Özlem Yildiz GÜLAY, Gülşah CANDAN, Mehmet Şükrü GÜLAY

Bisfenol A’ya maruz kalan erkek Yeni Zelanda tavşanlarında punikalajinin potansiyel etkileri

Çalışmada, BPA verilen Yeni Zelanda tavşanlarında punikalajininbazı oksidan-antioksidan enzimler ile bazı biyokimyasal parametreler üzerine olası etkilerin incelendi. Bu amaçla 2 hafta boyunca laboratuvar koşullarına alıştırılan tavşanlar, her grupta 6 tavşan olacak şekilde rastgele 4 gruba ayrıldı: Kontrol (C; mısır yağı ve distile su), BPA (BPA; mısır yağı içerisinde 20 mg/kg BPA ve distile su), punikalajin (PUN; mısır yağı ve distile su içerisinde 2 mg/kg punikalajin), ve BPA-punikalajin grubu (B+P; mısır yağı içerisinde 20 mg/kg BPA ve distile su içerisinde 2 mg/kg PUN). Uygulamalar 9 hafta boyunca günlük olarak yapıldı ve haftada bir kez yapılan tartımlara göre dozlar ayarlandı. Çalışma sonunda alınan kan ve doku örneklerinden hematolojik, biyokimyasal ve oksidanantioksidan parametrelerin ölçümleriyapıldı. Analizler neticesinde plazma bilirubin, albümin ve toplam plazma protein düzeyleri ile Mg, P, Ca, Na, K, seviyelerinde herhangi bir istatistiki farka rastlanmazken, farklı gruplardaki plazma, karaciğer ve böbrek glutatyon peroksidaz değerleri de önemsiz bulundu (p>0,1). Oral BPA uygulamaları serum kolesterol, LDL, HDL, amilaz, lipaz, CRP, GGT seviyeleri ile karaciğer ve böbrek dokusundaki malonildialdehit, katalaz ve süperoksit dismütaz seviyelerini olumsuz etkiledi (p<0,05). B+P grubunda ise bu parametrelerde önemli ölçüde iyileşme gözlendi. Elde edilen sonuçlar, BPA'nın erkek tavşanlarda yol açtığı olasıtoksik etkilerin punikalajin tedavisi ile önemli ölçüde düzeltilebileceğini gösterdi.

Anahtar Kelimeler:

Antioksidanlar, Kolesterol, Oksidan-Antioksidan enzimler, Polifenoller, Toksikasyon

Potential effects of punicalagin on New Zealand White rabbits exposed to bisphenol A

The possible effects of punicalagin on some oxidant-antioxidant enzymes and biochemical parameters in bisphenol A (BPA)-treated rabbits were investigated. Animals were randomly divided into 4 groups, each containing 6 rabbits: Control (C; corn oil and distilled water), BPA (BPA; 20 mg/kg BPA in corn oil and distilled water), the punicalagin (PUN; corn oil and 2 mg/kg punicalagin in distilled water), and BPA-punicalagin (B+P; 20 mg/kg BPA in corn oil and 2 mg/kg PUN in distilled water) groups. Daily treatments continued for 9 weeks and doses were adjusted according to body weights measured for each week. At the end of the study, hematological, biochemical, and oxidant-antioxidant parameters were measured from blood and tissue samples. The difference in the levels of plasma bilirubin, albumin, total plasma protein, Mg, P, Ca, Na, K, and levels of glutathione peroxidase in plasma, liver, and kidney were non-significant (p>0.1). However, oral BPA administration adversely affected serum cholesterol, LDL, HDL, amylase, lipase, CRP, and GGT concentrations. Likewise, malondialdehyde, catalase, and superoxide dismutase levels in the kidney and liver were also negatively altered by BPA (p<0.05). Significant improvements in these parameters were apparent in the B+P group. The data generated here showed that punicalagin possessed a beneficial impact on potentially reducing the possible toxic effects of BPA in rabbits.

