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Effects of Boron Administration on Hematological Parameters in Rats Given Gentamicin

Year 2018, Volume: 11 Issue: 2, 140 - 147, 09.04.2018
https://doi.org/10.30607/kvj.394370

Abstract

The purpse of this study is to determine the
effects of boron (B) utilisation on hematological parameters in order to
protect from gentamicin side effects.Totally 56 Wistar
Albinomale rats were randomly divided into eight groups containing 7
animal per group. While first group served as a control(fed
a diet without boron), experimental groups
were as follows; gentamicin group (100 mg/kg, i.p.), B-5 group (5 mg/kg B, i.p.),
B-10 group (10 mg/kg B, i.p.), B-20 group (20 mg/kg B, i.p.), B-5 + gentamicin
group (5 mg/kg B and 100 mg/kg gentamicin, i.p.), B-10 + gentamicin group (10
mg/kg B and 100 mg/kg gentamicin, i.p.), and B-20 + gentamicin group (20 mg/kg
B and 100 mg/kg gentamicin, i.p.). In experimental period lasted totally 14
days,B application started to be given 4 days before injection of gentamicinto
rats and was completed the fourteenth dayof the experiment. Gentamicin started
to be given to rats on the fourth day and finished on the twelfth dayof the
experiment. In the end of the experiment, the blood samples were taken from the
animals by cardiac punctureunder anaesthesia.
In the blood smaples, erythrocyte, leukocyte and platelet counts, haematocrite
value, hemoglobin concentration, mean cell volume (MCV), mean cell hemoglobin
(MCH), mean cell hemoglobine concentration (MCHC) were determined. Gentamicin
decreased leucocyte counts and haematocrite value. High boron utilization (20
mg/kg B, i.p.) decreased significantly leucocyte counts. In conclusion, the
boron supplementation has no a preventive effect on leucocyte counts reduced by
gentamicin. 

