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Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri

Year 2018, Volume: 13 Issue: 2, 182 - 190, 25.10.2018

Gözde Yaman Bülbül Leyla Mis , Emin Şengül , Serkan Yıldırım , Fikret Çelebi , Ali Çınar

https://doi.org/10.17094/ataunivbd.360839
Cited By: 5

Abstract

Bu çalışmada Cyclophosphamide (CYP) uygulaması yapılan ratlarda karaciğer enzimleri (Aspartat aminotransferaz (AST), Alanin aminotransferaz (ALT), Alkalen fosfataz (ALP) ve histopatolojisi üzerine Naringin’in protektif etkilerinin araştırılması amaçlanmaktadır. Araştırmamızda yaklaşık 200-250 g ağırlığında, 40 adet erkek erişkin Sprague Dawley ırkı rat kullanıldı ve 5 grup oluşturuldu. Karaciğer enzimlerinin analizleri otoanalizörde ve spektrofotometrede yapıldı. Hematoksilen eosin ile boyanan karaciğer doku örnekleri ışık mikroskobunda incelendi. CYP’nin ratlarda hepatotoksiteye yol açtığı ve karaciğer enzimlerini artırdığı görüldü. AST, ALT ve ALP değerleri Kontrol grubunda 58±11, 32±8, 38±6; CYP grubunda 237±42, 168±44, 74±11; Naringin 50+CYP grubunda 223±33, 158±42, 62±9; Naringin 100+CYP grubunda 117±25, 107±24, 48±8; Naringin 100 grubunda ise 54±9, 31±7, 36±6 sırasıyla olarak bulundu. Kontrol grubundan elde edilen değerlere göre CYP verilen gruplarda ki AST, ALT ve ALP değerlerinin tamamında P<0.001 düzeyinde artış söz konusudur. CYP’nin karaciğer dokusunda oluşturduğu dejeneratif ve nekrotik doku hasarının Naringin’in etkisiyle dozlara bağlı olarak azaldığı saptandı. Sonuç olarak, Naringin’in farklı dozlarının, CYP ile indüklenen hepatotoksisitede protektif etkili olduğu belirlendi.

