Issue
Effect of pomegranate (Punica granatum L.) juice on kidney, liver, heart and testis histopathological changes, and the tissues lipid peroxidation and antioxidant status in lead acetate-treated rats
Corresponding Author(s) : D. S. Aksu
Cellular and Molecular Biology,
Vol. 63 No. 10: Issue 10
Abstract
Pomegranate juice (PJ) contains relevant amounts of active biological compounds which alleviate the detrimental effects of chronic heavy metal exposure. This study investigated the protective potential of PJ against lead-induced oxidative stress. A total of forty adult male Sprague Dawley rats were divided into four experimental groups. The animals were fed a standard pellet diet and tap water ad libitum. The rats were divided into four groups (n=10 for each group): control, lead asetat (2000 ppm), low-treated PJ- a daily dose of 2.000 ppm lead plus 30µl pomegranate juice (included 1.050 µmol total polyphenols, gallic acid equivalent), and high-treated PJ- a daily dose of 2.000 ppm lead plus 60µl pomegranate juice (included 2.100 µmol total polyphenols, gallic acid equivalent). The treatments were delivered for 5 weeks. After the treatment period, the tissues samples (kidney, liver, heart and testis) were collected. Tissue lead (Pb) and mineral amounts (copper, zinc, and iron), tissues lipid peroxidation level and antioxidant status, and tissues histopathological changes were determined. The results showed that the highest rate lead loading was in the kidney and the testis. Pomegranate juice was decreased the lead levels of soft tissues examined; increased Zn amounts in tissues of which the lead accumulation was higher (kidney and the testis); decreased the copper, zinc and the iron levels of the liver and heart tissues, without creating a weakness in antioxidant capacity of these tissues, restricted the oxidative stress by decreasing lipid peroxidation, improved both of the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalaz (CAT), and the level of glutathione (GSH) in all the tissues examined in lead-treated groups. As histopathological findings, the cellular damage induced by lead in the tissues of the kidney, liver and the heart were observed to have been partially prevented by PJ treatment. The protective effect of PJ was more pronounced in the testis compared to those others.
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- Mansouri MT, Cauli O. Motor alterations induced by chronic lead exposure. Environ Toxicol Phar 2009; 27: 307–13. doi:10.1016/j.etap.2009.01.003
- Navarro-Moreno LG, Quintanar-Escorza MA, González S, Mondragón R, Cerbón-Solorzáno J, Valdés J, Calderón-Salinas JV. Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells. Toxicol in Vitro 2009; 23: 1298–1304. doi:10.1016/j.tiv.2009.07.020
- Abdou HM, Hassan MA. Protective role of omega-3 polyunsaturated fatty acid against lead acetate-induced toxicity in liver and kidney of female rats. Biomed Res Int. 2014; 1-11. doi:10.1155/2014/435857
- Kolawole TA, Dapper DV, Ojeka SO. Ameliorative effects of the methanolic extract of the rind of citrullus lanatus on lead acetate induced toxicity on semen parameters and reproductive hormones of male albino wistar rats. European J Med Plants 2014; 4 (9): 1125-37. doi:10.9734/EJMP/2014/11011
- Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stres. Part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001; 1: 529-39. doi:10.2174/1568026013394831
- Noriega GO, Tomaro ML, del Batlle AM. Bilirubin is highly effective in preventing in vivo δ-aminolevulinic acid-induced oxidative cell damage. Biochim Biophys Acta 2003; 638: 173-8. doi.org/10.1016/S0925-4439(03)00081-4
- Alonso ML, Montaña FP, Miranda M, Castillo C, Hern´andez J, Benedito JL. 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 2004; 17: 389-97. doi:10.1023/B:BIOM.0000029434.89679.a2
- Flora SJS, Mittal M, Mehta A. Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 2008; 128: 501-23.
- Leonard SS, Harris GK, Shi XL. Metal-induced oxidative stress and signal transduction. Free Rad Biol Med 2004; 37: 1921-42.doi: 10.1016/j.freeradbiomed.2004.09.010
- Lowry JA. Oral chelation therapy for patients with lead poisoning. American AcademyofPediatrics.http://www.who.int/selection_medicine/committees/expert/18/applications /4_2Lead. Oral Chelators.pdf. ( accessed 16.25.11)
- Saxena G, Flora SJS. Lead induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a Thiol chelator in rats. J Biochem Mol Toxic 2004; 18 (4): 221-33.doi: 10.1002/jbt.20027.
