Therapeutic effects of pomegranate (Punica granatum) pith and carpellary membrane extract on lead-induced toxicity in rats

Document Type : Research Articles


1 University of Shahrekord

2 Urmia University

3 Ferdowsi University of Mashhad

4 University of Urmia


Pomegranate is an ancient edible fruit with various pharmaceutical bioactivities such as antioxidant, lipid regulation and anti-inflammation. In this study the effectiveness of pomegranate pith and carpellary membrane (PPCM) extract in treatment of experimental lead intoxication was assessed in rats. Female Wistar rats were exposed to 1000ppm lead acetate in drinking water for 35 days and treated thereafter with PPCM extiract (100 and 200mg/kg, orally) twice a day for 35 days. The concentration of lead in blood, kidney, liver, bone and brain were measured using atomic absorption spectrophotometry. Treatment with PPCM extract reduced lead retention in blood and tissues. With the highest dose of PPCM extract, the greatest rate of reduction of lead concentrations were observed in brain (61%), blood (53%), and bone (34.5%). No significant changes were observed in copper, zinc and iron concentration of serum and liver, in neither doses of PPCM extract. In conclusion it was demonestrated that PPCM and carpellary membrane had therapeutic effect in the treatment of lead intoxication without any side effects on essential elements in blood and tissues of rats.


