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Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi

Year 2020, Volume: 17 Issue: 2, 156 - 163, 27.07.2020
https://doi.org/10.32707/ercivet.774340

Abstract

Bu çalışmada, karbon tetraklorür (CCl4) ile akut karaciğer hasarı oluşturulan ratlarda nar çekirdeği yağının (NÇY) karaciğer dokusunda oluşabilecek lezyonlar üzerine koruyucu etkisi, hücresel apoptozda kaspaz aktivasyonları, serum Alanin Amino Transferaz (ALT) aktivitesi, trigliserit, total protein, albümin, total kolesterol düzeyleri ve karaciğer malondialdehit (MDA) düzeyi değerlendirildi. Çalışmada 32 adet rat, her grupta 8 adet olmak üzere 4 gruba ayrıldı. İlk grup kontrol olarak belirlendi. İkinci gruba 4 hafta her gün 2 ml/kg/canlı-ağırlık dozunda NÇY gavaj ile verildi. Üçüncü gruba 1:1 oranında mısır yağı ile dilüe edilen 1.0 ml/kg/canlı-ağırlık iki doz CCl4 ilk hafta 3 gün ara ile intraperitoneal olarak enjekte edildi. Dördüncü gruba 2 ml/kg/canlı-ağırlık dozunda NÇY 4 hafta her gün, gavaj ile verilirken ilk hafta 3 gün ara ile 2 doz intraperitoneal 1 ml/kg/canlı-ağırlık, dilüe edilmiş CCl4 uygulandı. Kontrol gruplarında normal karaciğer doku yapısı gözlenirken; CCl4 grubunda hepatositlerinde yoğun makro ve mikroveziküler yağlanma, portal bölgede ve parankimde çoğunluğu lenfositlerden oluşan mononüklear hücre infiltrasyon alanları ile nekrotik değişiklikler görüldü. NÇY uygulamalarında histopatolojik değişiklikler CCl4 grubuna göre kısmen azalırken, kaspaz 3 ve 9 aktivitesi de sınırlı sayıda azaldı. CCl4 ile artış gösteren ALT aktivitesi NÇY uygulaması ile önemli düzeyde düşüş (P<0.05), serum total protein değerlerinde artış (P<0.001) gözlendi. CCl4 uygulanması karaciğer MDA düzeyini önemli düzeyde artırırken (P<0.001), NÇY’nın uygulamaları istatistiki önemde etkilemedi. Sonuç olarak; CCl4 ile birlikte NÇY verilen deney gruplarında karaciğer hasarına karşı histopatolojik değişiklikler üzerinde olumlu etkisi gözlenmemesine karşın, bazı biyokimyasal değerleri kontrol grubu değerlerine yaklaştırdığından, kısmen iyileştirici bir etkisinin olabileceği, ancak bu iyileşmenin karaciğer dokusundaki hasara yansımadığı düşünülmektedir

