Influence of Pomegranate (Punica granatum L.) on Dimethoate Induced Hepatotoxicity in Rats
Pomegranate (Punica granatum L.) is an ancient fruit of great medical interest and rich source of antioxidants. Pesticides as dimethoate play a crucial role in the occurrence many diseases in plants, animal and human. Therefore the ability of Pomegranate (Punica granatum L.) to alleviate hepatotoxicity induced by organophosphate pesticide dimethoate was investigated. Albino male rats were divided randomly into 4 groups and kept at 7 animals per group in an environmentally controlled condition for 6 weeks. The first group was served as a control group (basal diet), the second group fed on basal diet supplemented with 5% freeze dried pomegranate seeds, the third group fed on 20 ppm dimethoate contaminated diet and the last group fed on dimethoate contaminated diet supplemented with 5% freeze dried pomegranate seeds. The results revealed that administration of dimethoate caused high significant increased in liver functions: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities as well as lipid peroxide (malonaldhyde, MDA); on the other hand high significant decreased on glutathione (GSH), glutathione peroxidase (GPx), albumin and total protein were observed. However addition of 5% freeze dried pomegranate seeds significantly improved all previously mentioned parameters. These results indicate the dimethoate induced hepatotoxicity and highlight the protective effect of pomegranate seeds as a potential protective agent against dimethoate induced hepatotoxicity. This may be attributed to the powerful antioxidants (polyphenols, total phenols, and total flavonoids) which present in high levels in pomegranate as well as improving the immunity by activation of antioxidant enzymes GSH and GPx.
[1] FAO, "Manual on the development and use of FAO specifications for plant protection products, 5th edition,” FAO plant production and protection paper, 149, FAO, Rome, 1999.
[2] M. Al-Haj, A. Nasser, and A. Anis, "Survey of pesticides used in qat cultivation in dhale and yafe and their adverse effects,” J. Nat. Appl. Sci., vol. 9, no.1, pp. 103-110, 2005.
[3] L. Nagymajtenyi, H. Schulz, A. Pappa, and I. Desi, "Developmental nrurotoxicological effects of lead and dimethoate in animal experiments,” Neurotoxicology, vol. 19, no. 4-5, pp. 617-622, 1998.
[4] H.H. Hagar, and A.H. Fahmy, "A biochemical, histochemical and ultrastructural evaluation of the effect of dimethoate intoxication on rat pancreas,” Toxicology Letters, vol.133, pp. 161-170, 2002.
[5] N.M. Aly, and K.S. El-Gend, "Effect of dimethoate on the immune system of female mice,” J. Environ. Sci. Health, vol. 35, no. 1, pp. 77-86, 2000.
[6] N.C. Rawlings, S.J. Cook, and D. Waldbilling, "Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, lindan, triallate, trifluralin, 2, 4-D and pentachlorophenol on the metabolic and reproductive endocrine system in Ewes,” J. Toxicol. Environ. Health, vol.54, pp. 21-36, 1998.
[7] J. Gomes, A.H. Dawodu, O. Lloyd, D.M. Revitt, and S.V. Anilal, "Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides,” Hum. Exp. Toxicol., vol.18, pp.33-37, 1999.
[8] F. Sayim, "Dimethoate-induced biochemical and histopathological changes in the liver of rat,” Experimental and Toxicologic Pathology, vol. 59, pp. 237-243, 2007.
[9] F.A, Khogali, J.B. Sheikh, S. Abdel Rahman, A. A. Rahim, and M.H. Daghestani, "Histopathological and Hematological Effects of Dimethoate 40EC on Some Organs of Albino Mice,” J. King Saud Univ., vol. 18, no.2, pp.73-87, 2005.
[10] P. Berny, "Pesticides and the intoxication of wild animals,” J. of Veterinary Pharmacology and Therapeutics, vol.30, no.2, pp. 93-100, 2007.
[11] E.M.A Salih, "Toxic effect of dimethoate and diazinon on the biochemical and hematological parameters in male rabbits,” Jordan J. of Biological Sciences, vol. 3, no.2, pp. 77-82, 2010.
