Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication

Hasan Akşit; Dilek Akşit; Ayşegül Bildik; Hatibe Kara; Özlem Yavuz; Kamil Seyrek

doi:10.1501/Vetfak_0000002649

Letter to Editor

Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication

Year 2015, Volume: 62 Issue: 1, 1 - 5, 01.03.2015

Hasan Akşit Dilek Akşit Ayşegül Bildik Hatibe Kara Özlem Yavuz Kamil Seyrek

https://doi.org/10.1501/Vetfak_0000002649

Cited By: 7

Abstract

In this study, the effects of intraperitoneal applications N-acetyl cysteine (NAC) an glutathione (GSH) precursor, on GSH and related enzymes, lipid peroxidation activities in the erythrocyte and liver tissue were investigated. For this purpose, effects of the NAS were investigated on playing an important role in detoxification reactions of biomolecules; GSH/GSSG, GSH reductase, GSH-px, NADP/NADPH activity, superoxide dismutase (SOD) and as an indicator of lipid peroxidation malondialdehyde (MDA) in liver toxicity formed by carbon tetrachloride (CCl4). In this study in order to create liver toxicity in rats, CCl4 was applied 3 times with an interval of one day 1 ml/kg intraperitoneal (ip) in 1/1 ratio of olive oil in the form of solution. In order to determine the protective effect of the NAS, NAS application was started 3 days before (ip 50 mg /kg/day) that CCl4 injected to tested group and continued during the experiment. 24 hours after the last injection of CCl4, blood and liver samples were taken under ether anesthesia. It was determined that AST, ALT, GSSG, NADP/NADPH and MDA levels increased importantly in CCl4 group than control group and also observed that the levels decreased with addition of NAS. Also it was observed that GSH, GSH reductase, GSH-Px and SOD levels significantly decreased in CCl4 group than control group, the levels were increased with addition of the NAS. It is concluded that NAS may be useful repairing oxidative damage in liver injury induced by CCl4 and protecting the harmful effects of reactive oxygen species with removing oxygen radicals also may support the defense of tissues against oxidative stress and direct antioxidant effect