- Aksu DS, Didin M, Kayıkçı F. The protective role of polyphenols on blood cells in rats exposed to lead. Rev Romana Med Lab 2012; 20 (3/4):47-57
- Aksu DS, Sağlam YS, Aksu T. The investigation of neuroprotective effects of pomegranate juice against low level lead induced oxidative stress in rats brain. Eurasian J Vet Sci 2016; 2(4): 255-59. doi: 10.15312/EurasianJVetSci.2016422397
- Espín JC, García-Conesa MT, Tomás-Barberán FA. Nutraceuticals: facts and fiction. Phytochemistry 2007; 68: 2896–3008.doi: 10.1016/j.phytochem.2007.09.014
- Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109:177–206.doi: 10.1016/j.jep.2006.09.006
- Seeram NP, Aviram M, Zhang Y, Henning SM, Feng L, Dreher M, Heber D. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J Agric Food Chem 2008; 56: 1415–22.doi: 10.1021/jf073035s
- Gill MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000; 48: 4581–89.doi: 10.1021/jf000404a
- Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 2005; 174:386–93.doi: 10.1097/01.ju.0000161209.39959.67
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- Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules 2010; 15: 7792-814.doi: 10.3390/molecules15117792
- Guo C, Wei J, Yang J, Xu J, Pang W, Jiang Y. Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. Nutr Res 2008; 28:72-7.doi: 10.1016/j.nutres.2007.12.001
- Ranganna S. Sugar estimation. In: Handbook of analysis and quality control for fruit and vegetable products. Ranganna S. (ed.), 2nd edn. Tata McGraw-Hill, New Delhi, 2001, pp 12-17
- Ruck JA. Chemical methods of analysis of fruits and vegetables. Dep Agri Canada Publication No. 1154, Canada, 1963.
- Giusti MM and Wrolstad RE. Characterization and measurement of anthocyanins by UV–visible spectroscopy. In: Current protocols in food analytical chemistry. Wrolstad RE and Schwartz SJ (eds.) John Wiley and Sons, New York, 2001, pp 1–13
- Ough CS and Amerine MA Methods for analysis of musts and wines. A Wiley Inter-Science Publication, New York, 1998.
- Cuendet M, Hostettmann K, Potterat O. Iridoid glucosides with free radical scavenging properties from fagraea bluemi. Helvetica Chim Acta 1997; 80: 1144-52.doi: 10.1002/hlca.19970800411
- Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice. Am J Clin Nutr 2000; 71: 1062–76.
- Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, Aviram M. Pomegranate juice supplementation to atherosclerotic mice redu ces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr 2001; 131(8): 2082-89.
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- Yoshoiko T, Kawada K, Shimada T. Lipid peroxidation in maternal and cord blood and protective mechanism againist active-oxygen toxicity in the blood. American J Obstet Gynecol 1979; 135:372-376.doi: 10.1016/0002-9378(79)90708-7
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- Sedlak J, Lindsay RH. Estimation of total protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1967; 25: 192-205.doi: 10.1016/0003-2697(68)90092-4
- Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121-6.
- Sun Y, Oberley LW, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
- Ergün G, Aktaş S. Comparisons of sum of squares methods in ANOVA Models. Kafkas Univ Vet Fak Derg 2009; 15 (3):481-4.doi: 10.9775/kvfd.2009.213
- SAS: SAS/STAT. User's Guide. Release 6.08 ed., SAS. Institute Inc, Cary, North Carolina, USA, 1994.