References

  • Abdel-Naim A.B., Abdel-WahabM.H., Attia F.F. 1999. Protective effects of vitamin E and probucol against gentamicin-induced nephrotoxicity in rat. Pharmacol. Res; 40:183–187.
  • Ali B.H., Bashir A.K. 1996. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. Gen. Pharmacol; 27:349–353.
  • Altenburg J, de Graaf C, van der Werf T, Boersma W. 2011. Immunomodulatory effects of macrolide antibiotics. part 1: biological mechanisms. Respiration.81;67–74.Anandan, R, Subramanian, P. 2012. Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats, Redox Report,17; 219-226.
  • Atessahin, A., Karahan I., Yilmaz, S., Çeribaşi A.O., Princci I., 2003. The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats. Pharmac. Res., 48, 637-642.
  • Basoglu, A., Baspinar, N., Ozturk, A.S., Akalin, P.P. 2010. Effects of boron administration on hepatic steatosis, hematological and biochemical profiles in obese rats. Trace Elem.Electrol., 27; 225-231.
  • Becerra, M.C., Eraso, A.J., Albesa, I., 2003. Comparison of oxidative stress induced byciprofloxacin and pyoverdin in bacteria and in leukocytes to evaluate toxicity.Lumin 18, 334–340.
  • Bourgeois, A.C., Scott, M.E., Sabally, K., Koski, K.G. 2007. Low dietary boron reduces parasite (nematoda) survival and alters cytokine profiles but the infection modifies liver minerals in mice. J. Nutr., 137, 2080-86.
  • Bustos, P.S., Deza-Ponzio, R., Páez, P.L., Albesa, I., Cabrera, J., Virgolini, M.B., Ortega, M.G. 2016. Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobialactivity. Environ.Tox. Pharm., 48; 253-264.
  • Cakir, S., Eren, M., Senturk, M., Sarica, Z.S. 2017. The effect of boron on some biochemical parameters in experimental diabetic rats. Biol. Trace Elem.Res., https://doi.org/10.1007/s12011-017-1182-0
  • Conzelman, G.M. 1980. Pathogenesis of Renal Failure due to Aminoglicosides and Contrast Media Used in Roentgenography. Am. J. Med., 69: 767-774.
  • Correa-salde, V., Albesa, I., 2009. Reactive oxidant species and oxidation of protein and heamoglobin as biomarkers of susceptibility to stress caused by chloramphenicol. Biomed. Pharmacother. 63, 100–104.
  • Corrigan, J.J., Bell, B.M. 1971. Comparison between the polymyxins and gentamicin in preventing endotoxin-ınduced intravascular coagulation and leukopenia. Infect. Immunit., 5; 563-566.
  • Devirian TA, Volpe SL. 2003.The physiological effects of dietary boron. Critical Reviews in Food Science and Nutrition, 43(2):219–231.
  • Ertekin, A.,Karaca, M., Akkan, H.A., Cemek, M., Ormancı, N. 2003. Köpeklerde gentamisin nefrotoksikozisinde lipit peroksidasyonu, antioksidan maddeler, antioksidan vitaminler ve bazı hematolojik-biyokimyasal parametre düzeylerinin araştırılması. Tr. J. Vet. Anim. Sci., 27:535-540.
  • Farfan-Garcia, E.D., Castillo-Mendieta, N.T., Ciprés-Flores, F.J., Padilla-Martínez, I.I., Trujillo-Ferrara, J.G., Soriano-Ursúa, M.A. 2016.Current data regarding the structure-toxicity relationship of boron-containing compounds. Toxicol. Letters, 258; 115-125.
  • Hoffman DJ, Sanderson CJ, Le Captain LJ, Cromatie E, Pendleton GW. 1991. Interactive effects of boron, selenium, and dietary protein on survial, growth, and physiology in mallard ducklings.Arch. Environ. Contam. Toxicol., 20; 288-294.
  • İnce, S., Kucukkurt, I., Cigerci, I.H., Fidan, A.F., Eryavuz, A. 2010. The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J. Trace Elem. Med.Biol., 24, 161-164.
  • İnce, S., Kucukkurt, I., Demirel, H.H., Acaroz, D.A., Akbel, E., Cigerci, I.H. 2014. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108,197-204.
  • Jiang X, Li W, Zang H, Wang J, Guan C, Yang N. Apoptosis and its molecular mechanism in vestibular hair cell after gentamycin toxicity. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2005;19:886–889.
  • Kaya M, Çenesiz M 2010. Deney hayvanlarının fizyolojisi. In: Aksoy, A, Kolba-kır F, Hökelek M., editors. Laboratuvar hayvanları. Ondokuz Mayıs Üniversitesi Yayınları;p.42.
  • Kays SE, Crowell WA, Johnson MA. 1991. Iron supplementation increase gentamisin nephrotoxicity in rats. J Nutr 121: 1869-1875.
  • Kuru, R., Yarat, A. 2017. Bor ve sağlığımıza olan etkilerine güncel bir bakiş. Clin. Exp. Health Sci., 7,(3); 107-114.
  • Küçükkurt, İ., Arslan-Acaröz, D., Demirel, H.H., İnce, S., Eryavuz, A. 2017. Ratlarda gentamisin ile indüklenmiş oksidatif streste borun muhtemel koruyucu etkisinin dokularda araştırılması. Kocatepe Vet. J., 10; 172-179.
  • Lesnikovsk, Z.J. 2016. Recent developments with boron as a platform for novel drug design. Exp.Opin.Drug Discov., 11; 569-578.
  • Lewis SM. 1990.Standardization and harmonization of the blood count: the role of International Committee for Standardization in Haematology (ICSH). Eur J Haematol Suppl. 53:9-13.
  • Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. 2011. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int, 79: 33–45.
  • NseAbasi NE, Mary EW, Uduak A, Edem EAO.2014. Haematological parameters and factors affecting their values. Agric Sci, 2; 37-47.
  • Ozbek E, Turkoz Y, Sahna E, Ozugurlu F, Mizrak B, Ozbek M. 2000. Melatonin administration prevents the nephrotoxicity induced by gentamicin. BJU Int., 85;742–746.
  • Páez, P.L., Becerra, M.C., Albesa, I., 2008. Chloramphenicol-induced oxidative stress in human neutrophils. Basic Clin. Pharmacol. Toxicol. 103, 349–353.
  • Pahl, V.M., Culver, D.B., Vaziri, D.N. 2005. Boron and the kidney. J.Ren.Nutr., 15;362-370.
  • Pedraza-Chaverri J, Maldonado PD, Medina-Campos ON, Olivares-Corichi IM, Granados-Silvestre MA, Hernandez- Pando R. 2000. Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes. Free Radic. Biol. Med., 29;602–611.
  • Saha, S., Ramanthan, R., Basu, R.A., Banerjee, D., Chakrabarti, A. 2011. Elevated levels of redox regulators, membrane-bound globin chains and cytoskeletal protein fragments in hereditary spherocytosis erythrocyte proteome. Eur. J. Haematol., 87; 259-266.
  • Sayed-Ahmed MM, Nagi MN. 2007. Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol Physiol., 34;399–405.
  • Sisk DB, Colvin BM, Merrill A, Bondadi K, Bowen JM. 1990. Experimental acute inorganic boron toxicosis in the goat: Effects on serum chemistry and CSF biogenic amines. Vet.Hum.Toxicol., 32; 205-211.
  • Sweetman, S.C. (Ed.), 2009. Martindale the Complete Drug Reference.Pharmaceutical Press, London.
  • Vani, R., Reddy, C.S., Asha Devi, S. 2010. Oxidative stress in erythrocytes: A study on the effect of antioxidant mixtures during intermittent exposures to high altitude. Int.J. Biometeorol., 54; 553-562.
  • Yildirim, S., Celikezen, F.C., Oto, G., Sengul, E., Bulduk, M., Tasdemir, M., Cinar, D.A. 2017. An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol.Trace Elem.Res., DOI 10.1007/s12011-017-1089-9.

Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri

Year 2018, Volume: 11 Issue: 2, 140 - 147, 09.04.2018
https://doi.org/10.30607/kvj.394370

Abstract

Çalışma, gentamisinin
yan etkilerinden korunmak için bor (B) kullanımının hematolojik parametrelere
etkilerini belirlemek amacıyla yapıldı. Toplamda 56 adet Wistar Albino erkek sıçan her grupta 7 hayvan olacak
şekilde 8 gruba rastgele ayrıldı. İlk grup kontrol grubu olarak ayrılırken
(borsuz yemle beslendiler), deneme grupları ise, gentamisin (100 mg/kg i.p.),
B-5 (5 mg/kg B, i.p.), B-10 (10 mg/kg B, i.p.), B-20 (20 mg/kg B, i.p.), B-5 +
gentamisin (5 mg/kg B ve 100 mg/kg gentamisin, i.p.), B-10 + gentamisin (10 mg/kg
B ve 100 mg/kg gentamisin, i.p.), B-20 + gentamisin (20 mg/kg B ve 100 mg/kg
gentamisin, i.p.) şeklinde oluşturuldu. Toplam 14 gün süren deneme döneminde,
sıçanlara gentamisin enjeksiyonundan 4 gün önce B verilmeye başlandı ve
denemenin 14.gününde tamamlandı.Gentamisin uygulamasına 4. gün başlandı ve
deneme döneminin 12. gününde bu uygulama sonlandırıldı. Denemenin sonunda,
hayvanlardan kan örnekleri anestezi altında kalpten alındı. Alınan kan
örneklerinde; eritrosit, lökosit ve trombosit sayıları ile hematokrit değer,
hemoglobin miktarı, ortalama eritrosit hacmi (MCV), ortalama eritrosit
hemoglobini (MCH) ve ortalama eritrosit hemoglobin düzeyi (MCHC) belirlendi.
Gentamisin lökosit sayısını ve hematokrit değeri düşürdü. Yüksek B uygulaması
(20 mgB/kg) lökosit sayısını önemli düzeyde azalttı. Sonuç olarak, bor
uygulamasının gentamisinin yol açtığı lökosit sayısındaki azalmayı önlemede
etkiye sahip olmadığı kanaatine varıldı.