Keywords

CCl4, N-acetyl cysteine, glutathione, lipid peroxidation, rat

References

Adewole SO, Salako AA, Doherty OW, Naicker T (2007): Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats. AJBR, 10, 153-164.
Akyol Ö (2004): Şizofrenide oksidatif stres. Kocatepe Tıp Dergisi, 5, 15-25.
Allameh A, Vansoun EY, Zarghi A (1997): Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity. Mechanisms of Ageing Development, 95, 71-79.
Altomare E, Vendemiale G, Alano O (1988): Hepatic glutathione content in patients with alcoholic and nonalcoholic liver diseases. Life Sci, 43, 991-998.
Angulo P, Lindor KD (2002): Treatment of non-alcoholic steatohepatitis. Best Pract Res Cl Ga, 5, 797-810.
Bray TM, Taylor CG (1994): Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochemical Pharmacology, 47, 2113-2123.
Candas R, Sohal S, Radyuk SN, Klickhko VI, Orr WC (1997): Molecularorganization of the glutathione reductase gene in Drosophila melanogaster. ABB, 339, 323-334.
Chávez E, Gordillo KR, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Moreno MG, Muriel P (2008): Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J Appl Toxicol, 28, 35–43.
Cnubben NHP, Rıetjens IMCM, Wortelboer H, Van Zanden J, Van Bladeren PJ (2001): The interplay of glutathione-related processes inantioxidant defense. Environmental Toxicology and Pharmacology, 10, 141- 152.
Çakır M (1997): Aspirin ve vitamin E (α-Tokoferol)’nin farelerde (Mus musculus) karaciğer total süperoksit dismutaz ve katalaz aktivitelerine etkileri. Yüksek Lisans Tezi, Ondokuz Mayıs Üniversitesi Biyoloji Anabilim Dalı, Samsun, Türkiye.
Çetinkaya A (2009): Ratlarda N-asetil sistein ve L- karnitin’in karbon tetraklorür ile oluşturulan akut karaciğer hasarı üzerine etkileri. Yan Dal Uzmanlık Tezi. Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Gastroenteroloji Bilim Dalı, Kahramanmaraş, Türkiye.
Düzgüner V (2005): Deneysel olarak diyabet olusturulan tavşanlarda çinkonun lipit peroksidasyonu ve antioksidan sistem üzerine etkisi. Yüksek Lisans Tezi, Mustafa Kemal Üniversitesi Sağlık Bilimleri Enstitüsü, Hatay, Türkiye.
Fairbanks VF, Klee GG (1999): Biochemical aspects of hemotology. In: Burtis CA, Ashwood ER (Eds.), Tietz Textbook of Clinical Chemistry, W.B. Saunders Company, Philadelphia: p. 1642–1710.
Fischer-Nielsen A, Poulsen HE, Hansen BA, Hage E, Keiding S (1991): CCl4 cirrhosis in rats: Irreversible histological changes and differantiated functional impairment. J Hepatol, 12, 110-117.
Gülcen B, Karaca Ö, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ (2012): Deneysel karbon tetraklorür zehirlen- mesinde akciğer doku hasarı ve melatonin hormonunun koruyucu rolü: Işık mikroskobik ve biyokimyasal bir çalışma. Düzce Tıp Dergisi, 14, 37-42.
Güven A, Güven A, Gülmez M (2003): The effect of kefir on the activities of GSH-Px, GST, CAT, GSH and LPO levels in carbon tetrachloride-induced mice tissues. J Vet Med B, 50, 412–416.
Güven A, Maraşlı N, Kaya N (2003): Karbon tetraklorür (CCl4) ve etil alkol’ün fare eritrosit antioksidan ve plazma lipid peroksidasyonuna etkisi. Kafkas Üniv Vet Fak Derg, 9, 1-4.
Ichi I, Kamikawaa C, Nakagawaa T, Kobayashia K, Kataokaa R, Nagata E, Kitamuraa Y, Nakazakia C, Matsurab T, Kojoa S (2009): Neutral sphingomyelinase- induced ceramide accumulation by oxidative stres during carbon tetrachloride intoxication. Toxicology, 261, 33–40.
Junqueira LC, Carneiro J, Kelley RO M (1992): Basic Histology. 7nd Ed. New Jersey: Prentice Hill International Inc.
Kang W, Yang H, Hong HJ, Han CH, Lee YJ (2012): Anti-oxidant activities of kiwi fruit extract on carbon tetrachloride-induced liver injury in mice. Korean J Vet Res, 52, 270-280.
Khan MR, Younus T (2011): Prevention of CCl4-induced oxidative damage in adrenal gland by digera muricata extract in rat. Pak J Pharm Sci, 24, 469-473.
Khand FD, Gordge MP, Robertson WG, Noronha- Dutra AA, Hothersall JS (2002): Mitochondrial superoxide production during oxalate mediated oxidative stres in renal epithelial cells. Free Radic Biol Med, 32, 1339-1350.
Kurt H, Basaran A, Aral E (2005): Sıçanlarda karbon tetraklorit’in oluşturduğu oksidatif stresin likopen ile önlenmesi. Türkiye Klinikleri J Med Sci, 25, 167-173.
Liu X, Fu YM, Meadows GG (2011): Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells. Oncology Letters, 2, 349-355.
Loguercio C, Blanco CDV, Coltorti M, Nardi G (1992): Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis. Scand J Clin Lab Invest, 52, 207-213.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951): Protein measurement with the Folin Phenol Reagent. J Biol Chem, 193, 265-275.
Lu KL, Tsai CC, Ho LK, Lin CC, Chang YS (2002): Preventive effect of the Taiwan folk medicine ixeris laevigata var. Oldhami on a-nophthyl-isothiocyarate and carbon tetrachlorideinduced acute liver injury in rats. Phytother Res, 16, 45-50.
Meister A (1991): Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Therapeut, 51, 155-194.
Memişoğulları R (2005): Diabette serbest radikallerin rolü ve antioksidanların etkisi. Düzce Tıp Fakültesi Dergisi, 3, 30-39.
Roderick P (2004): Liver function tests: defining what’s normal. Brit Med J, 328, 987.
Sun Y, Larry WO, Ying Li (1988): Simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
Tanrıverdi G (2005): Karbon tetraklorür (CCl4) ile oluşturulmuş karaciğer hasarında değişik dozlardaki nikotinamidin protektif etkisinin ışık ve elektron mikroskobik olarak incelenmesi. Yüksek Lisans Tezi, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Histoloji ve Embriyoloji Anabilim Dalı, İstanbul, Türkiye.
Thrall KD, Vucelick ME, Gies RA, Zangar RC, Weitz KK, Poet TS, Springer DL, Grant DM, Benson JM (2000): Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. J Toxicol Env Heal A, 60, 531-548.
Tietz WN (1987): Measurement of plasma hemoglobin. Fundamental of Clinical Chemistry, Saunders Company; p. 805-806.
Üstündağ B, Bahçecioğlu İH, Şahin K, Gülcü F, Düzgün S, Özercan İH, Gürsu MF (2005): Soy izoflavonların karbon tetraklorüre (CCl4) bağlı karaciğer hasarı ve plazma paraoksonaz ile arilesteraz aktivite düzeylerine olan etkileri. FÜ Sağ Bil Derg, 19, 263-271.
Wong N, Blair AR, Morahan G, Andrikopoulos S (2010): The deletion variant of nicotinamide nucleotide transhydrogenase (nnt) does not affect insulin secretion or glucose tolerance. Endocrinology, 151, 96–102.
Yılmaz S, Bahçecioğlu İH (2000): Karbontetraklorür ile siroz oluşturulmuş ratlarda lipid peroksidasyonu, antioksidant enzim ile piruvat kinaz aktiviteleri. Tr J Vet Anim Sci, 24, 25-28.
Yoshoiko T, Kawada K, Shimada T (1979): Lipid peroxidation in maternal and cord blood and protective mechanism against active oxygen toxicity in the blood. Am J Obstet Gynecol, 135, 372–376.
Yüce A, Aksakal M (2007): Ratların karaciğer ve testis dokusundaki antioksidan aktivite üzerine nar suyunun etkisi. FÜ Sağ Bil Derg, 21, 253-256.
Zafarullah M, Li WQ, Sylvester J, Ahmad M (2003): Molecular mechanisms of Nacetylcysteine actions. Cell Mol Life Sci, 60, 6-20. Geliş tarihi: 20.01.2014 / Kabul tarihi: 24.04.2014