- Cam M, Hisil Y, Durmaz G. Classification of eight pomegranate juices based on antioxidant capacity measured by four methods. Food Chem 2009; 112: 721–6. doi:10.1016/j.foodchem.2008.06.009
- Akhavan H, Barzegar M, Weidlich H, Zimmermann BF. Phenolic compounds and antioxidant activity of juices from ten Iranian pomegranate cultivars depend on extraction. Chemist 2015; 1-7. doi:10.1155/2015/907101
- Arslan H, Saripinar-Aksu D, Ozdemir S, Yavuz O, Or ME, Barutcu UB. Evaluation of the relationship of blood heavy metal, trace element levels and antioxidative metabolism in cattle which are living near the trunk roads. Kafkas Univ Vet Fak Derg 17 (Suppl A) 2011; 77-82. doi:10.9775/kvfd.2010.3433
- Gupta RC. Veterinary Toxicology. Basic and clinical principles, 2 nd edn. Academic Press in an Imprint of Elsevier, London, 2012.
- Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology 2007; 148 (6):2663-8.doi: 10.1210/en.2006-1331
- Kwong WT, Friello P, Semba RD. Interactions between iron deficiency and lead poisoning: epidemiology and pathogenesis. Sci Total Environ 2004; 330 (1-3): 21-37.doi: 10.1016/j.scitotenv.2004.03.017
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- Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011; 117 (17): 4425-33.doi: 10.1182/blood-2011-01-258467
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References
Mansouri MT, Cauli O. Motor alterations induced by chronic lead exposure. Environ Toxicol Phar 2009; 27: 307–13. doi:10.1016/j.etap.2009.01.003
Navarro-Moreno LG, Quintanar-Escorza MA, González S, Mondragón R, Cerbón-Solorzáno J, Valdés J, Calderón-Salinas JV. Effects of lead intoxication on intercellular junctions and biochemical alterations of the renal proximal tubule cells. Toxicol in Vitro 2009; 23: 1298–1304. doi:10.1016/j.tiv.2009.07.020
Abdou HM, Hassan MA. Protective role of omega-3 polyunsaturated fatty acid against lead acetate-induced toxicity in liver and kidney of female rats. Biomed Res Int. 2014; 1-11. doi:10.1155/2014/435857
Kolawole TA, Dapper DV, Ojeka SO. Ameliorative effects of the methanolic extract of the rind of citrullus lanatus on lead acetate induced toxicity on semen parameters and reproductive hormones of male albino wistar rats. European J Med Plants 2014; 4 (9): 1125-37. doi:10.9734/EJMP/2014/11011
Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stres. Part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001; 1: 529-39. doi:10.2174/1568026013394831
Noriega GO, Tomaro ML, del Batlle AM. Bilirubin is highly effective in preventing in vivo δ-aminolevulinic acid-induced oxidative cell damage. Biochim Biophys Acta 2003; 638: 173-8. doi.org/10.1016/S0925-4439(03)00081-4
Alonso ML, Montaña FP, Miranda M, Castillo C, Hern´andez J, Benedito JL. 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 2004; 17: 389-97. doi:10.1023/B:BIOM.0000029434.89679.a2
Flora SJS, Mittal M, Mehta A. Heavy metal induced oxidative stress and its possible reversal by chelation therapy. Indian J Med Res 2008; 128: 501-23.
Leonard SS, Harris GK, Shi XL. Metal-induced oxidative stress and signal transduction. Free Rad Biol Med 2004; 37: 1921-42.doi: 10.1016/j.freeradbiomed.2004.09.010
Lowry JA. Oral chelation therapy for patients with lead poisoning. American AcademyofPediatrics.http://www.who.int/selection_medicine/committees/expert/18/applications /4_2Lead. Oral Chelators.pdf. ( accessed 16.25.11)
Saxena G, Flora SJS. Lead induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a Thiol chelator in rats. J Biochem Mol Toxic 2004; 18 (4): 221-33.doi: 10.1002/jbt.20027.
