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KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI

Year 2017, , 146 - 153, 16.10.2017
https://doi.org/10.18229/kocatepetip.368688

Abstract

AMAÇ: Endüstriyel alanda yoğun bir şekilde kullanılan, önemli
çevre kirleticilerden biri olan kadmiyum (Cd), günlük hayattaki
maruziyetimiz nedeniyle yaşamsal bir takım tehditlere sebep
olabilmektedir. Uzun bir yarılanma ömrüne sahip olan Cd, solunum,
üriner, kardiovasküler, gastrointestinal, sinir sistemi ve kemiklerde
direkt veya dolaylı olarak toksisiteye neden olmaktadır.
Vücutta biriken Cd’un osteoporoz, anemi, eozinofili, anozmi
ve kronik rinit gibi birçok hastalığa neden olduğu bilinmektedir.
Çalışmamızda, flavonoid içeriği oldukça yüksek, ağır metal şelatlayıcı
özelliğe sahip ve antioksidan tannik asidin (TA) Cd toksikasyonundan
korunmadaki rolünü araştırmak amaçlandı.
GEREÇ VE YÖNTEM: Bu amaçla, 28 adet 200-300 gram
ağırlığında sağlıklı 3-4 aylık Spraque-Dawley soyu erkek sıçanlar
kullanıldı. Deney hayvanlarına ön tedavi amaçlı intraperitonal
(i.p) enjeksiyon ile 5 gün boyunca TA 50mg/kg/gün olarak
uygulandıktan sonra, intragastrik (i.g) enjeksiyon tek doz 35mg/
kg CdCl2 uygulandı.
BULGULAR: CdCl2 uygulaması ile azalan hemolizat, karaciğer
ve böbrek süperoksit dismutaz (SOD) değerlerini TA’nın artırdığı
gözlendi. Benzer şekilde artan hemolizat ve karaciğer malondialdehit
(MDA) değerlerini TA’nın azalttığı belirlendi. Karaciğer,
böbrek, akciğer, testis ve dalakta CdCl2 uygulaması ile artan
birikimi azaltma yönünde, TA etkili olmazken, kalpteki birikimi
azaltma yönünde TA’nın etkili olduğu analiz edildi. CdCl2 uygulaması
ile artan demir birikimini azaltma yönünde böbrek, dalak
ve kalpte TA etkili olmazken, karaciğer, akciğer ve testiste etkili
olduğu tespit edildi.
SONUÇ: Günlük diyette kullanılan yiyecek ve içeceklerin, toksik
ajanlara maruz kalma sonucu gelişebilecek bazı hastalıkları
erken dönemde önlenmesiyle, bireylerin yaşam kalitesi yükselebilecektir.
Çalışmamızda günlük yaşantımızda tüketilen
TA içeren yiyeceklerin, çeşitli şekillerde maruz kaldığımız ağır
metallerden korunma üzerine olan etkileri gözlemlendi. Elde
edilen sonuçlara göre farklı dokularda farklı sonuçlara ulaşılabileceği
belirlenirken, genel olarak değerlendirildiğinde, Cd’un
zararlı etkilerine ya da en azından bazı dokulardaki birikimini
azaltma yönünde TA’nın etkili olabileceği sonucuna ulaşıldı.