[12] Y. Sharma Bashir, S. Irshad, M. Datta Gupta, and T.D. Dogra, "Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats,” Toxicology, vol. 206, pp. 49-57, 2005a.
[13] Y. Sharma Bashir, S. Irshad, M. Nag, and T.D. Dogra, "Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure, "Toxicology, vol. 215, pp. 173-181, 2005b.
[14] V. Sivapiriya Jayanthisakthisekaran, and S. Venkatraman, "Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phophorodithioate) and Ethanol in antioxidant status of liver and kidney of experimental mice,” Pesticide Biochem. Physiol., vol. 85, pp. 115-121, 2006.
[15] V. Kamath, A. K. R. Joshi, and P. S. Rajini, "Dimethoate induced biochemical perturbation in rat pancreas and its attenuation by cashew nut skin extract,” J. Nutr. Biochem., vol. 90, pp. 58-65, 2008.
[16] M. Akhgari, M. Abdollahi, A. Kebryaeezadeh, R. Hosseini, and O. Sabzevari, "Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for sub chronic toxicity of malathion in blood and liver of rats,” Hum. Exp. Toxicol., vol. 22, pp. 205-211, 2003.
[17] M. Abdollahi, A. Ranjbar, S. Shandnia, S. Nikfar, and A. Rezaiee, "Pesticides and oxidative stress: a review,” Med. Sci. Monit., vol. 10, pp. RA141-RA147, 2004.
[18] S. John, M. Kale, N. Rathone, and D. Bhatnagar, "Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes,” J. Nutr. Biochem., vol. 12, pp. 500-504, 2001.
[19] R.A. Jacob, and B. J. Burri, "Oxidative damage and defense,” Am. J. Clin. Nutr., vol. 63, pp. 985S-990S, 1996.
[20] J. A. Ross, and C.M. Kasum, "Dietary flavonoids: Bioavailability, metabolic effects, and safety,” Annu Rev Nutr; vol.22, pp.19–34, 2002.
[21] M.A. Soobrattee, T. Bahorun, and O.I. Aruoma, "Chemopreventive actions of polyphenolic compounds in cancer,” Biofactors, vol. 27, pp.19–35, 2006.
[22] S.D. Johanningsmeier, and G. K. Harris, "Pomegranate as a functional food and nutraceutical source,” Annu Rev Food Technol, vol. 2, pp. 181-201, 2011.
[23] L.F. Amorim, M.T. Catanho, D.A. Terra, K.C. Brandão, C.M .Holanda, L.H. Jales-Júnior, L.M. Brito, M.L. Gomes, V.G. De Melo, and M. Bernardo-Filho,” Cavalcanti Jales RL. Cell Mol Biol. (Noisy-le-grand),” Jun; vol.49, no.4, 501-507, 2003.
[24] E.P. Lansky, and RA. Newman, "Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer,” J. Ethnopharmacol., vol.109, pp.177–206, 2007.
[25] J.J. Hora,, E.R. Maydew, E.P. Lansky, and C. Dwivedi, "Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice,” J. Med. Food, vol.6, no. 3, pp. 157–161, 2003.
[26] N.D. Kim, R. Mehta, W. Yu, I. Neeman, T. Livney, A. Amichay, D. Poirier, P. Nicholls, A. Kirby, W. Jiang, R. Mansel, C. Ramachandran, T. Rabi, B. Kaplan, and E. Lansky, "Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer,” Breast Cancer Res. Treat., vol.71, pp.203–217, 2002.
[27] N. Khan, F. Afaq, M.H. Kweon, K. Kim, and H. Mukhtar, "Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice,” Cancer Res., vol. 67, pp. 3475–3482, 2007.
[28] H. Kohno, R. Suzuki, Y. Yasui, M. Hosokawa, and K. Miyashita, "Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats,” Cancer Sci., vol. 95, pp.481–486, 2004.
[29] I. Celik,, A. Temur, and I. Isik, "Hepatoprotective role and antioxidant capacity of pomegranate (Punica granatum) flowers infusion against trichloroacetic acid-exposed in rats,” Food Chem. Toxicol., vol.47, no.1, pp.145–149, 2009.