Aksu DS, Didin M, Kayıkçı F. The protective role of polyphenols on blood cells in rats exposed to lead. Rev Romana Med Lab 2012; 20 (3/4):47-57
Aksu DS, Sağlam YS, Aksu T. The investigation of neuroprotective effects of pomegranate juice against low level lead induced oxidative stress in rats brain. Eurasian J Vet Sci 2016; 2(4): 255-59. doi: 10.15312/EurasianJVetSci.2016422397
Espín JC, García-Conesa MT, Tomás-Barberán FA. Nutraceuticals: facts and fiction. Phytochemistry 2007; 68: 2896–3008.doi: 10.1016/j.phytochem.2007.09.014
Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109:177–206.doi: 10.1016/j.jep.2006.09.006
Seeram NP, Aviram M, Zhang Y, Henning SM, Feng L, Dreher M, Heber D. Comparison of antioxidant potency of commonly consumed polyphenol-rich beverages in the United States. J Agric Food Chem 2008; 56: 1415–22.doi: 10.1021/jf073035s
Gill MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 2000; 48: 4581–89.doi: 10.1021/jf000404a
Azadzoi KM, Schulman RN, Aviram M, Siroky MB. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 2005; 174:386–93.doi: 10.1097/01.ju.0000161209.39959.67
Rosenblat M, Aviram M. In: Pomegranates: Ancient Roots to Modern Medicine, Antioxidative Properties of Pomegranate: In vitro studies. Seeram NP, Heber D. (eds.) Taylor and Francis Group, New York, 2006, pp 31–43
Kelsey NA, Wilkins HM, Linseman DA. Nutraceutical antioxidants as novel neuroprotective agents. Molecules 2010; 15: 7792-814.doi: 10.3390/molecules15117792
Guo C, Wei J, Yang J, Xu J, Pang W, Jiang Y. Pomegranate juice is potentially better than apple juice in improving antioxidant function in elderly subjects. Nutr Res 2008; 28:72-7.doi: 10.1016/j.nutres.2007.12.001
Ranganna S. Sugar estimation. In: Handbook of analysis and quality control for fruit and vegetable products. Ranganna S. (ed.), 2nd edn. Tata McGraw-Hill, New Delhi, 2001, pp 12-17
Ruck JA. Chemical methods of analysis of fruits and vegetables. Dep Agri Canada Publication No. 1154, Canada, 1963.
Giusti MM and Wrolstad RE. Characterization and measurement of anthocyanins by UV–visible spectroscopy. In: Current protocols in food analytical chemistry. Wrolstad RE and Schwartz SJ (eds.) John Wiley and Sons, New York, 2001, pp 1–13
Ough CS and Amerine MA Methods for analysis of musts and wines. A Wiley Inter-Science Publication, New York, 1998.
Cuendet M, Hostettmann K, Potterat O. Iridoid glucosides with free radical scavenging properties from fagraea bluemi. Helvetica Chim Acta 1997; 80: 1144-52.doi: 10.1002/hlca.19970800411
Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E–deficient mice. Am J Clin Nutr 2000; 71: 1062–76.
Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, Aviram M. Pomegranate juice supplementation to atherosclerotic mice redu ces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr 2001; 131(8): 2082-89.
ć°lhan F, Vural SA, Yıldırım S, Sözdutmaz ć°, Alcigir ME. Expression of p53 protein, Jaagsiekte sheep retrovirus matrix protein, and surfactant protein in the lungs of sheep with pulmonary adenomatosis. J Vet Diagn Invest 2016; 28 (3): 249-56. doi:10.1177/1040638716636939
Hoshino J, Mise K, Ueno T, Imafuku A, Kawada M, Sumida K, Hiramatsu R, Hasegawa E, Yamanouchi M, Hayami N, Suwabe T, Sawa N, Hara S, Fujii T, Ohashi K, Ubara Y, Takaichi K. A pathological scoring system to predict renal outcome in diabetic nephropathy. Am J Nephrol 2015; 41: 337-344. doi:10.1159/000431333
Yoshoiko T, Kawada K, Shimada T. Lipid peroxidation in maternal and cord blood and protective mechanism againist active-oxygen toxicity in the blood. American J Obstet Gynecol 1979; 135:372-376.doi: 10.1016/0002-9378(79)90708-7
Mertens D. AOAC Official Method 922.02. In: Horwitz W and Latimer GW (eds) Preparation of laboratuary sample. Official methods of analysis, Chapter 3. Eighteenth ed. AOAC-International Suite 500,481. Maryland: North Frederick Avenue, 20877-2417, Gaitherburg, (2005a) pp 1-2
Mertens D. AOAC official method 975.03. In: Horwitz W and Latimer GW (eds) Metal in plants and pet foods. Official methods of analysis Chapter 3. Eighteenth ed., AOAC-International Suite 500, 481. Maryland: North Frederick Avenue, 20877-2417, Gaitherburg, (2005b) pp 3-4
Sedlak J, Lindsay RH. Estimation of total protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1967; 25: 192-205.doi: 10.1016/0003-2697(68)90092-4
Aebi H. Catalase in vitro. Methods Enzymol 1984; 105:121-6.