Keywords:

Antioxidants, Cholesterol, Oxidant-Antioxidant enzymes, Polyphenols, Toxication,

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Amal AF, Monira AA, Abeer HA.Modulatory effects of pomegranate juice on nucleic acids alterations and oxidative stress in experimentaly hepatitis rats. Life Sci J. 2012; 9(3):676-682.
Andersen JK. Oxidative stress in neurodegeneration: Cause or consequence? Nat Rev Neurosci. 2004; 10(7):S18-S25.
Atrahimovich D, Khatib S, Sela S, Vaya J, Samson AO. Punicalagin induces serum low-density lipoprotein influx to macrophages. Oxid Med Cell Longev. 2016;2016:7124251. doi: 10.1155/2016 /7124251.
Avcı B, Bahadır A, Tuncel OK, Bilgici B. Influence of αtocopherol and α-lipoic acid on bisphenol-A-induced oxidative damage in liver and ovarian tissue of rats. Toxicol Indust Health. 2016; 32(8):1381-1390.
Aviram M, Dornfeld L, Kaplan M, Coleman R, Gaitini D, Nitecki S, Hofman A, Rosenblant M, Volkova N, Presser D, Attias J, Hayek T, Fuhrman B. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp Clin Res. 2002; 28(2-3):49-62.
Aydemir B, Karadağ Sarı E. Antioksidanlar ve büyüme faktörleri ile ilişkisi. Kocatepe Vet J.2009; 2(2): 56-60.
Berger MM. Can oxidative damage be treated nutritionally? Clin Nutr. 2005; 24(2):172-183.
Bukowska B, Kowalska S. Phenol and catechol induce prehemolytic and hemolytic changes in human erythrocytes. Toxicol Letters. 2004; 152(1): 73–84.
Cerdá B, Ceron JJ, Tomás-BarberánFA, Espín JC. Repeated oral administration of high doses of the pomegranate ellagitannin punicalagin to ratsfor 37 days is not toxic. J Agric Food Chem. 2003; 51(11): 3493-3501.
Chitra KC, Latchoumycandane C, Mathur PP. Induction of oxidative stress by bisphenol A in the epididymal sperm of rats. Toxicology. 2003;185, 19-127.
Coballase-Urrutia E, Pedraza-Chaverri J, Cardenas-Rodriguez N, Huerta-Gertrudis B, Edna Garcia-Cruz M, Ramirez-Morales A, Javier Sanchez-Gonzalez D, Maria Martinez-Martinez C, Camacho-Carranza R, JavierEspinosa-Aguirre J. Hepatoprotective effect of acetonic and methanolic extracts of heterotheca inuloides against CCl(4)-induced toxicity in rats. Exp Toxicol Pathol. 2011; 63(4):363-370.
Daidoji T, Inoue H, Kat S, Yokota H.Glucuronidation and excretion of nonylphenol in perfused rat liver. Drug Met Disp. 2003; 31(8): 993-998.
Dodge JA, Glasebrook AL, Magee DE, Phillips DL, Sato M, Short LL, Bryant HU. Environmental estrogens: Effects of cholesterol lowering and bone in the ovariectomized rat. J Steroid Biochem Molec Biol. 1996; 59:155-161.
Geetharathan T, Peera K. Effect of bisphenol-a on the cardiovascular system in pregnant rats. Int J Pharm Sci & Res. 2018; 9(11): 4690-95. doi: 10.13040/IJPSR.0975-8232.9(11).4690-95.
Gil 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(10): 4581-4589.
Haber D, Seeram NP, Wyatt H, Henning SM, Zhang Y, Ogden LG, Dreher M, Hill JO. Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in overweight individuals with increased waist size. J Agric Food Chem. 2007; 55(24): 10050-10054.
Henderson AR, Moss DW. Tietz fundamentals of clinical chemistry. Ed: Burtis, CA, Ashwood ER. Lubbok, Texas, USA. 2005;pp. 352-392.
Jean-Gilles D, Li L, Vaidyanathan VG, King R, Cho B, Worthen DR, Seeram NP. Inhibitory effects of polyphenol punicalagin on type-II collagen degradation in vitro and inflammation in vivo. Chem Biol Interact. 2013; 205(2): 90-99.