References

  • Ali SA, Rizk MZ, Ibrahim NA, Abdallah MS, Sharara HM, Moustafa MM. Protective role of Juniperus phoenicea and Cupressus sempervirens against CCl4. World J Gastrointest Pharmacol Ther 2010; 1(6): 123-31.
  • Basu S. Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003; 189: 113-127.
  • Botsoglou NA, Taitzoglou IA, Botsoglou E, Zervos I, Kokoli A, Christaki E, Nikolaidis E. Effect of long-term dietary administration of oregano and rosemary on the antioxidant status of rat serum, liver, kidney and heart after carbon tetrachloride-induced oxidative stress. J Sci Food Agric 2009; 89: 1397-406.
  • Chan CC, Lee KC, Huang YH, Chou CK, Lin HC, Lee FY. Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. J Gastroenterol Hepatol 2014; 29(3), 603-13.
  • Domitrović R, Škoda M, Marchesi VV, Cvijanović O, Pugel EP, Štefan MB. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol 2013; 51: 370-8.
  • Gram DY, Atasever A, Eren M. Effect of pomegranate (Punica granatum) seed oil on carbon tetrachloride-induced acute and chronic hepatotoxicity in rats. J Pharmacogn Phytochem 2018; 10(2): 124-9.
  • Green Cj, Kneight J, Precious S, Simpkin S. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab Anim 1981; 15: 163-70.
  • Gurib-Fakim, A. Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Aspects Med 2006; 27(1): 1-93.
  • Ibrahim MAR, Okail HAM, Emam NMM. Ameliorative Effects of Pomegranate Peel Extract on Hepatotoxicity Induced by Carbon Tetrachloride in Mice. I J Res Stud Biosci 2016; 4(10): 23-31.
  • Kumar R, Kumar S, Patra A, Jayalakshmi S. Hepatoprotective activity of aerial parts of Plumbago zeylanica linn against carbon tetrachloride-induced hepatotoxicity in rats. Int J Pharmacy Pharmaceut Sci 2009; 1: 171-5.
  • Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109(2): 177-206.
  • Liu H, Wang Z, Nowicki MJ. Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice. World J Gastroenterol 2014; 20(48): 18189-98.
  • Luna LG. Manual of Histologic Staining Methods; of the Armed Forces Institute of Pathology, New York Blakiston Division, McGraw-Hill, 1968; 34-75.
  • Melo ILP, Silva AMO, Carvalho EBT, Yoshime LT, Mancini DAP, Mancini-Filho J. Effect of Pomegranate (Punica granatum L.) Seed Oil on Markers of Oxidative Stress Induced by Carbon Tetra-chloride in Wistar Rats. Int J Food Sci Nutr Diet 2015; 5: 1-8.
  • Moure A, Cruz JM, Franco D, Domı́nguez JM, Sineiro J, Domı́nguez H, Parajó JC. Natural antioxidants from residual sources. Food Chem 2001; 72(2): 145-171. Naczk M, Shahidi F. Extraction and analysis of phenolics in food. J Chromatogr A 2004; 1054(1): 95-111.
  • Namiki M. Antioxidants/antimutagens in food. Crit Rev Food Sci Nutr 1990; 29(4): 273-300.
  • Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: Mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005; 338: 668–76.
  • Noda Y, Kaneyuki T, Mori A, Packer L. Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J Agric Food Chem 2002; 50(1): 166-171.
  • Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. N Y Sci J 2011; 4: 27-41.
  • Parajuli DR, Park EJ, Che XH, Jiang WY, Kim YC, Sohn D, Lee S. PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo. Molecules 2013; 18(2): 2122-34.
  • Ravikumar S, Gnanadesigan M. Hepatoprotective and antioxidant activity of a mangrove plant Lumnitzera racemosa. Asian Pac J Trop Biomed 2011; 1(5): 348-52.
  • Recknagel RO, Glende EA JR, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut 1989; 43: 139-54.
  • Saha SS, Chakraborty A, Ghosh S, Ghosh M. Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity. Eur J Nutr 2012; 51: 483-95.
  • Sarıca ZS, Liman BC. Ratlarda Pentaklorofenol Zehirlenmesinde Nar Çekirdeği Yağının Lipid Peroksidasyonu ve Biyokimyasal Parametrelere Etkileri. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 2016; 13(2): 109-119.
  • Schinella G, Mosca S, Cienfuegos-Jovellanos E, et al. Antioxidant properties of polyphenol-rich cocoa products industrially processed. Food Res Int 2010; 43(6): 1614-23.
  • Shaban NZ, El-Kersh MA, Bader-Eldin MM, Kato SA, Hamoda AF. Effect of Punica granatum (pomegranate) juice extract on healthy liver and hepatotoxicity induced by diethylnitrosamine and phenobarbital in male rats. J Med Food 2014; 17: 339-49.
  • Shenoy KA, Somayaji SN, Bairy KL. Hepatoprotective effects of Ginkgo biloba against CCl4-induced hepatic injury in rats. Indian J Pharmacol 2001; 33: 260-6.
  • Sumalatha S, Padma D, Pai KSR, Kotian SR, Kumar N, Bhat KM. Hepatoprotective activity of aqueous extract of caesalpinia bonduc against CCl4 induced chronic hepatotoxicity. Int J Pharm Pharm Sci 2016; 8(4): 207-11.
  • Tao LL, Cheng YY, Ding D, Mei S, Xu JW, Yu J, Xu ZD. C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo. Apoptosis 2012; 17(5): 492-502.
  • Xie J, Liu J, Chen TM, Lan Q, Zhang QY, Liu B, Zhu RZ. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World J Gastroenterol 2015; 21(18): 5473-81.
  • Yang LN, Fu ZX, Li MZ, Hu MY, Zhu MY, Zhou GY, Lin Q. Protective effect of pomegranate seed extracts on carbon tetrachloride-induced liver injury in mice. J Jilin Univ Med Ed 2011; 5: 21.
  • Yehia HM, Al Olayan EM, Elkhadragy MF. Hepatoprotective role of the pomegranate (Punica granatum) juice on carbon tetrachloride induced oxidative stress in rats. Life Sci J 2013; 10: 1534-44.
  • Zeashan H, Amresh G, Singh S, Rao CV. Hepatoprotective activity of Amaranthus spinosus in experimental animals. Food Chem Toxicol 2008; 46(11): 3417-21.