[30] A. Bishayee, B. Deepa, J. Roslin Thoppil, S. Altaf Darvesh, N. Eviatar, and P. Ephraim Lansky, "Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms,” Carcinogenesis, vol.32, no.6, pp.888–896, 2011.
[31] FAO-FAOSTAT, "Statistical database. Food and Agriculture Organization of the United Nations, Codex Alimentarius Commision: Tunis, Tunesia,” http:// www.fao.org, Accessed May 23, 2010.
[32] M. Gil, , F.A. Tornas, B. Hess-Pierce, D. Holcroft, and A.A. Manx Kader, "Antioxidant activity of pomegranate juice and its relationship with phenolic Composition and processing,” J .Agric. Food chem., vol. 48, pp.4581-4589, 2000.
[33] A.O.A.C, "Official Methods of the Association of Official Analytical Chemists, 17th ed. Published by the Association of Official Analytical Chemists,” Arlington Virginia, U.S.A, 2000.
[34] M. L. Pric, S. Van, L.G. Butler, "A critical evaluation of the vanillin reaction as an assay for tannin in sorghum grain,” J Agric Food Chem., vol. 26, pp.1214-1218, 1978.
[35] V.L. Singleton, R. Orthofer, and R.M. Lamuela- Raventos, "Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent, In: Packer, L (ed.), Oxidants and antioxidants, part A, " Methods Enzymology, vol. 299, Academic Press, New York, pp.152-178, 1999.
[36] S. Reitman, and S. Frankel, "Colorimetric method for aspartate and alanine transferase,” Am. J. Clin. Pathol., vol. 28, pp.56-63,1957.
[37] A.V. Roy, "Rapid method for determing alkaline phospatase activity in serum with thymoiphthalinmonosphate,” J. Clin. Chem., vol.16, pp.431-436, 1970.
[38] .T. Doumas, W.A. Watson, and H.G. Biggs, "Albumin standards and measurements of serum albumin with bromcresol green,” Clin. Chim. Acta., vol. 31, pp. 87-92, 1971.
[39] A.G. Gornall, C.J. Bardawill, and M.M. David, "Determination of serum proteins by means of the Biuret reaction,” J. Biol. Chem., vol.177, pp. 75-79, 1949.
[40] K. Satoh, "Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method Cline,” Chime. Act. Vol.90, pp.37-43, 1978.
[41] D.E. Paglia, and W.N. Valentine, "Studies on the quantitative and qualitative characterization of erythrocyte gluthione peroxidase,” J. Lab. Clin. Med., vol.70, pp.158-169, 1967.
[42] SAS/STAS, "User's Guide, Statistical analysis system institute, Cary, NC,” 1990.
[43] R. S. Ahmed, V. Seth, S. T. Pasha, and B. D. Banerjee, "Influence of dietary ginger (Zingiber officinals Rosc) on oxidative stress induced by malathion in rats,” Food Chem. Toxicol., vol. 38, no. 200, pp. 443-450, 2000.
[44] A. Zohair, "Protective effect of molokhia (Corchorus olitorius, L.) on malathion-induced hepatotoxicity in rats,” J. Agric s. Sci. Univ., vol.31, pp. 6111-6121, 2006.
[45] C.C. Hsu, C.C. Lin, T.S. Liao, and M. C. Yin, "Protective effect of -allyl cysteine and s-propyl cycteine on acetaminophen-induced hepatotoxicity in mice,” Food and Chemical Toxicology, vol.44, pp.393-397, 2006.
[46] M. Attia Ahmed, and M. Hoda Nasr, "Dimethoate-induced changes in biochemical parameters of experimental rat serum and its neutralization by black seed (Nigella Sativa) oil,” Slovak J. Anim. Sci., vol.42, no.2, pp.87–94, 2009.
[47] M. A. El-Damaty El-Sayed, H. Abdel-Razik Farrag, G. Rowayshed, and M. Hany Fahmy, "Biochemical and Histopathological Effects of Systemic Pesticides on Some Functional Organs of Male Albino Rats,” J. of Applied Sciences Research, vol.8, no.11, pp.5459-5469, 2012.
[48] I.S. Ashoush, O.I. El-Batawy, and G.A. El-Shourbagy, "Antioxidant activity and hepatoprotective effect of pomegranate peel and whey powders in rats,” Annals of Agricultural Science, vol. 5, vol. 4, pp. 334–343, 2013.