Sun Y, Oberley LW, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
Ergün G, Aktaş S. Comparisons of sum of squares methods in ANOVA Models. Kafkas Univ Vet Fak Derg 2009; 15 (3):481-4.doi: 10.9775/kvfd.2009.213
SAS: SAS/STAT. User's Guide. Release 6.08 ed., SAS. Institute Inc, Cary, North Carolina, USA, 1994.
Cam M, Hisil Y, Durmaz G. Classification of eight pomegranate juices based on antioxidant capacity measured by four methods. Food Chem 2009; 112: 721–6. doi:10.1016/j.foodchem.2008.06.009
Akhavan H, Barzegar M, Weidlich H, Zimmermann BF. Phenolic compounds and antioxidant activity of juices from ten Iranian pomegranate cultivars depend on extraction. Chemist 2015; 1-7. doi:10.1155/2015/907101
Arslan H, Saripinar-Aksu D, Ozdemir S, Yavuz O, Or ME, Barutcu UB. Evaluation of the relationship of blood heavy metal, trace element levels and antioxidative metabolism in cattle which are living near the trunk roads. Kafkas Univ Vet Fak Derg 17 (Suppl A) 2011; 77-82. doi:10.9775/kvfd.2010.3433
Gupta RC. Veterinary Toxicology. Basic and clinical principles, 2 nd edn. Academic Press in an Imprint of Elsevier, London, 2012.
Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H. The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology 2007; 148 (6):2663-8.doi: 10.1210/en.2006-1331
Kwong WT, Friello P, Semba RD. Interactions between iron deficiency and lead poisoning: epidemiology and pathogenesis. Sci Total Environ 2004; 330 (1-3): 21-37.doi: 10.1016/j.scitotenv.2004.03.017
Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. Biochimica et Biophysica Acta 2012; 1823:1434–43.doi: 10.1016/j.bbamcr.2012.01.014
Ganz T. Hepcidin and iron regulation, 10 years later. Blood 2011; 117 (17): 4425-33.doi: 10.1182/blood-2011-01-258467
Oteiza PI. Zinc and the modulation of redox homeostasis. Free Radic Biol Med 2012; 53(9): 1748–59. doi:10.1016/j.freeradbiomed.2012.08.568.
Carpene E, Andreani G, Isani G. Metallothionein functions and structural characteristics. J Trace Elem Med Biol 2007; 21: 35–9. doi: 10.1016/j.jtemb.2007.09.011
David MP, Valentí£o P, Pereira JA, Paula B. Andrade PB. Phenolics: from chemistry to biology. Molecules 2009; 14:2202-11. doi:10.3390/molecules14062202
Prousek J. Fenton chemistry in biology and medicine. Pure Appl Chem 2007; 79:2325–38.doi: 10.1351/pac200779122325
Kambe T, Tsuji T, Hashimoto A, Itsumura N. The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Phys Rev 2015; 95:749-84. doi: 10.1152/physrev.00035.2014
Jomova K, Valko M. Advances in metal-induced oxidative stress and human disease. Toxicol 2011; 283: 65–87.doi: 10.1016/j.tox.2011.03.001
Cremers CM, Jacob U. Oxidant sensing by reversible disulfide bond formation. J Biol Chem 2013; 288 (37): 26489–96. doi: 10.1074/jbc.R113.462929
Yuan G, Dai S, Yin Z, Lu H, Jia R, Xu J et al. Sub-chronic lead and cadmium co-induce apoptosis protein expression in liver and kidney of rats. Int J Clin Exp Pathol 2014; 7 (6): 2905–14.
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