References

  • Abdel-Naim A.B., Abdel-WahabM.H., Attia F.F. 1999. Protective effects of vitamin E and probucol against gentamicin-induced nephrotoxicity in rat. Pharmacol. Res; 40:183–187.
  • Ali B.H., Bashir A.K. 1996. Effect of superoxide dismutase treatment on gentamicin nephrotoxicity in rats. Gen. Pharmacol; 27:349–353.
  • Altenburg J, de Graaf C, van der Werf T, Boersma W. 2011. Immunomodulatory effects of macrolide antibiotics. part 1: biological mechanisms. Respiration.81;67–74.Anandan, R, Subramanian, P. 2012. Renal protective effect of hesperidin on gentamicin-induced acute nephrotoxicity in male Wistar albino rats, Redox Report,17; 219-226.
  • Atessahin, A., Karahan I., Yilmaz, S., Çeribaşi A.O., Princci I., 2003. The effect of manganese chloride on gentamicin-induced nephrotoxicity in rats. Pharmac. Res., 48, 637-642.
  • Basoglu, A., Baspinar, N., Ozturk, A.S., Akalin, P.P. 2010. Effects of boron administration on hepatic steatosis, hematological and biochemical profiles in obese rats. Trace Elem.Electrol., 27; 225-231.
  • Becerra, M.C., Eraso, A.J., Albesa, I., 2003. Comparison of oxidative stress induced byciprofloxacin and pyoverdin in bacteria and in leukocytes to evaluate toxicity.Lumin 18, 334–340.
  • Bourgeois, A.C., Scott, M.E., Sabally, K., Koski, K.G. 2007. Low dietary boron reduces parasite (nematoda) survival and alters cytokine profiles but the infection modifies liver minerals in mice. J. Nutr., 137, 2080-86.
  • Bustos, P.S., Deza-Ponzio, R., Páez, P.L., Albesa, I., Cabrera, J., Virgolini, M.B., Ortega, M.G. 2016. Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobialactivity. Environ.Tox. Pharm., 48; 253-264.
  • Cakir, S., Eren, M., Senturk, M., Sarica, Z.S. 2017. The effect of boron on some biochemical parameters in experimental diabetic rats. Biol. Trace Elem.Res., https://doi.org/10.1007/s12011-017-1182-0
  • Conzelman, G.M. 1980. Pathogenesis of Renal Failure due to Aminoglicosides and Contrast Media Used in Roentgenography. Am. J. Med., 69: 767-774.
  • Correa-salde, V., Albesa, I., 2009. Reactive oxidant species and oxidation of protein and heamoglobin as biomarkers of susceptibility to stress caused by chloramphenicol. Biomed. Pharmacother. 63, 100–104.
  • Corrigan, J.J., Bell, B.M. 1971. Comparison between the polymyxins and gentamicin in preventing endotoxin-ınduced intravascular coagulation and leukopenia. Infect. Immunit., 5; 563-566.
  • Devirian TA, Volpe SL. 2003.The physiological effects of dietary boron. Critical Reviews in Food Science and Nutrition, 43(2):219–231.
  • Ertekin, A.,Karaca, M., Akkan, H.A., Cemek, M., Ormancı, N. 2003. Köpeklerde gentamisin nefrotoksikozisinde lipit peroksidasyonu, antioksidan maddeler, antioksidan vitaminler ve bazı hematolojik-biyokimyasal parametre düzeylerinin araştırılması. Tr. J. Vet. Anim. Sci., 27:535-540.
  • Farfan-Garcia, E.D., Castillo-Mendieta, N.T., Ciprés-Flores, F.J., Padilla-Martínez, I.I., Trujillo-Ferrara, J.G., Soriano-Ursúa, M.A. 2016.Current data regarding the structure-toxicity relationship of boron-containing compounds. Toxicol. Letters, 258; 115-125.
  • Hoffman DJ, Sanderson CJ, Le Captain LJ, Cromatie E, Pendleton GW. 1991. Interactive effects of boron, selenium, and dietary protein on survial, growth, and physiology in mallard ducklings.Arch. Environ. Contam. Toxicol., 20; 288-294.
  • İnce, S., Kucukkurt, I., Cigerci, I.H., Fidan, A.F., Eryavuz, A. 2010. The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. J. Trace Elem. Med.Biol., 24, 161-164.