Deneysel karaciğer intoksikasyonunda N-asetil sistein’in glutatyon metabolizması ve lipid peroksidasyonuna etkileri

Year 2015, Volume: 62 Issue: 1, 1 - 5, 01.03.2015

Hasan Akşit Dilek Akşit Ayşegül Bildik Hatibe Kara Özlem Yavuz Kamil Seyrek

https://doi.org/10.1501/Vetfak_0000002649

Cited By: 7

Abstract

Bu çalışmada eritrosit ve karaciğer dokusunda glutatyon (GSH) öncüsü N-Asetil Sisteinin (NAS) periton içi uygulamasının GSH ve ilişkili enzimler ile lipid peroksidasyona olan etkileri araştırıldı. Bu amaçla, karaciğerde karbon tetraklorür (CCl4) ile oluşturulan toksisite modelinde detoksifikasyon reaksiyonlarında önemli rol oynayan biyomoleküllerden GSH/GSSG, GSH reduktaz, GSH-px, , NADP/NADPH aktivitesi, lipit peroksidasyon göstergesi malondialdehit (MDA) ile süperoksit dismutaz (SOD) üzerine NAS’in etkisi araştırıldı. Karaciğer toksisitesi oluşturmak amacıyla ratlara CCl4, 1/1 oranında zeytinyağındaki çözeltisi periton içi yolla 1 ml/kg, gün aşırı 3 defa enjekte edildi. NAS’in koruyucu etkisinin belirlenmesi amacıyla, NAS uygulamasına (periton içi 50 mg/kg/gün) CCl4 enjeksiyonundan 3 gün önce başlandı ve deney süresince devam edildi. CCl4’ün son enjeksiyonundan 24 saat sonra eter anestezisi altında kan ve karaciğer örnekleri alındı. CCl4 verilen grupta AST, ALT, GSSG, NADP/NADPH ve MDA düzeylerinin kontrol grubuna göre anlamlı olarak arttığı ve NAS verilmesi ile düzeylerinin düştüğü belirlendi. CCl4 grubunda GSH, GSH redüktaz, GSH-px ve SOD düzeylerinin ise kontrol grubuna göre anlamlı olarak azaldığı, NAS verilmesi ile düzeylerinin arttığı tespit edildi. Bu çalışmada NAS’ın, CCl4 ile oluşturulan karaciğer hasarındaki oksidatif hasarları onarmada oksijen radikallerini uzaklaştırarak reaktif oksijen türlerinin zararlı etkilerinden korumada yararlı olabileceği ayrıca oksidatif strese karşı dokuların savunmasını destekleyebileceği ve doğrudan antioksidan etki gösterdiği sonucuna varıldı