Ahmed, M. and Siddiqui, M. (2007). Low level lead exposure and oxidative stress: current opinions. Clinica Chemica Acta, 383, 57-64.
Aksu, D.S., Didin, M. and Kayikci, F. (2012). The protective role of polyphenols on blood cells in rats exposed to lead. Revista Român ăde Medicinăde Laborator, 20, 233-243.
Alabbassi, M.G. and Hussain, S.A. (2008). Therapeutic Effects of Melatonin in Lead-Induced Toxicity in Rats. Iranian Journal of pharmaceutical Research, 17, 47-54.
Alcaraz-Contreras, Y.L., Garza-Oca˜nas, L., Carca, K. and Ram, S. (2011). Effect of Glycine on LeadMobilization, Lead-Induced Oxidative Stress, and Hepatic Toxicity in Rats. Journal of Toxicology, doi: 10.1155/2011/43.539
Alonso, M.L., Montana, F.P., Miranda, M., Castillo, C., Hernandez, J. and Benedito, J.L. (2004). Interactions between toxic (As, Cd, Hg and Pb) and nutritional essential (Ca, Co, Cr, Cu, Fe, Mn, Mo, Ni, Se, Zn) elements in the tissues of cattle from NW Spain. BioMetals, 17, 389-397.
Anderson, B.O. and Adenuga, G.A. (2007). Effect of lead exposure on liver lipid peroxidative and antioxidant defense systems of protein-undernourished rats. Biological Trace Element Research, 116, 219–225.
Anderson, O. (1999). Principles and recent developments in chelation treatment of metal intoxication. Chemical Reviews, 99, 2683–2710.
Antonio-Garcia, M. and Masso-Gonzalez, E. (2008). Toxic effects of perinatal lead exposure on the brain of rats: Involvement of oxidative stress and the beneficial role of antioxidants. Food and Chemical Toxicology, 46, 2089-2095.
Arrak, J.K., (2010). Effect of Ellagic Acid Extracted from Pomegranate (Punica granatum L.) on Thyroid and Parathyroid Gland of Adult Rats Exposed to Lead Acetate. Kufa Journal For Veterinary Medical Sciences, 1, 39-51.
Aslani, M., Najarnezhad, V. and Mohri, M. (2009). Individual and Combined Effect of Meso-2,3-Dimercaptosuccinic Acid and Allicin on Blood and Tissue Lead Content in Mice. Planta Medica, 76, 241-244.
Aslani, M.R., Najarnezhad, V. Mohri, M., and Azad, M. (2011). The effect of allicin on blood and tissue lead content in mice. Comparative Clinical Pathology, 20, 121-125.
Bhandari, P.R. (2012). Pomegranate (Punica granatum L). Ancient seeds for modern cure? Review of potential therapeutic applications. Internatial Journal of nutrition Pharmacology Neurological Diseases, 2, 171-184.
Casteel, S.W. (2006). Lead. Small Animal Toxicology. M. E. Peterson and P. A. Talcott. Louis, Saunders, 795–805.
Cory-Slechta, D.A., Weiss, B. and Cox, C. 1987. Mobilization and redistribution of lead over the course of calcium distribution of lead over the course of calcium disodium ethylenediaminetetra acetate chelation therapy. Journal of Pharmacology and Experimental Therapeuties, 243, 804–813.
Domingo, J. (1998). Developmental toxicity of metal chelating agent. Reproductive Toxicology, 12, 499-510.
El-Ashtoukhy, E.Z., Amin, N.K. and Abdelwahab, O. (2008). Removal of lead (II) and copper (II) from aqueous solution using pomegranate peel as a new adsorbent. Desalination, 223, 162-173.
Grandjean, P. (1978). Regional distribution of lead in human brains. Toxicology Letters, 2, 65-69.
Gurer, H. and Ercal, N. (2000). Can antioxidants be beneficial in the treatment of lead poisoning? Free Radical Biology and Medicine, 29, 927-945.
Gwaltney-Beant, S. (2003). Lead. Clinical Veterinary Toxicology. K. H. Plumlee. Louis, Mosby, S.t. 204–210.
Haidari, M., Ali, M. and Cabrini, R.L. (2009). Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir. Phytomedicine, 16, 1127-1136.
Hsu, P. and Guo, Y. (2002). Antioxidant nutrient and lead toxicity. Toxicology, 180, 33-44.
Huang, T.H., Peng, G., Prasad Kota, B., Qian Li, G., Yamahara, J., Roufogalis, B.D. and Li, Y. (2005). Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. British Journal of Pharmacology, 145, 767–774.
Jakubowski, M. (2011). Low-level environmental lead exposure and intellectual impairment in children- the current concepts of risk assessment. International Journal of occupational Medicine and Environmental Health, 24, 1-7.
Jasuja, N.D. and Saxena, R. (2012). Pharmacological Characterization and Beneficial Uses of Punica granatum. Asian Journal of Plant Sciences, 11, 251-267.
Jones, M.M., Singh, P.K., Kostial, K., Blanus, M., Piasek, M. and Restek-Samarozija, N. (1997). Comparative in vivo lead mobilization of meso- and rac-2,3-dimercaptosuccinic acids in albino Wistar rats. Pharmacol Toxicol, 80, 182–186.
Jurenka, J. (2008). Therapeutic applications of pomegranate (Punica granatumL.): a review. Alternative Medicine Review, 13, 128-144.
Kalia, K. and Flora, S. (2005). Strategies for safe and effective therapeutic measures for chronic arsenic and lead poisoning. Journal of Occupational Health, 47, 1-21.
Khan, M.S.H., Mostofa, M., Jahan, M.S., Sayed, M.A. and Hossain, M.A. (2008). Effect of garlic and vitamin B-complex in lead acetate induced toxicosis in mice. Bangladesh Journal of Veterinary Medicine, 6, 203–210.
Kilikdar, D., Mukherjee, D., Mitra, E., Ghosh, A.K., Basu, A., Chandra M. and Bandyoapdhyay, D. (2011). Protective effect of aqueous garlic extract against lead-induced hepatic injury in rats. Indian Journal of Experimental Biology, 49, 498-510.
Klaassen, C.D., Liu, J. and Choudhuri, S. (1999). Metallothionein: an intracellular protein to protect against cadmium tox-icity. Annual Review of Pharmacology and Toxicology, 39, 267-294.
Kosnett, M. (2001). Lead. Clinical Toxicology. M. Ford, K. Delaney, L. Louis and T. Erickson. Philadelphia, Saunders.
DG, L.I., Zhang, Z.M. and Chen, X.J. (2003). Study on the influence of aqueous extract of leaves of punica granatum on the secretion of gastric acids and exprimental gastric ulcer. Chinese Journal of Preventive Medicine, 19, 23-24.
Meldrum, J.B. and Kok, W. (2003). Effects of calcium disodium EDTA and meso-2, 3-dimercaptosuccinic acid of tissue concentrations of lead for use in treatment of calves with experimentally induced lead toxicosis. American Journal of Veterinary Research, 6, 672–676.
Najar-Nezhad, V., Aslani, M.R. and Balali-Mood, M. (2008). Evaluation of Allicin for the Treatment of Experimentally Induced Subacute Lead Poisoning in Sheep. Biological Trace Element Research, 126, 141-147.
Needleman, H. (2009). Low level lead exposure: History and discovery. Annals of Epidemiology, 19, 235-238.
Osman, M., Ahmed, M., Mahfouz, S. and Elaby, S. (2011). Biochemical Studies on The Hepatoprotective Effects of Pomegranate and Guava Ethanol Extracts. New York Science Journal, 4, 27-39.
Patra, R.C. and Swarup, D. (2004). Effect of antioxidant ascorbic acid, l-methionine or α tocopherol alone or along with chelator on cardiac tissue of lead-treated rats. Veterinarski arhiv, 74, 235-244.
Patrick, L. (2006a). Lead toxicity, a review of the literature. Part I: Exposure, evaluation, and treatment. Alternative Medicine Review, 11, 2-22.
Patrick, L. (2006b). Lead toxicity. Part II: The role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity. Alternative Medicine Review, 11, 114-126.
Petit, T.L., Alfano, D.P. and LeBoutillier, J.C. (1983). Early lead exposure and the hippocampus, a review and recent advances. Neurotoxicology, 4, 79-94.
Shiban, M.S., Al-Otaibi, M. and Al-Zoreky, N.S. (2012). Antioxidant Activity of Pomegranate (Punica granatumL.) Fruit Peels. Food and Nutrition Sciences, 3, 991-996.
Taubeneck, M.W., Domingo, J.L., Liobet, J.M. and Keen, C.L. (1992). Meso-2, 3-dimercaptosuccinic acid (DMSA) affects maternal and fetal copper metabolism in Swiss mice. Toxicology, 72, 27-40.
Tendon, S.K., Singh, S. and Jain, V.K. (1994). Efficacy of combined chelation in lead intoxication. Chemical Research in Toxicology, 7, 585–589.
Thuppil, V. and Kaushik, V.S. (2012). Future of Lead Chelation – Distribution and Treatment. Journal of Krishna Institute of Medical Sciences University, 1, 6-23.
Wang, R., Ding, Y., Rliu, R., Xiang, L. and Du, L. (2010). Pomegranate: Constituents, Bioactivities and Pharmacokinetics. Fruit, Vegetable and Cereal Science and Biotechnology, 4, 77-87.
Zmudzki, J., Bratton, G.R. and Womac, C. (1983). Lead poisoning in cattle: reassessment of the minimum toxic oral dose. Bulletin of Environment Contamination and Toxicology, 30, 435–441.