Kabuto H, Amakawa M, Shishibori T. Exposure to bisphenol A during embryonic/fetal life and infancy increases oxidative injury and causes underdevelopment of the brain and testis in mice. Life Sci. 2004;74(24): 2931-2940.
Kaplan M, Hayek T, Raz A, Coleman R, Dornfeld L, Vaya J, Aviram M.Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr. 2001; 131(8): 2082-2089.
Karabulut H, Gulay MS. Free radicals. Mehmet Akif Ersoy Ü Sağ Bil Enst Dergisi. 2016a; 4(1): 50-59.
Karabulut H, Gulay MS.Antioxidants . Vet J Mehmet Akif Ersoy U. 2016b; 1(1), 65-76.
Karabulut H, Gulay MS. Influence of bisphenol A on spermatalogical parameters of New Zealand White rabbits. Med Weter. 2020;76(6): 326-330.
Karabulut H. Erkek yeni zelanda tavşanlarında subakutbisfenol A toksisitesi. PhD thesis, Afyon Kocatepe University Health Science Institute, Afyonkarahisar, 2019.
Korkmaz A, Ahbab MA, Kolankaya D, Barlas N. Influence of vitamin C on bisphenol A, nonylphenol and octylphenol induced oxidative damages in liver of male rats. Food and Chem Toxicol. 2010; 48(10): 2865-2871.
Lin CC, Hsu YF, Lin TC, Hsu HY. Antioxidant and hepatoprotective effects of punicalagin and punicalin on acetaminophen-induced liver damage in rats. Phytotherapy Res. 2001; 15(3): 206-212.
Lin CC, Hsu YF, Lin TC.Effects of punicalagin and punicalin on carrageenan-induced inflammation in rats. J Chin Med. 1999;27(3-4): 371-376.
Liu J, Yu P, Qian W, Li Y, Zhao J, Huan F, Wang J, Xiao H.Perinatal bisphenol A exposure and adult glucose homeostasis: İdentifying critical windows of exposure. PLoSOne.2013; 8(5): e64143.
Macczak A, Bukowska B, Michalowicz J. Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes. Comp Biochem and Physiol Part C: Toxicol &Pharmacol. 2015; 176-177: 62-70.
Marmugi A, Lasserre F, Beuzelin D, Ducheix S, Huc L, Polizzi A, Chetivaux M, Pineau T, Martin PG, Guillou H, Mselli-Lakhal L.Adverse effects of long-term exposure to bisphenol A during adulthood leading to hyperglycaemia and hypercholesterolemia in mice. Toxicology.2014; 325: 133-143.
Manna P, Sinha M, Sil PC. Aqueous extract of terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders. BMC Complement Altern Med. 2006; 6(1):33-43.
Miyawaki J, Sakayama K, Kato H, Yamamoto H, Masuno H. Perinatal and postnatal exposure to bisphenol A increases adipose tissue mass and serum cholesterol level in mice. J Atheroscler Thromb. 2007;14(5): 245-252.
Moghaddam HS, Samarghandian S, Farkhondeh T.Effect of bisphenol A on blood glucose, lipid profile and oxidative stress indices in adult male mice. Toxicol Mechanisms and Methods. 2015; 25(7): 507-513.
Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: Mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun. 2005; 338 (1): 668-676.
Ogo FM, Siervo GEML, Goncalves GD, Cecchini R, Guarnier FA, Anselmo-Franci JA, Fernandes GSA. Low doses of bisphenol A can impair postnatal testicular development directly, without affecting hormonal or oxidative stress levels. Reprod Fertil Dev. 2017; 29(11): 2245-2254.
Patel C, Dadhaniya P, Hingorani L, Soni MG. Safety assessment of pomegranate fruit extract: Acute and subchronic toxicity studies. Food Chem Toxicol. 2008; 46(8): 2728-2735.doi.org /10.1016/j.fct.2008.04.035.
Qiu W, Chen J, Li Y, Chen Z, Jiang L, Yang M, Wu M. Oxidative stress and immune disturbance after long-term exposure to bisphenol A in juvenile common carp (Cyprinus carpio). Eco Toxicol Environ Safety. 2016; 16(130): 93-102.
Raja S, Ahamed KF, Kumar V, Mukherjee K, Bandyopadhyay A, Mukherjee PK. Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats. J Ethnopharmacol. 2007; 109(1): 41-47.