References

  • Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: A review. Int J Environ Heal R 2014;24(4):378-399.
  • Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF. Cadmiuminduced cancers in animals and in humans. Int J Occup Environ Heal 2007;13(2):202-212.
  • Kahvecioğlu Ö, Kartal G, Güven A, Timur S. Metallerin çevresel etkileri-I. Metalurji Dergisi 2003;136:47-53.
  • Haouem S, El Hani A. Effect of cadmium on lipid peroxidation and on some antioxidants in the liver, kidneys and testes of rats given diet containing cadmium-polluted radish bulbs. J Toxicol Pathol 2013;26(4):359-364.
  • Anetor JI. Rising environmental cadmium levels in developing countries: threat to genome stability and health. Niger J Physiol Sci 2012;27(2):103-115.
  • Lee YK, Park EY, Kim S. Evaluation of cadmium-ınduced nephrotoxicity using urinary metabolomic profiles in Sprague- Dawley male rats. J Toxicol Environ Heal A 2014;77(22-24):1384- 1398.
  • Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12(10):1161-1208.
  • Zarros A, Skandali N, Al-Humadi H, Liapi C. Cadmium (Cd) as a carcinogenetic factor and its participation in the induction of lung cancer. Pneumon 2008;21:172-177.
  • International Agency for Research on Cancer (IARC). Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. 1993;58:444.
  • Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez- Ruiz MC. Liver and cadmium toxicity. J Drug Metab Toxicol 2012;5:1-7.
  • Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y. Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. Int J Med Sci 2013;10(11):1485-1496.
  • Mladenovic J, Branka Ognjanovic B, Dordevic N, et al. Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats. Arh Hig Rada Toksikol 2014;65(1):37-46.
  • Giaginis C, Gatzidou E, Theocharis S. DNA repair systems as targets of cadmium toxicity. Toxicol Appl Pharmacol 2006;213(3):282-290.
  • Brama M, Politi L, Santini P, Migliaccio S, Scandurra R. Cadmium-induced apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated protein kinases pathways. J Endocrinol Invest 2012;35(2):198-208.
  • Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001;1(6):529-539.
  • Waisberga M, Josephb P, Halea B, Beyersmannc D. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 2003;192(2):95-117.
  • Hatano T, Miyatake H, Natsume M, et al. Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects. Phytochemistry 2002;59(7):749-758.
  • Yilmaz Y, Toledo RT. Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid. J Agr Food Chem 2004;52(2):255-260.
  • Pollard SE, Kuhnle GG, Vauzour D, et al. The reaction of flavonoid metabolites with peroxynitrite. Biochem Bioph Res Co 2006;350(4):960-968.
  • Labieniec M, Gabryelak T. Oxidatively modified proteins and DNA in digestive gland cells of the fresh-water mussel Unio tumidus in the presence of tannic acid and its derivatives. Mutat Res-Gen Tox En 2006;603(1):48-55.
  • Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999;12(4):564-582.
  • Labieniec M, Gabryelak T. Effects of tannins on Chinese hamster cell line B14. Mutat Res-Gen Tox En 2003;539(1):127- 135.
  • Taffetani S, Ueno Y, Meng F, et al. Tannic acid inhibits cholangiocyte proliferation after bile duct ligation via a cyclic adenosine 5’, 3’-monophosphate-dependent pathway. Am J Pathol 2005;166(6):1671-1679.
  • Marienfeld C, Tadlock L, Yamagiwa Y, Patel T. Inhibition of cholangiocarcinoma growth by tannic acid. Hepatology 2003;37(5):1097-1104.
  • Scott MD, Van Den Berg JJ, Repka T, et al. Effect of excess alpha-hemoglobin chains on cellular and membrane oxidation in model beta-thalassemic erythrocytes. J Clin Invest 1993;91(4):1706.
  • Buha A, Bulat Z, Dukic-Cosic D, Matovic V. Effects of oral and intraperitoneal magnesium treatment against cadmiuminduced oxidative stress in plasma of rats. Arh Hig Rada Toksikol 2012;63(3):247-254.
  • Ashour TH, El-Shemi AG. Caffeic acid phenyl ester prevents cadmium intoxication induced disturbances in erythrocyte indices and blood coagulability, hepatorenal dysfunction and oxidative stress in rats. Acta Haematologica Polon 2014;45(3):272-278.
  • El-Boshya ME, Rishab FE, Abdelhamidb FM, Mubarakc MS, Haddad TB. Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. J Trace Elem Med Bio 2015;29:104-110.
  • Pandey S, Parvez S, Sayeed I, Haque R, Bin-Hafeez B, Raisuddin S. Biomarkers of oxidative stress: a comparative study of river Yamuna fish Wallago attu (Bl. & Schn.). Sci Total Environ 2003;309(1):105-115.
  • Kelner MJ, Bagnell RD, Uglik SF, Montoya MA, Mullenbach GT. Heterologous expression of selenium-dependent glutathione peroxidase affords cellular resistance to paraquat. Arch Biochem Biophys 1995;323(1):40-46.
  • Bay Karabulut A, Özerol E, Temel İ, Gözükara EM, Akyol Ö. Yaş ve sigara içiminin eritrosit katalaz aktivitesi ve bazı hematolojik parametreler üzerine etkisi. Turgut Özal Tıp Merkezi Dergisi 2002;9(2):85-88.
  • Winiarska-Mieczan A. Protective effect of tannic acid on the brain of adult rats exposed to cadmium and lead. Environ Toxicol Phar 2013;36(1):9-18.
  • Zalups RK, Ahmad S. Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharm 2003;186(3):163- 188.
  • Winiarska-Mieczan A, Krusiński R, Kwiecień M. Tannic acid influence on lead and cadmium accumulation in the hearts and lungs of rats. Adv Clin Exp Med 2012;22(5):615-620.
  • Nordberg M, Nordberg GF. Toxicological aspects of metallothionein. Cell Mol Biol Res 2000;46(2):451-463.
  • Mishra S, Ghosh D, Dutta M, Chattopadhyay A, Bandyopadhyay D. Tannic acid protects against cadmiuminduced renal damages of male albino rats. Int J Pharm Sci Rev Res 2015;32(2):273-281.
  • Karamac, M. Chelation of Cu (II), Zn (II), and Fe (II) by tannin constituents of selected edible nuts. Int J Mol Sci 2009;10(12):5485-5497.
  • Afsana K, Shiga K, Ishizuka S, Hara H. Reducing effect of ingesting tannic acid on the absorption of iron, but not of zinc, copper and manganese by rats. Biosci Biotech Bioch 2004;68(3):584-592.