Keywords

Cyclophosphamide Histopatoloji Karaciğer Enzimleri Naringin Rat

References

  • 1. Ernest E., Cassiletth B., 1998. The prevealence of complementary. Alternative medicine in cancer. Cancer, 83, 777-782.
  • 2. Akay H., Akay T., Seçilmiş S., Koçak Z., Donderici O., 2006. Hepatotoxcity after low-dose cyclophosphamide. South Med J, 99, 1399-1400.
  • 3. DeSouza L., Shen Y., Bognar AL., 2000. Disruption of cytoplasmic and mitochondrial folylpolyglutamate synthetase activity in Saccharomyces cerevisiae. Arch Biochem Biophys, 376, 299-312.
  • 4. Meirow D., Assad G., Dor J., Rabinovici J., 2004. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod, 19, 1294-1299.
  • 5. Thatcher RW., Walker RA., Gerson I., Geisler FH., 1989, EEG discriminant analyses of mild head trauma. EEG Clin Neurophysiol, 73, 94-106.
  • 6. Muratori L., Ferrari R., Muratori P., Granito A., Bianchi FB., 2005. Acute icteric hepatitis induced by a short course of low-dose cyclophosphamide in a patient with lupus nephritis. Dig Dis Sci, 50, 2364-2365.
  • 7. Webb H., Jaureguiberry G., Dufek S., Tullus K., Bockenhauer D., 2016. Cyclophosphamide and rituximab in frequently relapsing/steroid-dependent nephrotic syndrome. Pediatr Nephrol, 31, 589-594.
  • 8. Doğan Z., Kocahan S., Erdemli E., Köse E., Yılmaz I., Ekincioğlu Z., Ekinci N., Turkoz Y., 2015. Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin. Cytotechnology, 67, 1031-1038.
  • 9. Nafees S., Rashid S., Ali N., Hasan SK., Sultana S., 2015. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem Biol Interact, 231, 98-107.
  • 10. Bacanlı M., Başaran AA., Başaran N., 2015. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin. Food Chem Toxicol, 81, 160-170.
  • 11. Galati EM., Monforte MT., d’Aquino A., Miceli N., Di Mauro D., Sanogo R., 1998. Effects of naringin on experimental ulcer in rats. Phytomedicine, 5, 361-366.
  • 12. Xie Y., Yang W., Tang F., Chen X., Ren L., 2015. Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr Med Chem, 22, 132-149.
  • 13. Liu, L., Zuo, Z., Lu, S., Liu, A., & Liu, X. (2017). Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro. IJBMS, 20(7), 813..
  • 14. Ueng YF., Chang YL., Oda Y., Park SS., Liao JF., Lin MF., Chen CF., 1999. In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver. Life Sci, 65, 2591-2602.
  • 15. Stanton ME., Legendre AM., 1986. Effects of cyclophosphamide in dogs and cats. JAWMA, 188, 1319-1322.
  • 16. Korkmaz A., Topal T., Oter S., 2007. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARPactivation. Cell Biol Toxicol, 23, 303-312.
  • 17. Delarmelina JM., Dutra JC., Batitucci Mdo C., 2014. Antimutagenic activity of ipriflavone against the DNA-damage induced by cyclophosphamide in mice. Food Chem Toxicol, 65, 140-146.
  • 18. Anderson D., Bishop JB., Garner RC., Ostrosky-Wegman P., Selby PB., 1995. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res, 330, 115-181.
  • 19. Yeh ET., Tong AT., Lenihan DJ., Yusuf SW., Swafford J., Champion C., Ewer MS., 2004. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 109, 3122-3131.
  • 20. Skinner R., Sharkey IM, Pearson AD, Craft AW., 1993. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol, 11, 173-190.
  • 21. Patra K, Bose S., Sarkar S., Rakshit J., Jana S., Mukherjee A., Roy A., Mandal DP., Bhattacharjee S., 2012. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid. Chem Biol Interact, 195, 231-239.
  • 22. Çelebi F., Gelen V., Çınar A., Şengül E., 2014. The effect of rutin on overactive contractility of bladder smooth muscle in the model of cyclophosphamide-induced cystitis in rats. The FASEB Journal, 28, 690-15.
  • 23. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Çelebi F., Çınar A., 2017. The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
  • 24. Gelen V., Şengül E., Gedikli S., Çelebi F., Çınar A., Kara A., Özkanlar S., Gür C., 2016. The Effects of Quercetin on Cyclophosphamide-Induced Cardiotoxicity in Rats. Acta Physiol, 218, 14-15.
  • 25. Agrawal S., Gupta D., 2013. Assessment of liver damage in male albino rats after repetitive heat stress of moderate level. Natl J Physiol Pharm Pharmacol, 3, 147-152.
  • 26. Agrawal S., Gupta D., 2013. Behavioural changes in albino rats due to repetitive heat stress of moderate level. Int J Med Sci Public Health, 2, 650-653.
  • 27. Agrawal S., Gupta D., 2014. A study of regenerative ability of liver after repetitive heat stress induced liver injury, Int J Med Sci Public Health, 3, 19-23.
  • 28. Gencer G., Çınar A., Comba B., 2015. Stresin ratlarda bazı karaciğer enzimleri AST, ALT, ALP üzerine etkilerinin araştırılması. Atatürk Üniv Vet Bil Derg, 10, 21-26.
  • 29. Aşcıoğlu YT., 2005. Sıçanlardaki kronik alkolik karaciğer hasarına likopenin etkisi. Uzmanlık Tezi, Sağlık Bakanlığı Şişli Etfal Eğitim ve Araştırma Hastanesi Biyokimya Bölümü, İstanbul, Türkiye.
  • 30. Samir P., Desai MD., Isa-Pratt S., 2004. Clinician's guide to laboratory medicine. Lexi-Comp Inc, 66, 612-613.
  • 31. Nishimura M., Teschke R., 1982. Effect of chronic alcohol concumption on the activites of liver plasma membrane enzymes. Biochem Pharmacol, 31, 377-381.
  • 32. Teschke R., Neuefeind M., Nishimura M., Strohmeyer G., 1983. Hepatic gammagltamyltransferase activity in alcoholic fatty liver: comparison with other liver enzymes in man and rats. Gut, 24, 625-630.
  • 33. Glinsukon T., Taycharpipranai S., Toskulkao C., 1997. Alphatoxin 1 hepatotoxicity in rats preated with ethanol. Experientia, 34, 869-870.
  • 34. Ishii H., Watanabe Y., Okuno F., Takagi T., Munakata Y., Miura S., Shigeta Y., Tsuchiya M., 1998. Alcohol- induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics, Alcohol Clin Exp Res, 12, 111-115.
  • 35. Zaidi SMKR., Al-Qirim TM., Banu N., 2005. Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs R D, 6, 157-165.
  • 36. Öztabak K., Mengi A., 2004. Lektin Verilen Normal ve Tümörlü Farelerde Serum, Karaciğer ve Böbrek AST, ALT, GGT, ALP, CK Aktiviteleri Uludag Univ J Fac Vet Med, 23, 93-97.
  • 37. Sakr SA., Shalaby SY., Beder RH., 2017. Ameliorative Effect of Fennel Oil on Cyclophosphamide Induced Hepatotoxicity in Albino Rats. Br J Pharm Res, 17, 1-12.
  • 38. King PD., Perry MC., 2001. Hepatotoxicity of chemotherapy. Oncologist, 6, 162-176.
  • 39. Aubrey DA., 1970. Massive hepatic necrosis after cyclophosphamide. Br Med J, 3, 588.
  • 40. Walters D., Robinson RG., Dick-Smith JB., Corrigon AB., Webb J., 1972. Poor response in two cases of juvenile rheumatoid arthritis to treatment with cyclophosphamide. Med J Aust, 2, 1070.
  • 41. Bacon AM., Rosenberg SA., 1982. Cyclophosphamide hepatotoxicity in a patient with systemic lupus erythematosus. Ann Intern Med, 97, 62-63.
  • 42. Goldberg JW., Lidsky MD., 1985. Cyclophosphamide associated hepatotoxicity. South Med J, 78, 222-223.
  • 43. Oyagbemi AA., Omobowale OT., Asenuga ER., Akinleye AS., Ogunsanwo RO., Saba AB., 2016. Cyclophosphamide-induced Hepatotoxicity in Wistar Rats: The Modulatory Role of Gallic Acid as a Hepatoprotective and Chemopreventive Phytochemical. Int J Prev Med, 7, 51-64.
  • 44. Pari L., Amudha K., 2011. Hepatoprotective role of naringin on nickel-induced toxicity in male Wistar rats. Eur J Pharmacol, 650, 364-370.