The Effects of Pomegranate Seed Oil on Acute Liver Damage Induced Carbon Tetrachloride in Rats and Determination of Hepatic Apoptosis and Caspase Activity

Year 2020, Volume: 17 Issue: 2, 156 - 163, 27.07.2020
https://doi.org/10.32707/ercivet.774340

Abstract

In this study, the protective effect of pomegranate seed oil (PSO) on liver tissue lesions in rats induced by carbon tetrachloride (CCl4) in acute liver injury, caspase activations in cellular apoptosis, serum Alanine Amino Transferase (ALT) activity, triglyceride, total protein, albumin, total cholesterol levels, and liver malondialdehyde (MDA) levels were evaluated. Thirty-two rats were divided into four groups as 8 rats in each group. The first group was determined as control. The second group was given 2 ml/kg/body-weight PSO gavage daily for 4 weeks. In the third group, 1.0 ml/kg/ body-weight of two doses of CCl4 diluted 1:1 with corn oil was injected intraperitoneally at 3 days intervals in the first week. The fourth group received 2 ml/kg/body- weight PSO every day for 4 weeks by gavage and 2 doses intraperitoneally 1 ml/kg/body-weight, diluted CCl4 at 3 days intervals in the first week. While normal liver tissue structure was observed in the control groups; In the CCl4 group, intense macro and microvesicular steatosis of hepatocytes, mononuclear cell infiltration areas mostly composed of lymphocytes in the portal region and parenchyma and necrotic changes were observed. Histopathological changes in PSO applications were partially decreased compared to the CCl4 group, while caspase 3 and 9 activity decreased to a limited number. ALT activity increased with CCl4 and decreased with PSO application (P<0.05) and increased serum total protein values (P<0.001). While the administration of CCl4 significantly increased liver MDA levels (P<0.001), it was not significantly affected by the application of PSO. As a result; although there was no positive effect on histopathological changes against liver damage in experimental groups given PSO with CCl4 since it brings the biochemical values closer to the control group values, it is thought that it may have a partially curative effect, but this improvement does not reflect the damage in liver tissue.