Keywords

CCl4, N-asetil sistein, glutatyon, lipid peroksidasyonu, rat

References

Adewole SO, Salako AA, Doherty OW, Naicker T (2007): Effect of melatonin on carbon tetrachloride- induced kidney injury in wistar rats. AJBR, 10, 153-164.
Akyol Ö (2004): Şizofrenide oksidatif stres. Kocatepe Tıp Dergisi, 5, 15-25.
Allameh A, Vansoun EY, Zarghi A (1997): Role of glutathione conjugation in protection of weanling rat liver against acetaminophen-induced hepatotoxicity. Mechanisms of Ageing Development, 95, 71-79.
Altomare E, Vendemiale G, Alano O (1988): Hepatic glutathione content in patients with alcoholic and nonalcoholic liver diseases. Life Sci, 43, 991-998.
Angulo P, Lindor KD (2002): Treatment of non-alcoholic steatohepatitis. Best Pract Res Cl Ga, 5, 797-810.
Bray TM, Taylor CG (1994): Enhancement of tissue glutathione for antioxidant and immune functions in malnutrition. Biochemical Pharmacology, 47, 2113-2123.
Candas R, Sohal S, Radyuk SN, Klickhko VI, Orr WC (1997): Molecularorganization of the glutathione reductase gene in Drosophila melanogaster. ABB, 339, 323-334.
Chávez E, Gordillo KR, Segovia J, Shibayama M, Tsutsumi V, Vergara P, Moreno MG, Muriel P (2008): Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J Appl Toxicol, 28, 35–43.
Cnubben NHP, Rıetjens IMCM, Wortelboer H, Van Zanden J, Van Bladeren PJ (2001): The interplay of glutathione-related processes inantioxidant defense. Environmental Toxicology and Pharmacology, 10, 141- 152.
Çakır M (1997): Aspirin ve vitamin E (α-Tokoferol)’nin farelerde (Mus musculus) karaciğer total süperoksit dismutaz ve katalaz aktivitelerine etkileri. Yüksek Lisans Tezi, Ondokuz Mayıs Üniversitesi Biyoloji Anabilim Dalı, Samsun, Türkiye.
Çetinkaya A (2009): Ratlarda N-asetil sistein ve L- karnitin’in karbon tetraklorür ile oluşturulan akut karaciğer hasarı üzerine etkileri. Yan Dal Uzmanlık Tezi. Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Gastroenteroloji Bilim Dalı, Kahramanmaraş, Türkiye.
Düzgüner V (2005): Deneysel olarak diyabet olusturulan tavşanlarda çinkonun lipit peroksidasyonu ve antioksidan sistem üzerine etkisi. Yüksek Lisans Tezi, Mustafa Kemal Üniversitesi Sağlık Bilimleri Enstitüsü, Hatay, Türkiye.
Fairbanks VF, Klee GG (1999): Biochemical aspects of hemotology. In: Burtis CA, Ashwood ER (Eds.), Tietz Textbook of Clinical Chemistry, W.B. Saunders Company, Philadelphia: p. 1642–1710.
Fischer-Nielsen A, Poulsen HE, Hansen BA, Hage E, Keiding S (1991): CCl4 cirrhosis in rats: Irreversible histological changes and differantiated functional impairment. J Hepatol, 12, 110-117.
Gülcen B, Karaca Ö, Kuş MA, Çolakoğlu S, Ögetürk M, Kuş İ (2012): Deneysel karbon tetraklorür zehirlen- mesinde akciğer doku hasarı ve melatonin hormonunun koruyucu rolü: Işık mikroskobik ve biyokimyasal bir çalışma. Düzce Tıp Dergisi, 14, 37-42.
Güven A, Güven A, Gülmez M (2003): The effect of kefir on the activities of GSH-Px, GST, CAT, GSH and LPO levels in carbon tetrachloride-induced mice tissues. J Vet Med B, 50, 412–416.
Güven A, Maraşlı N, Kaya N (2003): Karbon tetraklorür (CCl4) ve etil alkol’ün fare eritrosit antioksidan ve plazma lipid peroksidasyonuna etkisi. Kafkas Üniv Vet Fak Derg, 9, 1-4.
Ichi I, Kamikawaa C, Nakagawaa T, Kobayashia K, Kataokaa R, Nagata E, Kitamuraa Y, Nakazakia C, Matsurab T, Kojoa S (2009): Neutral sphingomyelinase- induced ceramide accumulation by oxidative stres during carbon tetrachloride intoxication. Toxicology, 261, 33–40.
Junqueira LC, Carneiro J, Kelley RO M (1992): Basic Histology. 7nd Ed. New Jersey: Prentice Hill International Inc.
Kang W, Yang H, Hong HJ, Han CH, Lee YJ (2012): Anti-oxidant activities of kiwi fruit extract on carbon tetrachloride-induced liver injury in mice. Korean J Vet Res, 52, 270-280.
