginger constituents. J Food Sci 1993;58:1407-10.
Sekiwa Y, Kubota K, Kobayashi A. Isolation of novel glucosides related to gingerdiol from ginger and their antioxidative activities. Agric Food Chem 2000;48:373.
Rajesh MG. Latha MS. Protective activity of Glycyrrhiza glabra Linn. on carbon tetrachloride-induced peroxidative damage. Indian J Pharmacol 2004;36:284-7.
Motawi TK, Hamed MA, Shabana MH, Hashem RM, AboulNaser AF. Zingiber officinale acts as a nutraceutical agent against liver fibrosis. Nutr Metab 2011;8:40.
Han LK, Gong XJ, Kawano S, Saito M, Kimura Y, Okuda H. Antiobesity actions of Zingiber officinale Roscoe. Yakugaku Zasshi 2005;125:213-7.
Ramakrishna RR, Platel K, Srinivasan K. In vitro influence of spices and spice-active principles on digestive enzymes of rat pancreas and small intestine. Nahrung 2003;47:408-2.
Liu N, Huo G, Zhang L, Zhang X. Abstract (Effect of Zingiber Officinale Rosc on lipid peroxidation in hyperlipidemia rats). Weisheng Yanjiu 2003;32:22-3.
Hashimoto K, Satoh K, Murata P, Makino B, Sakakibara I, Kase Y, et al. Component of Zingiber officinale that improves the enhancement of small intestinal transport. Planta Med 2002;68:936-69.
Srinivasan K, Sambaiah K. The effect of spices on cholesterol 7 alpha-hydroxylase activity and on serum and hepatic cholesterol levels in the rat. Int J Vitam Nutr Res 1991;61:364-9.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.
Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L and Urticadioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 2005;11:6684-8.
Nevin KG, Vijayamma L. Effect of aervalanata against hepatotoxicity of carbon tetrachloride in rats. Environ Toxicol Pharmacol 2005;20:471-7.
Barcelos GR, Grotto D, Serpeloni JM, Aissa AF, Antunes LM, Knasmüller S, et al. Bixin and norbixin protect against DNA-damage and alterations of redox status induced by methylmercury exposure in vivo. Environ Mol Mutagen 2012;53:535–41.
Ross D, Moldeus P. Antioxidant defense systems and oxidative stress. In Membrane lipid oxidation. Boca Raton CRC Press: Vigo-Pelfrey C; 1991. p. 151–70.
Ansari MN, Bhandari U, Pillai KK. Ethanolic Zingiber officinale R Extract pretreatment alleviates isoproterenol-induced oxidative myocardial necrosis in rats. Indian J Exp Biol 2006;44:892–7.
Jung HW, Yoon CH, Park KM, Han HS, Park YK. Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. Food Chem Toxicol 2009;47:1190–7.
Li F, Wang Y, Parkin KL, Nitteranon V, Liang J, Yang W, et al. Isolation of quinone reductase (QR) inducing agents from ginger rhizome and there in vitro anti-inflammatory activity. Food Res Int 2011;44:1597-603.
Ippoushi K, Azuma K, Ito H, Horie H, Higashio H. [6]-Gingerol inhibits nitric oxide synthesis in activated J774.1 mouse macrophages and prevents peroxynitrite-induced oxidation and nitration reactions. Life Sci 2003;73:3427-37.
Ippoushi K, Takeuchi A, Ito H, Horie H, Azuma K. Antioxidative effects of daikon sprout (Raphanus sativus L.) and ginger (Zingiber officinale Roscoe) in rats. Food Chem 2007;102:237-42.
Dugasani S, Pichika MR, Nadarajah VD, Balijepalli MK, Tandra S, Korlakunta JN. Comparative antioxidant and anti-inflammatory effects of [6]-gingerol, [8]-gingerol, [10]-gingerol and [6]-shogaol. J Ethnopharmacol 2010;127:515-20.
Pascussi JM, Maure P, Vilarem M. Response to Zhou et al. J Clin Invest 2006;116:2564.