  • İnce, S., Kucukkurt, I., Demirel, H.H., Acaroz, D.A., Akbel, E., Cigerci, I.H. 2014. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108,197-204.
  • Jiang X, Li W, Zang H, Wang J, Guan C, Yang N. Apoptosis and its molecular mechanism in vestibular hair cell after gentamycin toxicity. Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2005;19:886–889.
  • Kaya M, Çenesiz M 2010. Deney hayvanlarının fizyolojisi. In: Aksoy, A, Kolba-kır F, Hökelek M., editors. Laboratuvar hayvanları. Ondokuz Mayıs Üniversitesi Yayınları;p.42.
  • Kays SE, Crowell WA, Johnson MA. 1991. Iron supplementation increase gentamisin nephrotoxicity in rats. J Nutr 121: 1869-1875.
  • Kuru, R., Yarat, A. 2017. Bor ve sağlığımıza olan etkilerine güncel bir bakiş. Clin. Exp. Health Sci., 7,(3); 107-114.
  • Küçükkurt, İ., Arslan-Acaröz, D., Demirel, H.H., İnce, S., Eryavuz, A. 2017. Ratlarda gentamisin ile indüklenmiş oksidatif streste borun muhtemel koruyucu etkisinin dokularda araştırılması. Kocatepe Vet. J., 10; 172-179.
  • Lesnikovsk, Z.J. 2016. Recent developments with boron as a platform for novel drug design. Exp.Opin.Drug Discov., 11; 569-578.
  • Lewis SM. 1990.Standardization and harmonization of the blood count: the role of International Committee for Standardization in Haematology (ICSH). Eur J Haematol Suppl. 53:9-13.
  • Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. 2011. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int, 79: 33–45.
  • NseAbasi NE, Mary EW, Uduak A, Edem EAO.2014. Haematological parameters and factors affecting their values. Agric Sci, 2; 37-47.
  • Ozbek E, Turkoz Y, Sahna E, Ozugurlu F, Mizrak B, Ozbek M. 2000. Melatonin administration prevents the nephrotoxicity induced by gentamicin. BJU Int., 85;742–746.
  • Páez, P.L., Becerra, M.C., Albesa, I., 2008. Chloramphenicol-induced oxidative stress in human neutrophils. Basic Clin. Pharmacol. Toxicol. 103, 349–353.
  • Pahl, V.M., Culver, D.B., Vaziri, D.N. 2005. Boron and the kidney. J.Ren.Nutr., 15;362-370.
  • Pedraza-Chaverri J, Maldonado PD, Medina-Campos ON, Olivares-Corichi IM, Granados-Silvestre MA, Hernandez- Pando R. 2000. Garlic ameliorates gentamicin nephrotoxicity: relation to antioxidant enzymes. Free Radic. Biol. Med., 29;602–611.
  • Saha, S., Ramanthan, R., Basu, R.A., Banerjee, D., Chakrabarti, A. 2011. Elevated levels of redox regulators, membrane-bound globin chains and cytoskeletal protein fragments in hereditary spherocytosis erythrocyte proteome. Eur. J. Haematol., 87; 259-266.
  • Sayed-Ahmed MM, Nagi MN. 2007. Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol Physiol., 34;399–405.
  • Sisk DB, Colvin BM, Merrill A, Bondadi K, Bowen JM. 1990. Experimental acute inorganic boron toxicosis in the goat: Effects on serum chemistry and CSF biogenic amines. Vet.Hum.Toxicol., 32; 205-211.
  • Sweetman, S.C. (Ed.), 2009. Martindale the Complete Drug Reference.Pharmaceutical Press, London.
  • Vani, R., Reddy, C.S., Asha Devi, S. 2010. Oxidative stress in erythrocytes: A study on the effect of antioxidant mixtures during intermittent exposures to high altitude. Int.J. Biometeorol., 54; 553-562.
  • Yildirim, S., Celikezen, F.C., Oto, G., Sengul, E., Bulduk, M., Tasdemir, M., Cinar, D.A. 2017. An investigation of protective effects of litium borate on blood and histopathological parameters in acute cadmium-induced rats. Biol.Trace Elem.Res., DOI 10.1007/s12011-017-1089-9.
There are 37 citations in total.