Protective Effects of Naringin on Liver Enzymes (AST, ALT, ALP) and Histopathology in Cyclophosphamide-Induced Rats

Year 2018, Volume: 13 Issue: 2, 182 - 190, 25.10.2018

Gözde Yaman Bülbül Leyla Mis , Emin Şengül , Serkan Yıldırım , Fikret Çelebi , Ali Çınar

https://doi.org/10.17094/ataunivbd.360839
Cited By: 5

Abstract

In this study, it is aimed to investigate the protective effects of Naringin on liver enzymes (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and histopathology in CYP-induced rats. In our study, forty male adult Sprague Dawley rat weighing approximately 200-250 g were used and 5 gropus formed. Analyzes of liver enzymes were done in auto analyzer and spectrophotometer. The liver tissue samples stained with hematoxylin eosin were examined by light microscopy. CYP was found to cause hapatotoxicity and showed increased liver enzymes in rats. AST, ALT and ALP values were 58±11, 32±8, 38±6 in the control group; 237±42, 168±44, 74±11 in the CYP group; 223±33, 158±42, 62±9 in the Naringin 50+CYP group; 117±25, 107±24, 48±8 in Naringin 100+CYP group; 54±9, 31±7, 36±6 in the group of Naringin 100 were found respectively. According to the values obtained from the control group, there is an increase of P<0.001 in all of the AST, ALT and ALP values in CYP-treated groups. Degenerative and necrotic tissue damage caused by CYP in the liver tissue was found to be reduced as dose-dependent with effect of Naringin. In conclusion, different doses of Naringin were determined to be protective effective for CYP-induced hepatotoxicity.