References

  • Ali SA, Rizk MZ, Ibrahim NA, Abdallah MS, Sharara HM, Moustafa MM. Protective role of Juniperus phoenicea and Cupressus sempervirens against CCl4. World J Gastrointest Pharmacol Ther 2010; 1(6): 123-31.
  • Basu S. Carbon tetrachloride-induced lipid peroxidation: Eicosanoid formation and their regulation by antioxidant nutrients. Toxicology 2003; 189: 113-127.
  • Botsoglou NA, Taitzoglou IA, Botsoglou E, Zervos I, Kokoli A, Christaki E, Nikolaidis E. Effect of long-term dietary administration of oregano and rosemary on the antioxidant status of rat serum, liver, kidney and heart after carbon tetrachloride-induced oxidative stress. J Sci Food Agric 2009; 89: 1397-406.
  • Chan CC, Lee KC, Huang YH, Chou CK, Lin HC, Lee FY. Regulation by resveratrol of the cellular factors mediating liver damage and regeneration after acute toxic liver injury. J Gastroenterol Hepatol 2014; 29(3), 603-13.
  • Domitrović R, Škoda M, Marchesi VV, Cvijanović O, Pugel EP, Štefan MB. Rosmarinic acid ameliorates acute liver damage and fibrogenesis in carbon tetrachloride-intoxicated mice. Food Chem Toxicol 2013; 51: 370-8.
  • Gram DY, Atasever A, Eren M. Effect of pomegranate (Punica granatum) seed oil on carbon tetrachloride-induced acute and chronic hepatotoxicity in rats. J Pharmacogn Phytochem 2018; 10(2): 124-9.
  • Green Cj, Kneight J, Precious S, Simpkin S. Ketamine alone and combined with diazepam or xylazine in laboratory animals: a 10 year experience. Lab Anim 1981; 15: 163-70.
  • Gurib-Fakim, A. Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol Aspects Med 2006; 27(1): 1-93.
  • Ibrahim MAR, Okail HAM, Emam NMM. Ameliorative Effects of Pomegranate Peel Extract on Hepatotoxicity Induced by Carbon Tetrachloride in Mice. I J Res Stud Biosci 2016; 4(10): 23-31.
  • Kumar R, Kumar S, Patra A, Jayalakshmi S. Hepatoprotective activity of aerial parts of Plumbago zeylanica linn against carbon tetrachloride-induced hepatotoxicity in rats. Int J Pharmacy Pharmaceut Sci 2009; 1: 171-5.
  • Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 2007; 109(2): 177-206.
  • Liu H, Wang Z, Nowicki MJ. Caspase-12 mediates carbon tetrachloride-induced hepatocyte apoptosis in mice. World J Gastroenterol 2014; 20(48): 18189-98.
  • Luna LG. Manual of Histologic Staining Methods; of the Armed Forces Institute of Pathology, New York Blakiston Division, McGraw-Hill, 1968; 34-75.
  • Melo ILP, Silva AMO, Carvalho EBT, Yoshime LT, Mancini DAP, Mancini-Filho J. Effect of Pomegranate (Punica granatum L.) Seed Oil on Markers of Oxidative Stress Induced by Carbon Tetra-chloride in Wistar Rats. Int J Food Sci Nutr Diet 2015; 5: 1-8.
  • Moure A, Cruz JM, Franco D, Domı́nguez JM, Sineiro J, Domı́nguez H, Parajó JC. Natural antioxidants from residual sources. Food Chem 2001; 72(2): 145-171. Naczk M, Shahidi F. Extraction and analysis of phenolics in food. J Chromatogr A 2004; 1054(1): 95-111.
  • Namiki M. Antioxidants/antimutagens in food. Crit Rev Food Sci Nutr 1990; 29(4): 273-300.
  • Niki E, Yoshida Y, Saito Y, Noguchi N. Lipid peroxidation: Mechanisms, inhibition, and biological effects. Biochem Biophys Res Commun 2005; 338: 668–76.
  • Noda Y, Kaneyuki T, Mori A, Packer L. Antioxidant activities of pomegranate fruit extract and its anthocyanidins: delphinidin, cyanidin, and pelargonidin. J Agric Food Chem 2002; 50(1): 166-171.
  • Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on the hepatoprotective effects of pomegranate and guava ethanol extracts. N Y Sci J 2011; 4: 27-41.
  • Parajuli DR, Park EJ, Che XH, Jiang WY, Kim YC, Sohn D, Lee S. PF2401-SF, standardized fraction of Salvia miltiorrhiza, induces apoptosis of activated hepatic stellate cells in vitro and in vivo. Molecules 2013; 18(2): 2122-34.
  • Ravikumar S, Gnanadesigan M. Hepatoprotective and antioxidant activity of a mangrove plant Lumnitzera racemosa. Asian Pac J Trop Biomed 2011; 1(5): 348-52.
  • Recknagel RO, Glende EA JR, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Therapeut 1989; 43: 139-54.
  • Saha SS, Chakraborty A, Ghosh S, Ghosh M. Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity. Eur J Nutr 2012; 51: 483-95.
  • Sarıca ZS, Liman BC. Ratlarda Pentaklorofenol Zehirlenmesinde Nar Çekirdeği Yağının Lipid Peroksidasyonu ve Biyokimyasal Parametrelere Etkileri. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 2016; 13(2): 109-119.
  • Schinella G, Mosca S, Cienfuegos-Jovellanos E, et al. Antioxidant properties of polyphenol-rich cocoa products industrially processed. Food Res Int 2010; 43(6): 1614-23.
  • Shaban NZ, El-Kersh MA, Bader-Eldin MM, Kato SA, Hamoda AF. Effect of Punica granatum (pomegranate) juice extract on healthy liver and hepatotoxicity induced by diethylnitrosamine and phenobarbital in male rats. J Med Food 2014; 17: 339-49.
  • Shenoy KA, Somayaji SN, Bairy KL. Hepatoprotective effects of Ginkgo biloba against CCl4-induced hepatic injury in rats. Indian J Pharmacol 2001; 33: 260-6.
  • Sumalatha S, Padma D, Pai KSR, Kotian SR, Kumar N, Bhat KM. Hepatoprotective activity of aqueous extract of caesalpinia bonduc against CCl4 induced chronic hepatotoxicity. Int J Pharm Pharm Sci 2016; 8(4): 207-11.
  • Tao LL, Cheng YY, Ding D, Mei S, Xu JW, Yu J, Xu ZD. C/EBP-α ameliorates CCl4-induced liver fibrosis in mice through promoting apoptosis of hepatic stellate cells with little apoptotic effect on hepatocytes in vitro and in vivo. Apoptosis 2012; 17(5): 492-502.
  • Xie J, Liu J, Chen TM, Lan Q, Zhang QY, Liu B, Zhu RZ. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World J Gastroenterol 2015; 21(18): 5473-81.
  • Yang LN, Fu ZX, Li MZ, Hu MY, Zhu MY, Zhou GY, Lin Q. Protective effect of pomegranate seed extracts on carbon tetrachloride-induced liver injury in mice. J Jilin Univ Med Ed 2011; 5: 21.
  • Yehia HM, Al Olayan EM, Elkhadragy MF. Hepatoprotective role of the pomegranate (Punica granatum) juice on carbon tetrachloride induced oxidative stress in rats. Life Sci J 2013; 10: 1534-44.
  • Zeashan H, Amresh G, Singh S, Rao CV. Hepatoprotective activity of Amaranthus spinosus in experimental animals. Food Chem Toxicol 2008; 46(11): 3417-21.
There are 33 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Görkem Ekebaş This is me 0000-0001-9094-677X