Details

Primary Language Turkish
Journal Section RESEARCH ARTICLE
Authors

İbrahim Durmuş

Sinan İnce

Mehmet Naci Salim This is me

Abdullah Eryavuz

İsmail Küçükkurt

Publication Date April 9, 2018
Acceptance Date March 16, 2018
Published in Issue Year 2018 Volume: 11 Issue: 2

Cite

APA Durmuş, İ., İnce, S., Salim, M. N., Eryavuz, A., et al. (2018). Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri. Kocatepe Veterinary Journal, 11(2), 140-147. https://doi.org/10.30607/kvj.394370
AMA Durmuş İ, İnce S, Salim MN, Eryavuz A, Küçükkurt İ. Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri. kvj. June 2018;11(2):140-147. doi:10.30607/kvj.394370
Chicago Durmuş, İbrahim, Sinan İnce, Mehmet Naci Salim, Abdullah Eryavuz, and İsmail Küçükkurt. “Gentamisin Verilen sıçanlara Bor uygulamasının Hematolojik Parametre düzeylerine Etkileri”. Kocatepe Veterinary Journal 11, no. 2 (June 2018): 140-47. https://doi.org/10.30607/kvj.394370.
EndNote Durmuş İ, İnce S, Salim MN, Eryavuz A, Küçükkurt İ (June 1, 2018) Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri. Kocatepe Veterinary Journal 11 2 140–147.
IEEE İ. Durmuş, S. İnce, M. N. Salim, A. Eryavuz, and İ. Küçükkurt, “Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri”, kvj, vol. 11, no. 2, pp. 140–147, 2018, doi: 10.30607/kvj.394370.
ISNAD Durmuş, İbrahim et al. “Gentamisin Verilen sıçanlara Bor uygulamasının Hematolojik Parametre düzeylerine Etkileri”. Kocatepe Veterinary Journal 11/2 (June 2018), 140-147. https://doi.org/10.30607/kvj.394370.
JAMA Durmuş İ, İnce S, Salim MN, Eryavuz A, Küçükkurt İ. Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri. kvj. 2018;11:140–147.
MLA Durmuş, İbrahim et al. “Gentamisin Verilen sıçanlara Bor uygulamasının Hematolojik Parametre düzeylerine Etkileri”. Kocatepe Veterinary Journal, vol. 11, no. 2, 2018, pp. 140-7, doi:10.30607/kvj.394370.
Vancouver Durmuş İ, İnce S, Salim MN, Eryavuz A, Küçükkurt İ. Gentamisin verilen sıçanlara bor uygulamasının hematolojik parametre düzeylerine etkileri. kvj. 2018;11(2):140-7.

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