Keywords

Cyclophosphamide Histopathology Liver Enzeymes Naringin Rat

References

  • 1. Ernest E., Cassiletth B., 1998. The prevealence of complementary. Alternative medicine in cancer. Cancer, 83, 777-782.
  • 2. Akay H., Akay T., Seçilmiş S., Koçak Z., Donderici O., 2006. Hepatotoxcity after low-dose cyclophosphamide. South Med J, 99, 1399-1400.
  • 3. DeSouza L., Shen Y., Bognar AL., 2000. Disruption of cytoplasmic and mitochondrial folylpolyglutamate synthetase activity in Saccharomyces cerevisiae. Arch Biochem Biophys, 376, 299-312.
  • 4. Meirow D., Assad G., Dor J., Rabinovici J., 2004. The GnRH antagonist cetrorelix reduces cyclophosphamide-induced ovarian follicular destruction in mice. Hum Reprod, 19, 1294-1299.
  • 5. Thatcher RW., Walker RA., Gerson I., Geisler FH., 1989, EEG discriminant analyses of mild head trauma. EEG Clin Neurophysiol, 73, 94-106.
  • 6. Muratori L., Ferrari R., Muratori P., Granito A., Bianchi FB., 2005. Acute icteric hepatitis induced by a short course of low-dose cyclophosphamide in a patient with lupus nephritis. Dig Dis Sci, 50, 2364-2365.
  • 7. Webb H., Jaureguiberry G., Dufek S., Tullus K., Bockenhauer D., 2016. Cyclophosphamide and rituximab in frequently relapsing/steroid-dependent nephrotic syndrome. Pediatr Nephrol, 31, 589-594.
  • 8. Doğan Z., Kocahan S., Erdemli E., Köse E., Yılmaz I., Ekincioğlu Z., Ekinci N., Turkoz Y., 2015. Effect of chemotherapy exposure prior to pregnancy on fetal brain tissue and the potential protective role of quercetin. Cytotechnology, 67, 1031-1038.
  • 9. Nafees S., Rashid S., Ali N., Hasan SK., Sultana S., 2015. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: role of NFκB/MAPK pathway. Chem Biol Interact, 231, 98-107.
  • 10. Bacanlı M., Başaran AA., Başaran N., 2015. The antioxidant and antigenotoxic properties of citrus phenolics limonene and naringin. Food Chem Toxicol, 81, 160-170.
  • 11. Galati EM., Monforte MT., d’Aquino A., Miceli N., Di Mauro D., Sanogo R., 1998. Effects of naringin on experimental ulcer in rats. Phytomedicine, 5, 361-366.
  • 12. Xie Y., Yang W., Tang F., Chen X., Ren L., 2015. Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr Med Chem, 22, 132-149.
  • 13. Liu, L., Zuo, Z., Lu, S., Liu, A., & Liu, X. (2017). Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro. IJBMS, 20(7), 813..
  • 14. Ueng YF., Chang YL., Oda Y., Park SS., Liao JF., Lin MF., Chen CF., 1999. In vitro and in vivo effects of naringin on cytochrome P450-dependent monooxygenase in mouse liver. Life Sci, 65, 2591-2602.
  • 15. Stanton ME., Legendre AM., 1986. Effects of cyclophosphamide in dogs and cats. JAWMA, 188, 1319-1322.
  • 16. Korkmaz A., Topal T., Oter S., 2007. Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic cystitis; implication of reactive oxygen and nitrogen species as well as PARPactivation. Cell Biol Toxicol, 23, 303-312.
  • 17. Delarmelina JM., Dutra JC., Batitucci Mdo C., 2014. Antimutagenic activity of ipriflavone against the DNA-damage induced by cyclophosphamide in mice. Food Chem Toxicol, 65, 140-146.
  • 18. Anderson D., Bishop JB., Garner RC., Ostrosky-Wegman P., Selby PB., 1995. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res, 330, 115-181.
  • 19. Yeh ET., Tong AT., Lenihan DJ., Yusuf SW., Swafford J., Champion C., Ewer MS., 2004. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 109, 3122-3131.
  • 20. Skinner R., Sharkey IM, Pearson AD, Craft AW., 1993. Ifosfamide, mesna, and nephrotoxicity in children. J Clin Oncol, 11, 173-190.
  • 21. Patra K, Bose S., Sarkar S., Rakshit J., Jana S., Mukherjee A., Roy A., Mandal DP., Bhattacharjee S., 2012. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid. Chem Biol Interact, 195, 231-239.
  • 22. Çelebi F., Gelen V., Çınar A., Şengül E., 2014. The effect of rutin on overactive contractility of bladder smooth muscle in the model of cyclophosphamide-induced cystitis in rats. The FASEB Journal, 28, 690-15.