[49] Takeo, "Affinity electrophoresis” In: Advanced electrophoresis, Edit. Chrambach, A; Dunn, MJ and Radola, BJ, vol.1 VCH Publisher, Germany,” 1987.
[50] S. G. Yeragi, A. M .Rana, and V. A. Koli, "Effect of pesticides on protein metabolism of mudskipper Boleophthalmus Dussumieri,” J. Ecotoxicol. Environ. Monit. vol. 13, no. 2, pp. 211-214, 2003.
[51] M. Bhadauria, S. K .Nirala, and S. Shukla, "Hepato-protective efficacy of propolis extract: A biochemical and histopathological approach Iranian,” J. of Pharmacology & Therapeutics, vol.6, pp.145-154, 2007.
[52] H.S. Parmar, and A. Kar, "Protective role of Citrus sinensis, Musa paradisiacal, and punica granatum peels against diet–induced atherosclerosis and thyroid dysfunctions in rats,” Nutrition Research, vol. 27, pp.710-718, 2007.
[53] G. Wu, S. Fang Yun-Zhong, J.R. Yang Lupton, and N.D. Turner, "Glutathione metabolism and its implication for health, The American Society for Nutritional Sciences,” J. Nutr., vol.134, pp. 480-492, 2004.
[54] D. Jasprica, A. Mornar, , Z. Debeljak, A. Smoteie-Bubato, M. Medfc-Saric, L. Mayer, Z. Romic, K. Bucan, T. Balog, S. Sobocanec, and V. Sverko, "In vivo study of propolis supplementation effects on antioxidative status and red blood cells,” J. Ethnopharmacol, vol. 110, pp.548-554, 2007.
[55] O. Althunibat, A. Al-Mustafa, K. Tarawneh, K. Khleifat, B. Ridzwan, and H. Qaralleh, "Protective role of Punica granatum L. peel extract against oxidative damage in experimental diabetic rats,” Process Biochemistry, vol.45, pp.581–585, 2010.
[56] M.L. Urso, and P.M. Clarkson, "Oxidative stress, exercise and antioxidant supplementation,” Toxicology, vol.189, pp. 41-54, 2003.
[57] M. Laguerre, J. Lecomte, and P. Villeneuve, "Evaluation of the ability of antioxidants to counteract lipid oxidation: existing methods, new trends and challenges,” Progress in Lipid Research, vol.46, pp.244-282, 2007.
[58] M. Aviram, "Polyphenols from pomegranate juice, red wine, and licorice root protect against lipids peroxidation and attenuate cardiovascular diseases, in: S. Martens, D. Treutter, G. Forkmann (Eds.)"polyphenols 2000,"Proc.XXInt.Conf.polyphenols, 2002.
[59] S.U. Mertens-Talcott, P. Jilma-Stohlawetz, J. Rios, L. Hingorani, and H. Derendorf, "Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum L.) polyphenols after ingestion of a standardized extract in healthy volunteers,” J. Agric. Food Chem., vol.54, pp.8956–8961, 2006.
[60] M. Viuda-Martos, J. Fernández-López, and J.A. Pérez-Álvarez, "Pomegranate and Many Functional Components as Related to Human Health: A Review,” Comprehensive Reviews in Food Science and Food Safety, Vol.9, no.6, pp.635-654, ISSN 1541-4337, 2010.
[61] A. Al-Jarallah, F. Igdoura, A. Zhang, C. Tenedero, E. White, and M. MacDonald, "The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice,” Atherosclerosis xxx, 1e10, 2013.
[1] FAO, "Manual on the development and use of FAO specifications for plant protection products, 5th edition,” FAO plant production and protection paper, 149, FAO, Rome, 1999.
[2] M. Al-Haj, A. Nasser, and A. Anis, "Survey of pesticides used in qat cultivation in dhale and yafe and their adverse effects,” J. Nat. Appl. Sci., vol. 9, no.1, pp. 103-110, 2005.