THE INVESTIGATION OF TANNIC ACID EFFECTS ON REMOVAL OF HEAVY METALS AND SOME BIOCHEMICAL VALUES IN THE RAT TOXICITY INDUCED BY CADMIUM

Year 2017, , 146 - 153, 16.10.2017
https://doi.org/10.18229/kocatepetip.368688

Abstract

OBJECTIVE: Cadmium (Cd), one of the major environmental
pollutants used intensively in the industrial field and could causes
a variety of vital threats due to our exposure in our daily
lives. Having a long half-life, Cd causes direct or indirect toxicity
to respiratory, urinary, cardiovascular, gastrointestinal, nervous
system and bones. It is known that Cd that accumulates in the
body causes many diseases such as osteoporosis, anemia, eosinophilia,
anosmia and chronic rhinitis. In our study, we aimed
to investigate the role of tannic acid (TA), an antioxidant substance
with a high content of flavonoids and heavy metal chelating
agents, in order to investigate its role in protecting from
Cd toxicity.

MATERIALS AND METHODS: In this study, it was used 28
Spraque-Dawley, 200-300 gr, 3-4 monthly male rats. For pre-treatment,
TA (50 mg/kg/day) was administered by intraperitoneal
(i.p) injection to the experimental groups for 5 days. And then
a single dose CdCl2 (35 mg/kg) was was administered by intragastric
(i.g).

RESULTS: It was observed that superoxide dismutase (SOD)
values decreased in hemolysate, liver and kidney by CdCl2 administration;
but increased with TA. Malondialdehyde (MDA)
values increased with CdCl2 administration whereas decreased
with TA the hemolysate and liver. TA was found to be effective
in decreasing heart accumulation, while TA was not effective
in reducing accumulation with CdCl2 administration in liver,
kidney, lung, testis and spleen. TA is not effective in reducing
increased iron accumulation with CdCl2 administration in the
kidney, spleen and heart, but in liver, lung and testis it could
be effective.

CONCLUSIONS: Food and drinks used in the daily diet may
increase the quality of life of individuals by early prevention of
certain diseases that may result in exposure to toxic agents. In
our study, it has been shown that TA, which is consumed in our
daily lives, may be effective in protecting substances from heavy
metal toxicity. According to the results obtained, different
results could be reached in different tissues; but when assessed
in general, the harmful effects of Cd, or at least the result that
TA have been achieved to reduce the accumulation of some tissues.