  • 23. Şengül E., Gelen V., Gedikli S., Özkanlar S., Gür C., Çelebi F., Çınar A., 2017. The protective effect of quercetin on cyclophosphamide-Induced lung toxicity in rats. Biomed Pharmacother, 92, 303-307.
  • 24. Gelen V., Şengül E., Gedikli S., Çelebi F., Çınar A., Kara A., Özkanlar S., Gür C., 2016. The Effects of Quercetin on Cyclophosphamide-Induced Cardiotoxicity in Rats. Acta Physiol, 218, 14-15.
  • 25. Agrawal S., Gupta D., 2013. Assessment of liver damage in male albino rats after repetitive heat stress of moderate level. Natl J Physiol Pharm Pharmacol, 3, 147-152.
  • 26. Agrawal S., Gupta D., 2013. Behavioural changes in albino rats due to repetitive heat stress of moderate level. Int J Med Sci Public Health, 2, 650-653.
  • 27. Agrawal S., Gupta D., 2014. A study of regenerative ability of liver after repetitive heat stress induced liver injury, Int J Med Sci Public Health, 3, 19-23.
  • 28. Gencer G., Çınar A., Comba B., 2015. Stresin ratlarda bazı karaciğer enzimleri AST, ALT, ALP üzerine etkilerinin araştırılması. Atatürk Üniv Vet Bil Derg, 10, 21-26.
  • 29. Aşcıoğlu YT., 2005. Sıçanlardaki kronik alkolik karaciğer hasarına likopenin etkisi. Uzmanlık Tezi, Sağlık Bakanlığı Şişli Etfal Eğitim ve Araştırma Hastanesi Biyokimya Bölümü, İstanbul, Türkiye.
  • 30. Samir P., Desai MD., Isa-Pratt S., 2004. Clinician's guide to laboratory medicine. Lexi-Comp Inc, 66, 612-613.
  • 31. Nishimura M., Teschke R., 1982. Effect of chronic alcohol concumption on the activites of liver plasma membrane enzymes. Biochem Pharmacol, 31, 377-381.
  • 32. Teschke R., Neuefeind M., Nishimura M., Strohmeyer G., 1983. Hepatic gammagltamyltransferase activity in alcoholic fatty liver: comparison with other liver enzymes in man and rats. Gut, 24, 625-630.
  • 33. Glinsukon T., Taycharpipranai S., Toskulkao C., 1997. Alphatoxin 1 hepatotoxicity in rats preated with ethanol. Experientia, 34, 869-870.
  • 34. Ishii H., Watanabe Y., Okuno F., Takagi T., Munakata Y., Miura S., Shigeta Y., Tsuchiya M., 1998. Alcohol- induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics, Alcohol Clin Exp Res, 12, 111-115.
  • 35. Zaidi SMKR., Al-Qirim TM., Banu N., 2005. Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs R D, 6, 157-165.
  • 36. Öztabak K., Mengi A., 2004. Lektin Verilen Normal ve Tümörlü Farelerde Serum, Karaciğer ve Böbrek AST, ALT, GGT, ALP, CK Aktiviteleri Uludag Univ J Fac Vet Med, 23, 93-97.
  • 37. Sakr SA., Shalaby SY., Beder RH., 2017. Ameliorative Effect of Fennel Oil on Cyclophosphamide Induced Hepatotoxicity in Albino Rats. Br J Pharm Res, 17, 1-12.
  • 38. King PD., Perry MC., 2001. Hepatotoxicity of chemotherapy. Oncologist, 6, 162-176.
  • 39. Aubrey DA., 1970. Massive hepatic necrosis after cyclophosphamide. Br Med J, 3, 588.
  • 40. Walters D., Robinson RG., Dick-Smith JB., Corrigon AB., Webb J., 1972. Poor response in two cases of juvenile rheumatoid arthritis to treatment with cyclophosphamide. Med J Aust, 2, 1070.
  • 41. Bacon AM., Rosenberg SA., 1982. Cyclophosphamide hepatotoxicity in a patient with systemic lupus erythematosus. Ann Intern Med, 97, 62-63.
  • 42. Goldberg JW., Lidsky MD., 1985. Cyclophosphamide associated hepatotoxicity. South Med J, 78, 222-223.
  • 43. Oyagbemi AA., Omobowale OT., Asenuga ER., Akinleye AS., Ogunsanwo RO., Saba AB., 2016. Cyclophosphamide-induced Hepatotoxicity in Wistar Rats: The Modulatory Role of Gallic Acid as a Hepatoprotective and Chemopreventive Phytochemical. Int J Prev Med, 7, 51-64.
  • 44. Pari L., Amudha K., 2011. Hepatoprotective role of naringin on nickel-induced toxicity in male Wistar rats. Eur J Pharmacol, 650, 364-370.
There are 44 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Araştırma Makaleleri
Authors