Khan MR, Younus T (2011): Prevention of CCl4-induced oxidative damage in adrenal gland by digera muricata extract in rat. Pak J Pharm Sci, 24, 469-473.
Khand FD, Gordge MP, Robertson WG, Noronha- Dutra AA, Hothersall JS (2002): Mitochondrial superoxide production during oxalate mediated oxidative stres in renal epithelial cells. Free Radic Biol Med, 32, 1339-1350.
Kurt H, Basaran A, Aral E (2005): Sıçanlarda karbon tetraklorit’in oluşturduğu oksidatif stresin likopen ile önlenmesi. Türkiye Klinikleri J Med Sci, 25, 167-173.
Liu X, Fu YM, Meadows GG (2011): Differential effects of specific amino acid restriction on glucose metabolism, reduction/oxidation status and mitochondrial damage in DU145 and PC3 prostate cancer cells. Oncology Letters, 2, 349-355.
Loguercio C, Blanco CDV, Coltorti M, Nardi G (1992): Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis. Scand J Clin Lab Invest, 52, 207-213.
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951): Protein measurement with the Folin Phenol Reagent. J Biol Chem, 193, 265-275.
Lu KL, Tsai CC, Ho LK, Lin CC, Chang YS (2002): Preventive effect of the Taiwan folk medicine ixeris laevigata var. Oldhami on a-nophthyl-isothiocyarate and carbon tetrachlorideinduced acute liver injury in rats. Phytother Res, 16, 45-50.
Meister A (1991): Glutathione deficiency produced by inhibition of its synthesis, and its reversal; applications in research and therapy. Pharmacol Therapeut, 51, 155-194.
Memişoğulları R (2005): Diabette serbest radikallerin rolü ve antioksidanların etkisi. Düzce Tıp Fakültesi Dergisi, 3, 30-39.
Roderick P (2004): Liver function tests: defining what’s normal. Brit Med J, 328, 987.
Sun Y, Larry WO, Ying Li (1988): Simple method for clinical assay of superoxide dismutase. Clin Chem, 34, 497-500.
Tanrıverdi G (2005): Karbon tetraklorür (CCl4) ile oluşturulmuş karaciğer hasarında değişik dozlardaki nikotinamidin protektif etkisinin ışık ve elektron mikroskobik olarak incelenmesi. Yüksek Lisans Tezi, İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi Histoloji ve Embriyoloji Anabilim Dalı, İstanbul, Türkiye.
Thrall KD, Vucelick ME, Gies RA, Zangar RC, Weitz KK, Poet TS, Springer DL, Grant DM, Benson JM (2000): Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. J Toxicol Env Heal A, 60, 531-548.
Tietz WN (1987): Measurement of plasma hemoglobin. Fundamental of Clinical Chemistry, Saunders Company; p. 805-806.
Üstündağ B, Bahçecioğlu İH, Şahin K, Gülcü F, Düzgün S, Özercan İH, Gürsu MF (2005): Soy izoflavonların karbon tetraklorüre (CCl4) bağlı karaciğer hasarı ve plazma paraoksonaz ile arilesteraz aktivite düzeylerine olan etkileri. FÜ Sağ Bil Derg, 19, 263-271.
Wong N, Blair AR, Morahan G, Andrikopoulos S (2010): The deletion variant of nicotinamide nucleotide transhydrogenase (nnt) does not affect insulin secretion or glucose tolerance. Endocrinology, 151, 96–102.
Yılmaz S, Bahçecioğlu İH (2000): Karbontetraklorür ile siroz oluşturulmuş ratlarda lipid peroksidasyonu, antioksidant enzim ile piruvat kinaz aktiviteleri. Tr J Vet Anim Sci, 24, 25-28.
Yoshoiko T, Kawada K, Shimada T (1979): Lipid peroxidation in maternal and cord blood and protective mechanism against active oxygen toxicity in the blood. Am J Obstet Gynecol, 135, 372–376.
Yüce A, Aksakal M (2007): Ratların karaciğer ve testis dokusundaki antioksidan aktivite üzerine nar suyunun etkisi. FÜ Sağ Bil Derg, 21, 253-256.
Zafarullah M, Li WQ, Sylvester J, Ahmad M (2003): Molecular mechanisms of Nacetylcysteine actions. Cell Mol Life Sci, 60, 6-20. Geliş tarihi: 20.01.2014 / Kabul tarihi: 24.04.2014