References

  • Rani A, Kumar A, Lal A, Pant M. Cellular mechanisms of cadmium-induced toxicity: A review. Int J Environ Heal R 2014;24(4):378-399.
  • Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF. Cadmiuminduced cancers in animals and in humans. Int J Occup Environ Heal 2007;13(2):202-212.
  • Kahvecioğlu Ö, Kartal G, Güven A, Timur S. Metallerin çevresel etkileri-I. Metalurji Dergisi 2003;136:47-53.
  • Haouem S, El Hani A. Effect of cadmium on lipid peroxidation and on some antioxidants in the liver, kidneys and testes of rats given diet containing cadmium-polluted radish bulbs. J Toxicol Pathol 2013;26(4):359-364.
  • Anetor JI. Rising environmental cadmium levels in developing countries: threat to genome stability and health. Niger J Physiol Sci 2012;27(2):103-115.
  • Lee YK, Park EY, Kim S. Evaluation of cadmium-ınduced nephrotoxicity using urinary metabolomic profiles in Sprague- Dawley male rats. J Toxicol Environ Heal A 2014;77(22-24):1384- 1398.
  • Valko M, Morris H, Cronin MT. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12(10):1161-1208.
  • Zarros A, Skandali N, Al-Humadi H, Liapi C. Cadmium (Cd) as a carcinogenetic factor and its participation in the induction of lung cancer. Pneumon 2008;21:172-177.
  • International Agency for Research on Cancer (IARC). Beryllium, cadmium, mercury, and exposures in the glass manufacturing industry. 1993;58:444.
  • Arroyo VS, Flores KM, Ortiz LB, Gómez-Quiroz LE, Gutiérrez- Ruiz MC. Liver and cadmium toxicity. J Drug Metab Toxicol 2012;5:1-7.
  • Zhou Z, Wang C, Liu H, Huang Q, Wang M, Lei Y. Cadmium induced cell apoptosis, DNA damage, decreased DNA repair capacity, and genomic instability during malignant transformation of human bronchial epithelial cells. Int J Med Sci 2013;10(11):1485-1496.
  • Mladenovic J, Branka Ognjanovic B, Dordevic N, et al. Protective effects of oestradiol against cadmium-induced changes in blood parameters and oxidative damage in rats. Arh Hig Rada Toksikol 2014;65(1):37-46.
  • Giaginis C, Gatzidou E, Theocharis S. DNA repair systems as targets of cadmium toxicity. Toxicol Appl Pharmacol 2006;213(3):282-290.
  • Brama M, Politi L, Santini P, Migliaccio S, Scandurra R. Cadmium-induced apoptosis and necrosis in human osteoblasts: role of caspases and mitogen-activated protein kinases pathways. J Endocrinol Invest 2012;35(2):198-208.
  • Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001;1(6):529-539.
  • Waisberga M, Josephb P, Halea B, Beyersmannc D. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 2003;192(2):95-117.
  • Hatano T, Miyatake H, Natsume M, et al. Proanthocyanidin glycosides and related polyphenols from cacao liquor and their antioxidant effects. Phytochemistry 2002;59(7):749-758.
  • Yilmaz Y, Toledo RT. Major flavonoids in grape seeds and skins: antioxidant capacity of catechin, epicatechin, and gallic acid. J Agr Food Chem 2004;52(2):255-260.
  • Pollard SE, Kuhnle GG, Vauzour D, et al. The reaction of flavonoid metabolites with peroxynitrite. Biochem Bioph Res Co 2006;350(4):960-968.
  • Labieniec M, Gabryelak T. Oxidatively modified proteins and DNA in digestive gland cells of the fresh-water mussel Unio tumidus in the presence of tannic acid and its derivatives. Mutat Res-Gen Tox En 2006;603(1):48-55.
  • Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999;12(4):564-582.
  • Labieniec M, Gabryelak T. Effects of tannins on Chinese hamster cell line B14. Mutat Res-Gen Tox En 2003;539(1):127- 135.
  • Taffetani S, Ueno Y, Meng F, et al. Tannic acid inhibits cholangiocyte proliferation after bile duct ligation via a cyclic adenosine 5’, 3’-monophosphate-dependent pathway. Am J Pathol 2005;166(6):1671-1679.
  • Marienfeld C, Tadlock L, Yamagiwa Y, Patel T. Inhibition of cholangiocarcinoma growth by tannic acid. Hepatology 2003;37(5):1097-1104.
  • Scott MD, Van Den Berg JJ, Repka T, et al. Effect of excess alpha-hemoglobin chains on cellular and membrane oxidation in model beta-thalassemic erythrocytes. J Clin Invest 1993;91(4):1706.
  • Buha A, Bulat Z, Dukic-Cosic D, Matovic V. Effects of oral and intraperitoneal magnesium treatment against cadmiuminduced oxidative stress in plasma of rats. Arh Hig Rada Toksikol 2012;63(3):247-254.
  • Ashour TH, El-Shemi AG. Caffeic acid phenyl ester prevents cadmium intoxication induced disturbances in erythrocyte indices and blood coagulability, hepatorenal dysfunction and oxidative stress in rats. Acta Haematologica Polon 2014;45(3):272-278.
  • El-Boshya ME, Rishab FE, Abdelhamidb FM, Mubarakc MS, Haddad TB. Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats. J Trace Elem Med Bio 2015;29:104-110.
  • Pandey S, Parvez S, Sayeed I, Haque R, Bin-Hafeez B, Raisuddin S. Biomarkers of oxidative stress: a comparative study of river Yamuna fish Wallago attu (Bl. & Schn.). Sci Total Environ 2003;309(1):105-115.
  • Kelner MJ, Bagnell RD, Uglik SF, Montoya MA, Mullenbach GT. Heterologous expression of selenium-dependent glutathione peroxidase affords cellular resistance to paraquat. Arch Biochem Biophys 1995;323(1):40-46.
  • Bay Karabulut A, Özerol E, Temel İ, Gözükara EM, Akyol Ö. Yaş ve sigara içiminin eritrosit katalaz aktivitesi ve bazı hematolojik parametreler üzerine etkisi. Turgut Özal Tıp Merkezi Dergisi 2002;9(2):85-88.
  • Winiarska-Mieczan A. Protective effect of tannic acid on the brain of adult rats exposed to cadmium and lead. Environ Toxicol Phar 2013;36(1):9-18.
  • Zalups RK, Ahmad S. Molecular handling of cadmium in transporting epithelia. Toxicol Appl Pharm 2003;186(3):163- 188.
  • Winiarska-Mieczan A, Krusiński R, Kwiecień M. Tannic acid influence on lead and cadmium accumulation in the hearts and lungs of rats. Adv Clin Exp Med 2012;22(5):615-620.
  • Nordberg M, Nordberg GF. Toxicological aspects of metallothionein. Cell Mol Biol Res 2000;46(2):451-463.
  • Mishra S, Ghosh D, Dutta M, Chattopadhyay A, Bandyopadhyay D. Tannic acid protects against cadmiuminduced renal damages of male albino rats. Int J Pharm Sci Rev Res 2015;32(2):273-281.
  • Karamac, M. Chelation of Cu (II), Zn (II), and Fe (II) by tannin constituents of selected edible nuts. Int J Mol Sci 2009;10(12):5485-5497.
  • Afsana K, Shiga K, Ishizuka S, Hara H. Reducing effect of ingesting tannic acid on the absorption of iron, but not of zinc, copper and manganese by rats. Biosci Biotech Bioch 2004;68(3):584-592.
There are 38 citations in total.