Gözde Yaman Bülbül This is me

Leyla Mis

Emin Şengül

Serkan Yıldırım

Fikret Çelebi

Ali Çınar

Publication Date October 25, 2018
Published in Issue Year 2018 Volume: 13 Issue: 2

Cite

APA Yaman Bülbül, G., Mis, L., Şengül, E., Yıldırım, S., et al. (2018). Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 13(2), 182-190. https://doi.org/10.17094/ataunivbd.360839
AMA Yaman Bülbül G, Mis L, Şengül E, Yıldırım S, Çelebi F, Çınar A. Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. October 2018;13(2):182-190. doi:10.17094/ataunivbd.360839
Chicago Yaman Bülbül, Gözde, Leyla Mis, Emin Şengül, Serkan Yıldırım, Fikret Çelebi, and Ali Çınar. “Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) Ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 13, no. 2 (October 2018): 182-90. https://doi.org/10.17094/ataunivbd.360839.
EndNote Yaman Bülbül G, Mis L, Şengül E, Yıldırım S, Çelebi F, Çınar A (October 1, 2018) Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 13 2 182–190.
IEEE G. Yaman Bülbül, L. Mis, E. Şengül, S. Yıldırım, F. Çelebi, and A. Çınar, “Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri”, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 13, no. 2, pp. 182–190, 2018, doi: 10.17094/ataunivbd.360839.
ISNAD Yaman Bülbül, Gözde et al. “Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) Ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 13/2 (October 2018), 182-190. https://doi.org/10.17094/ataunivbd.360839.
JAMA Yaman Bülbül G, Mis L, Şengül E, Yıldırım S, Çelebi F, Çınar A. Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2018;13:182–190.
MLA Yaman Bülbül, Gözde et al. “Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) Ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 13, no. 2, 2018, pp. 182-90, doi:10.17094/ataunivbd.360839.
Vancouver Yaman Bülbül G, Mis L, Şengül E, Yıldırım S, Çelebi F, Çınar A. Cyclophosphamide İle İndüklenmiş Ratlarda Karaciğer Enzimleri (AST, ALT, ALP) ve Histopatolojisi Üzerine Naringin’in Protektif Etkileri. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2018;13(2):182-90.

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Atatürk Üniversitesi Veteriner Bilimleri Dergisi
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https://doi.org/10.17094/ataunivbd.700017