There are 40 citations in total.

Details

Primary Language	English
Subjects	Veterinary Surgery
Other ID	JA75FJ76DT
Journal Section	Research Article
Authors	Hasan Akşit Dilek Akşit Ayşegül Bildik Hatibe Kara Özlem Yavuz Kamil Seyrek
Publication Date	March 1, 2015
Published in Issue	Year 2015Volume: 62 Issue: 1

Cite

APA	Akşit, H., Akşit, D., Bildik, A., Kara, H., et al. (2015). Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 62(1), 1-5. https://doi.org/10.1501/Vetfak_0000002649
AMA	Akşit H, Akşit D, Bildik A, Kara H, Yavuz Ö, Seyrek K. Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication. Ankara Univ Vet Fak Derg. March 2015;62(1):1-5. doi:10.1501/Vetfak_0000002649
Chicago	Akşit, Hasan, Dilek Akşit, Ayşegül Bildik, Hatibe Kara, Özlem Yavuz, and Kamil Seyrek. “Effects of N-Acetyl Cysteine on Glutathione Metabolism and Lipid Peroxidation in the Experimentalhepatic Intoxication”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 62, no. 1 (March 2015): 1-5. https://doi.org/10.1501/Vetfak_0000002649.
EndNote	Akşit H, Akşit D, Bildik A, Kara H, Yavuz Ö, Seyrek K (March 1, 2015) Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication. Ankara Üniversitesi Veteriner Fakültesi Dergisi 62 1 1–5.
IEEE	H. Akşit, D. Akşit, A. Bildik, H. Kara, Ö. Yavuz, and K. Seyrek, “Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication”, Ankara Univ Vet Fak Derg, vol. 62, no. 1, pp. 1–5, 2015, doi: 10.1501/Vetfak_0000002649.
ISNAD	Akşit, Hasan et al. “Effects of N-Acetyl Cysteine on Glutathione Metabolism and Lipid Peroxidation in the Experimentalhepatic Intoxication”. Ankara Üniversitesi Veteriner Fakültesi Dergisi 62/1 (March 2015), 1-5. https://doi.org/10.1501/Vetfak_0000002649.
JAMA	Akşit H, Akşit D, Bildik A, Kara H, Yavuz Ö, Seyrek K. Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication. Ankara Univ Vet Fak Derg. 2015;62:1–5.
MLA	Akşit, Hasan et al. “Effects of N-Acetyl Cysteine on Glutathione Metabolism and Lipid Peroxidation in the Experimentalhepatic Intoxication”. Ankara Üniversitesi Veteriner Fakültesi Dergisi, vol. 62, no. 1, 2015, pp. 1-5, doi:10.1501/Vetfak_0000002649.
Vancouver	Akşit H, Akşit D, Bildik A, Kara H, Yavuz Ö, Seyrek K. Effects of N-acetyl cysteine on glutathione metabolism and lipid peroxidation in the experimentalhepatic intoxication. Ankara Univ Vet Fak Derg. 2015;62(1):1-5.