[3] L. Nagymajtenyi, H. Schulz, A. Pappa, and I. Desi, "Developmental nrurotoxicological effects of lead and dimethoate in animal experiments,” Neurotoxicology, vol. 19, no. 4-5, pp. 617-622, 1998.
[4] H.H. Hagar, and A.H. Fahmy, "A biochemical, histochemical and ultrastructural evaluation of the effect of dimethoate intoxication on rat pancreas,” Toxicology Letters, vol.133, pp. 161-170, 2002.
[5] N.M. Aly, and K.S. El-Gend, "Effect of dimethoate on the immune system of female mice,” J. Environ. Sci. Health, vol. 35, no. 1, pp. 77-86, 2000.
[6] N.C. Rawlings, S.J. Cook, and D. Waldbilling, "Effects of the pesticides carbofuran, chlorpyrifos, dimethoate, lindan, triallate, trifluralin, 2, 4-D and pentachlorophenol on the metabolic and reproductive endocrine system in Ewes,” J. Toxicol. Environ. Health, vol.54, pp. 21-36, 1998.
[7] J. Gomes, A.H. Dawodu, O. Lloyd, D.M. Revitt, and S.V. Anilal, "Hepatic injury and disturbed amino acid metabolism in mice following prolonged exposure to organophosphorus pesticides,” Hum. Exp. Toxicol., vol.18, pp.33-37, 1999.
[8] F. Sayim, "Dimethoate-induced biochemical and histopathological changes in the liver of rat,” Experimental and Toxicologic Pathology, vol. 59, pp. 237-243, 2007.
[9] F.A, Khogali, J.B. Sheikh, S. Abdel Rahman, A. A. Rahim, and M.H. Daghestani, "Histopathological and Hematological Effects of Dimethoate 40EC on Some Organs of Albino Mice,” J. King Saud Univ., vol. 18, no.2, pp.73-87, 2005.
[10] P. Berny, "Pesticides and the intoxication of wild animals,” J. of Veterinary Pharmacology and Therapeutics, vol.30, no.2, pp. 93-100, 2007.
[11] E.M.A Salih, "Toxic effect of dimethoate and diazinon on the biochemical and hematological parameters in male rabbits,” Jordan J. of Biological Sciences, vol. 3, no.2, pp. 77-82, 2010.
[12] Y. Sharma Bashir, S. Irshad, M. Datta Gupta, and T.D. Dogra, "Effects of acute dimethoate administration on antioxidant status of liver and brain of experimental rats,” Toxicology, vol. 206, pp. 49-57, 2005a.
[13] Y. Sharma Bashir, S. Irshad, M. Nag, and T.D. Dogra, "Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure, "Toxicology, vol. 215, pp. 173-181, 2005b.
[14] V. Sivapiriya Jayanthisakthisekaran, and S. Venkatraman, "Effects of dimethoate (O,O-dimethyl S-methyl carbamoyl methyl phophorodithioate) and Ethanol in antioxidant status of liver and kidney of experimental mice,” Pesticide Biochem. Physiol., vol. 85, pp. 115-121, 2006.
[15] V. Kamath, A. K. R. Joshi, and P. S. Rajini, "Dimethoate induced biochemical perturbation in rat pancreas and its attenuation by cashew nut skin extract,” J. Nutr. Biochem., vol. 90, pp. 58-65, 2008.
[16] M. Akhgari, M. Abdollahi, A. Kebryaeezadeh, R. Hosseini, and O. Sabzevari, "Biochemical evidence for free radical-induced lipid peroxidation as a mechanism for sub chronic toxicity of malathion in blood and liver of rats,” Hum. Exp. Toxicol., vol. 22, pp. 205-211, 2003.
[17] M. Abdollahi, A. Ranjbar, S. Shandnia, S. Nikfar, and A. Rezaiee, "Pesticides and oxidative stress: a review,” Med. Sci. Monit., vol. 10, pp. RA141-RA147, 2004.
[18] S. John, M. Kale, N. Rathone, and D. Bhatnagar, "Protective effect of vitamin E in dimethoate and malathion induced oxidative stress in rat erythrocytes,” J. Nutr. Biochem., vol. 12, pp. 500-504, 2001.