Details

Subjects Health Care Administration
Journal Section Articles
Authors

Didem Turgut Coşan

Aylin Dal This is me

Ahu Soyocak This is me

Ertuğrul Çolak This is me

Arzu Çiçek This is me

Hülyam Kurt This is me

Publication Date October 16, 2017
Acceptance Date July 24, 2017
Published in Issue Year 2017

Cite

APA Coşan, D. T., Dal, A., Soyocak, A., Çolak, E., et al. (2017). KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI. Kocatepe Tıp Dergisi, 18(4), 146-153. https://doi.org/10.18229/kocatepetip.368688
AMA Coşan DT, Dal A, Soyocak A, Çolak E, Çiçek A, Kurt H. KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI. KTD. October 2017;18(4):146-153. doi:10.18229/kocatepetip.368688
Chicago Coşan, Didem Turgut, Aylin Dal, Ahu Soyocak, Ertuğrul Çolak, Arzu Çiçek, and Hülyam Kurt. “KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI”. Kocatepe Tıp Dergisi 18, no. 4 (October 2017): 146-53. https://doi.org/10.18229/kocatepetip.368688.
EndNote Coşan DT, Dal A, Soyocak A, Çolak E, Çiçek A, Kurt H (October 1, 2017) KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI. Kocatepe Tıp Dergisi 18 4 146–153.
IEEE D. T. Coşan, A. Dal, A. Soyocak, E. Çolak, A. Çiçek, and H. Kurt, “KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI”, KTD, vol. 18, no. 4, pp. 146–153, 2017, doi: 10.18229/kocatepetip.368688.
ISNAD Coşan, Didem Turgut et al. “KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI”. Kocatepe Tıp Dergisi 18/4 (October 2017), 146-153. https://doi.org/10.18229/kocatepetip.368688.
JAMA Coşan DT, Dal A, Soyocak A, Çolak E, Çiçek A, Kurt H. KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI. KTD. 2017;18:146–153.
MLA Coşan, Didem Turgut et al. “KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI”. Kocatepe Tıp Dergisi, vol. 18, no. 4, 2017, pp. 146-53, doi:10.18229/kocatepetip.368688.
Vancouver Coşan DT, Dal A, Soyocak A, Çolak E, Çiçek A, Kurt H. KADMİYUM TOKSİSİTESİ OLUŞTURULAN SIÇANLARDA TANNİK ASİTİN, AĞIR METAL GİDERİMİ VE BAZI BİYOKİMYASAL DEĞERLER ÜZERİNE ETKİSİNİN ARAŞTIRILMASI. KTD. 2017;18(4):146-53.

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