Ayhan Atasever This is me

Meryem Şentürk This is me

Duygu Yaman Gram This is me

Meryem Eren This is me

Publication Date July 27, 2020
Submission Date January 7, 2020
Published in Issue Year 2020 Volume: 17 Issue: 2

Cite

APA Ekebaş, G., Atasever, A., Şentürk, M., Yaman Gram, D., et al. (2020). Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 17(2), 156-163. https://doi.org/10.32707/ercivet.774340
AMA Ekebaş G, Atasever A, Şentürk M, Yaman Gram D, Eren M. Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Erciyes Üniv Vet Fak Derg. July 2020;17(2):156-163. doi:10.32707/ercivet.774340
Chicago Ekebaş, Görkem, Ayhan Atasever, Meryem Şentürk, Duygu Yaman Gram, and Meryem Eren. “Ratlarda Karbon Tetraklorür Ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi Ve Kaspaz Aktivitesi Ile Hepatik Apoptozisin Belirlenmesi”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17, no. 2 (July 2020): 156-63. https://doi.org/10.32707/ercivet.774340.
EndNote Ekebaş G, Atasever A, Şentürk M, Yaman Gram D, Eren M (July 1, 2020) Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17 2 156–163.
IEEE G. Ekebaş, A. Atasever, M. Şentürk, D. Yaman Gram, and M. Eren, “Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi”, Erciyes Üniv Vet Fak Derg, vol. 17, no. 2, pp. 156–163, 2020, doi: 10.32707/ercivet.774340.
ISNAD Ekebaş, Görkem et al. “Ratlarda Karbon Tetraklorür Ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi Ve Kaspaz Aktivitesi Ile Hepatik Apoptozisin Belirlenmesi”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17/2 (July 2020), 156-163. https://doi.org/10.32707/ercivet.774340.
JAMA Ekebaş G, Atasever A, Şentürk M, Yaman Gram D, Eren M. Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Erciyes Üniv Vet Fak Derg. 2020;17:156–163.
MLA Ekebaş, Görkem et al. “Ratlarda Karbon Tetraklorür Ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi Ve Kaspaz Aktivitesi Ile Hepatik Apoptozisin Belirlenmesi”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, vol. 17, no. 2, 2020, pp. 156-63, doi:10.32707/ercivet.774340.
Vancouver Ekebaş G, Atasever A, Şentürk M, Yaman Gram D, Eren M. Ratlarda Karbon Tetraklorür ile Oluşturulan Akut Karaciğer Hasarı Üzerine Nar Çekirdeği Yağının Etkisi ve Kaspaz Aktivitesi ile Hepatik Apoptozisin Belirlenmesi. Erciyes Üniv Vet Fak Derg. 2020;17(2):156-63.