[19] R.A. Jacob, and B. J. Burri, "Oxidative damage and defense,” Am. J. Clin. Nutr., vol. 63, pp. 985S-990S, 1996.
[20] J. A. Ross, and C.M. Kasum, "Dietary flavonoids: Bioavailability, metabolic effects, and safety,” Annu Rev Nutr; vol.22, pp.19–34, 2002.
[21] M.A. Soobrattee, T. Bahorun, and O.I. Aruoma, "Chemopreventive actions of polyphenolic compounds in cancer,” Biofactors, vol. 27, pp.19–35, 2006.
[22] S.D. Johanningsmeier, and G. K. Harris, "Pomegranate as a functional food and nutraceutical source,” Annu Rev Food Technol, vol. 2, pp. 181-201, 2011.
[23] L.F. Amorim, M.T. Catanho, D.A. Terra, K.C. Brandão, C.M .Holanda, L.H. Jales-Júnior, L.M. Brito, M.L. Gomes, V.G. De Melo, and M. Bernardo-Filho,” Cavalcanti Jales RL. Cell Mol Biol. (Noisy-le-grand),” Jun; vol.49, no.4, 501-507, 2003.
[24] E.P. Lansky, and RA. Newman, "Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer,” J. Ethnopharmacol., vol.109, pp.177–206, 2007.
[25] J.J. Hora,, E.R. Maydew, E.P. Lansky, and C. Dwivedi, "Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice,” J. Med. Food, vol.6, no. 3, pp. 157–161, 2003.
[26] N.D. Kim, R. Mehta, W. Yu, I. Neeman, T. Livney, A. Amichay, D. Poirier, P. Nicholls, A. Kirby, W. Jiang, R. Mansel, C. Ramachandran, T. Rabi, B. Kaplan, and E. Lansky, "Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer,” Breast Cancer Res. Treat., vol.71, pp.203–217, 2002.
[27] N. Khan, F. Afaq, M.H. Kweon, K. Kim, and H. Mukhtar, "Oral consumption of pomegranate fruit extract inhibits growth and progression of primary lung tumors in mice,” Cancer Res., vol. 67, pp. 3475–3482, 2007.
[28] H. Kohno, R. Suzuki, Y. Yasui, M. Hosokawa, and K. Miyashita, "Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats,” Cancer Sci., vol. 95, pp.481–486, 2004.
[29] I. Celik,, A. Temur, and I. Isik, "Hepatoprotective role and antioxidant capacity of pomegranate (Punica granatum) flowers infusion against trichloroacetic acid-exposed in rats,” Food Chem. Toxicol., vol.47, no.1, pp.145–149, 2009.
[30] A. Bishayee, B. Deepa, J. Roslin Thoppil, S. Altaf Darvesh, N. Eviatar, and P. Ephraim Lansky, "Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms,” Carcinogenesis, vol.32, no.6, pp.888–896, 2011.
[31] FAO-FAOSTAT, "Statistical database. Food and Agriculture Organization of the United Nations, Codex Alimentarius Commision: Tunis, Tunesia,” http:// www.fao.org, Accessed May 23, 2010.
[32] M. Gil, , F.A. Tornas, B. Hess-Pierce, D. Holcroft, and A.A. Manx Kader, "Antioxidant activity of pomegranate juice and its relationship with phenolic Composition and processing,” J .Agric. Food chem., vol. 48, pp.4581-4589, 2000.
[33] A.O.A.C, "Official Methods of the Association of Official Analytical Chemists, 17th ed. Published by the Association of Official Analytical Chemists,” Arlington Virginia, U.S.A, 2000.
[34] M. L. Pric, S. Van, L.G. Butler, "A critical evaluation of the vanillin reaction as an assay for tannin in sorghum grain,” J Agric Food Chem., vol. 26, pp.1214-1218, 1978.
[35] V.L. Singleton, R. Orthofer, and R.M. Lamuela- Raventos, "Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteu reagent, In: Packer, L (ed.), Oxidants and antioxidants, part A, " Methods Enzymology, vol. 299, Academic Press, New York, pp.152-178, 1999.
[36] S. Reitman, and S. Frankel, "Colorimetric method for aspartate and alanine transferase,” Am. J. Clin. Pathol., vol. 28, pp.56-63,1957.