Reiner Ž. Resistance and intolerance to statins. Nutr Metab Cardiovasc Dis. 2014; 24(10):1057-1066.
Rosenblat M, Volkova N, Aviram M. Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cellsformation. Atherosclerosis, 2013; 226(1): 110-117.
Rosenblat M, Aviram M. Pomegranate juice protects macrophages from triglyceride accumulation: Inhibitory effect on DGAT1 activity and on triglyceride biosynthesis. Ann Nutr Metab. 2011; 58(1):1-9.
Seidlova-Wuttke D, Jarry H, Christoffel J, Rimoldi G, Wuttke W. Effects of bisphenol-A (BPA), dibutylphtalate (DBP), benzophenone-2 (BP2), procymidone (Proc), and linurone (Lin) on fat tissue, a variety of hormones and metabolic parameters: A 3 months comparison with effects of estradiol (E2) in ovariectomized (ovx) rats. Toxicology. 2005; 213(1-2): 13-24.
Sen S, Chakraborty R, Sridhar C, Reddy YSR, De B. Free radicals, antioxidants, diseases and phytomedicines: Current status and future prospect. Int J Pharm Sci Res. 2010; 3(1): 91-100. Stasiuk M, Kijanka G, Kozubek A. Transformations of erythrocytes shape and its regulation. Postepy Biochem. 2009; 55(4): 425-433.
Suhendi A, Hanwar D, Santoso B, Wicaksono AN, Widiana L. Antioxidant activity of non polar and semipolar fractions of ethanol extract of zingiber zerumbet smith leaves by spectrophotometer and ELISA reader. J Pharm Sci Res. 2018; 10(3): 439-441.
Suthar H, Verma RJ, Patel S, Jasrai YT. Green tea potentially ameliorates bisphenol A-induced oxidative stress: an in vitro and in silico study. Biochem Res Int. 2014; 2014:259763. doi: 10.1155/2014/259763.
Sun Y, Xin T, Men X, Xu Z, Tian W. In vitro and in vivo antioxidant activities of three major polyphenolic compounds in pomegranate peel: Ellagic acid, punicalin, and punicalagin. J Integr Agric. 2017; 16(8):1808-1818.
Suzuki N, Hattori, A. Bisphenol A suppress osteoclastic and osteoblastic activities in the cultured scales of goldfish. Life Sci. 2003; 73(17):2237-2247.
Suzuki N, Kambegewa A, Hattori, A. Bisphenol A Influences the plasma calcium level and inhibits calcitonin secretion in goldfish. Zool Sci. 2003; 20(6): 745-748.
Tarantino G, Valentino R, Di Somma C, D'Esposito V, Passaretti F, Pizza G, Brancato V, Orio F, Formisano P, Colao A, Savastano C. Bisphenol A in polycystic ovary syndrome and its association with liver–spleen axis. Clin Endocrinol. 2013; 78 (3): 447-453.
Videla LA. Oxidative stress signaling underlying liver disease and hepatoprotective mechanisms. World J Hepat. 2009; 1(1): 72-78.
Vora A, Londhe V, Pandita N. Herbosomes enhance the in vivo antioxidant activity and bioavailability of punicalagins from standardized pomegranate extract. J Funct Foods. 2015; 12:540-548.
Yaidikar L, Byna B, Thakur SR. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxidative brain injury in rats. J Stroke Cerebrovas Diseases. 2014; 23(10): 2869-2878.
Yildiz-Gulay O, Gulay MS. Punicalagin is beneficial for spermatogenesis in male New Zealand White rabbits. Indian J Anim Res. 2019;53(4): 457-460.
Yildiz-Gulay O, Candan G, Gulay MS. Punicalagin ameliorates spermatological parameters in bisphenol A treated New Zealand White Rabbits. Med Weter. 2020; 76(11): 641-645.
Yonar MS, Ural MS, Silici S, Yonar ME. Malathion-induced changes in the haematological profile, the immune response, and the oxidative/antioxidant status of Cyprinus carpio carpio: Protective role of propolis. Ecotoxicol Environ Saf. 2014; 102:202-209.