[37] A.V. Roy, "Rapid method for determing alkaline phospatase activity in serum with thymoiphthalinmonosphate,” J. Clin. Chem., vol.16, pp.431-436, 1970.
[38] .T. Doumas, W.A. Watson, and H.G. Biggs, "Albumin standards and measurements of serum albumin with bromcresol green,” Clin. Chim. Acta., vol. 31, pp. 87-92, 1971.
[39] A.G. Gornall, C.J. Bardawill, and M.M. David, "Determination of serum proteins by means of the Biuret reaction,” J. Biol. Chem., vol.177, pp. 75-79, 1949.
[40] K. Satoh, "Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method Cline,” Chime. Act. Vol.90, pp.37-43, 1978.
[41] D.E. Paglia, and W.N. Valentine, "Studies on the quantitative and qualitative characterization of erythrocyte gluthione peroxidase,” J. Lab. Clin. Med., vol.70, pp.158-169, 1967.
[42] SAS/STAS, "User's Guide, Statistical analysis system institute, Cary, NC,” 1990.
[43] R. S. Ahmed, V. Seth, S. T. Pasha, and B. D. Banerjee, "Influence of dietary ginger (Zingiber officinals Rosc) on oxidative stress induced by malathion in rats,” Food Chem. Toxicol., vol. 38, no. 200, pp. 443-450, 2000.
[44] A. Zohair, "Protective effect of molokhia (Corchorus olitorius, L.) on malathion-induced hepatotoxicity in rats,” J. Agric s. Sci. Univ., vol.31, pp. 6111-6121, 2006.
[45] C.C. Hsu, C.C. Lin, T.S. Liao, and M. C. Yin, "Protective effect of -allyl cysteine and s-propyl cycteine on acetaminophen-induced hepatotoxicity in mice,” Food and Chemical Toxicology, vol.44, pp.393-397, 2006.
[46] M. Attia Ahmed, and M. Hoda Nasr, "Dimethoate-induced changes in biochemical parameters of experimental rat serum and its neutralization by black seed (Nigella Sativa) oil,” Slovak J. Anim. Sci., vol.42, no.2, pp.87–94, 2009.
[47] M. A. El-Damaty El-Sayed, H. Abdel-Razik Farrag, G. Rowayshed, and M. Hany Fahmy, "Biochemical and Histopathological Effects of Systemic Pesticides on Some Functional Organs of Male Albino Rats,” J. of Applied Sciences Research, vol.8, no.11, pp.5459-5469, 2012.
[48] I.S. Ashoush, O.I. El-Batawy, and G.A. El-Shourbagy, "Antioxidant activity and hepatoprotective effect of pomegranate peel and whey powders in rats,” Annals of Agricultural Science, vol. 5, vol. 4, pp. 334–343, 2013.
[49] Takeo, "Affinity electrophoresis” In: Advanced electrophoresis, Edit. Chrambach, A; Dunn, MJ and Radola, BJ, vol.1 VCH Publisher, Germany,” 1987.
[50] S. G. Yeragi, A. M .Rana, and V. A. Koli, "Effect of pesticides on protein metabolism of mudskipper Boleophthalmus Dussumieri,” J. Ecotoxicol. Environ. Monit. vol. 13, no. 2, pp. 211-214, 2003.
[51] M. Bhadauria, S. K .Nirala, and S. Shukla, "Hepato-protective efficacy of propolis extract: A biochemical and histopathological approach Iranian,” J. of Pharmacology & Therapeutics, vol.6, pp.145-154, 2007.
[52] H.S. Parmar, and A. Kar, "Protective role of Citrus sinensis, Musa paradisiacal, and punica granatum peels against diet–induced atherosclerosis and thyroid dysfunctions in rats,” Nutrition Research, vol. 27, pp.710-718, 2007.
[53] G. Wu, S. Fang Yun-Zhong, J.R. Yang Lupton, and N.D. Turner, "Glutathione metabolism and its implication for health, The American Society for Nutritional Sciences,” J. Nutr., vol.134, pp. 480-492, 2004.
[54] D. Jasprica, A. Mornar, , Z. Debeljak, A. Smoteie-Bubato, M. Medfc-Saric, L. Mayer, Z. Romic, K. Bucan, T. Balog, S. Sobocanec, and V. Sverko, "In vivo study of propolis supplementation effects on antioxidative status and red blood cells,” J. Ethnopharmacol, vol. 110, pp.548-554, 2007.
[55] O. Althunibat, A. Al-Mustafa, K. Tarawneh, K. Khleifat, B. Ridzwan, and H. Qaralleh, "Protective role of Punica granatum L. peel extract against oxidative damage in experimental diabetic rats,” Process Biochemistry, vol.45, pp.581–585, 2010.
[56] M.L. Urso, and P.M. Clarkson, "Oxidative stress, exercise and antioxidant supplementation,” Toxicology, vol.189, pp. 41-54, 2003.
[57] M. Laguerre, J. Lecomte, and P. Villeneuve, "Evaluation of the ability of antioxidants to counteract lipid oxidation: existing methods, new trends and challenges,” Progress in Lipid Research, vol.46, pp.244-282, 2007.
[58] M. Aviram, "Polyphenols from pomegranate juice, red wine, and licorice root protect against lipids peroxidation and attenuate cardiovascular diseases, in: S. Martens, D. Treutter, G. Forkmann (Eds.)"polyphenols 2000,"Proc.XXInt.Conf.polyphenols, 2002.
[59] S.U. Mertens-Talcott, P. Jilma-Stohlawetz, J. Rios, L. Hingorani, and H. Derendorf, "Absorption, metabolism, and antioxidant effects of pomegranate (Punica granatum L.) polyphenols after ingestion of a standardized extract in healthy volunteers,” J. Agric. Food Chem., vol.54, pp.8956–8961, 2006.
[60] M. Viuda-Martos, J. Fernández-López, and J.A. Pérez-Álvarez, "Pomegranate and Many Functional Components as Related to Human Health: A Review,” Comprehensive Reviews in Food Science and Food Safety, Vol.9, no.6, pp.635-654, ISSN 1541-4337, 2010.
[61] A. Al-Jarallah, F. Igdoura, A. Zhang, C. Tenedero, E. White, and M. MacDonald, "The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice,” Atherosclerosis xxx, 1e10, 2013.
@article{"International Journal of Biological, Life and Agricultural Sciences:68155", author = "Abou-Baker Salim and A. A. K. Abou-Arab and Sherif R. Mohamed and T. A. Eldesouky", title = "Influence of Pomegranate (Punica granatum L.) on Dimethoate Induced Hepatotoxicity in Rats", abstract = "Pomegranate (Punica granatum L.) is an ancient fruit of great medical interest and rich source of antioxidants. Pesticides as dimethoate play a crucial role in the occurrence many diseases in plants, animal and human. Therefore the ability of Pomegranate (Punica granatum L.) to alleviate hepatotoxicity induced by organophosphate pesticide dimethoate was investigated. Albino male rats were divided randomly into 4 groups and kept at 7 animals per group in an environmentally controlled condition for 6 weeks. The first group was served as a control group (basal diet), the second group fed on basal diet supplemented with 5% freeze dried pomegranate seeds, the third group fed on 20 ppm dimethoate contaminated diet and the last group fed on dimethoate contaminated diet supplemented with 5% freeze dried pomegranate seeds. The results revealed that administration of dimethoate caused high significant increased in liver functions: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activities as well as lipid peroxide (malonaldhyde, MDA); on the other hand high significant decreased on glutathione (GSH), glutathione peroxidase (GPx), albumin and total protein were observed. However addition of 5% freeze dried pomegranate seeds significantly improved all previously mentioned parameters. These results indicate the dimethoate induced hepatotoxicity and highlight the protective effect of pomegranate seeds as a potential protective agent against dimethoate induced hepatotoxicity. This may be attributed to the powerful antioxidants (polyphenols, total phenols, and total flavonoids) which present in high levels in pomegranate as well as improving the immunity by activation of antioxidant enzymes GSH and GPx.
", keywords = "Pomegranate, organophosphate pesticides, dimethoate, liver toxicity, free radicals, antioxidants.", volume = "8", number = "8", pages = "925-6", }
