Research Article
Karbon tetraklorür ile oluşturulan deneysel karaciğer hasarında benfotiamin’in karaciğer dokusu üzerine koruyucu etkilerinin incelenmesi
Abstract
Amaç: Bu çalışmada karbon tetraklorür (CCl4) ile oluşturulan deneysel karaciğer hasarında benfotiaminin karaciğer dokusu üzerine koruyucu etkilerinin incelenmesi amaçlanmıştır.
Gereç ve Yöntem: Çalışmada, 30 adet Wistar albino cinsi erkek sıçanlar kullanıldı. Deney hayvanları 5 eşit gruba ayrıldı. Kontrol grubuna 14 günlük deney süresince herhangi bir uygulama yapılmadı. CCl4 grubuna ise 1. ve 8. günlerde 1ml/kg CCl4: zeytinyağı (1:2) intraperitoneal (i.p) verildi. CCl4 +benfotiamin grubuna 1. ve 8. günlerde iki defa 1 ml/kg CCl4: zeytinyağı (1:2) karışımı ve 70 mg/kg/gün oral benfotiamin verildi. Benfotiamin grubuna 70 mg/kg/gün oral benfotiamin verildi. Zeytinyağı grubuna 1. ve 8. günlerde 2 ml/kg zeytinyağı i.p. olarak verildi. Deney sonunda sıçanlar anestezi altında dekapite edildi. Karaciğer dokuları çıkarılıp incelemeler için parafin bloklar hazırlandı. Ayrıca malondialdehid (MDA) çalışması için dokular – 80 0 C de saklandı.
Bulgular: Kontrol, benfotiamin ve zeytinyağı grupları arasında bakılan parametrelerde anlamlı bir farklılık yoktu. Kontrol grubu ile karşılaştırıldığında CCl4 grubunda, MDA, apoptozis ve bax immünreaktivitesinde anlamlı artış izlendi. CCl4 grubu ile karşılaştırıldığında CCl4 + benfotiamin grubunda ise MDA, apoptozis ve bax immünreaktivitesinde anlamlı azalma görüldü.
Sonuç: CCl4’ün MDA, apoptozis ve bax immünreaktivitesini arttırdığı, tedavi olarak verilen benfotiaminin bu parametreleri azalttığı görüldü.
Keywords
References
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- 2. Dhanabal SP, Syamala G, Satish Kumar MN, Suresh B. Hepatoprotective activity of the Indian medicinal plant Polygala arvensis on D-galactosamine-induced hepatic injury in rats. Fitoterapia 2006; 77: 472-4.
- 3. Naaz F, Javed S, Abdin MZ. Hepatoprotective effect of ethanolic extract of phyllanthus amarus schum et thonn on aflatoxin B1-induced liver damage in mice. J Ethnopharma 2007; 113, 503-9.
- 4. Seven A, Candan G. Antioksidan savunma sistemleri. Cerrahpaşa J Med 1996; 27: 41- 50.
- 5. Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RO. Hepatic lipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest 1983; 71: 429-39.
- 6. Brattin WJ, Glende EA, Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radio Biol Med 1985; 1: 27-38.
- 7. Comporti M. Lipid peroxidation and cellular damage in toxic liver injury. Lab Invest 1985; 53: 599-623.
- 8. Kaplowitz N, Fernandez-Checa J, Ookhtens M. Glutathione, alcohol and hepatotoxicity. Halsted CH, Rucker RB, (Ed). Nutrition and the Origins of Disease. 1st Ed, San Diego: Academic Press, 1989: 267-82.
- 9. Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179-80.
- 10. Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition metals and Disease. Biochem J 1984; 219: 1-14.
- 11. Hooper C. Free radicals: research on biochemical bad boys comes of age. J Natl Inst Health Res 1989; 1: 101-6.
- 12. Slater TF. Free-radical mechanisms in tissue injury. Biochem J 1984; 222: 1-15.
- 13. Musaoğlu A. Karaciğer hastaliklarinda laboratuvar testleri. İliçin G, Ünal S, Biberoğlu K, Akalın S, ve Süleymanlar G (eds). Temel İç Hastalıkları. 1. Baskı, Ankara: Güneş Kitabevi, 1997: 1096-109.
- 14. Recknagel RO, Glende EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharma& Therapeut 1989; 43: 139-54.
- 15. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Critical Reviews in Toxicology 2003; 33: 105-36.
- 16. Yao T, Delgi Esposti S, Huang L, Arnon R, Spangenberger A, Zern MA. Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E. Am J Physiol 1994; 267: 476-84.
- 17. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals in the liver. 2nd Ed, Philadelphia, Lippincott: Williams & Wilkins, 1999.
- 18. Poli G, Cottalasso D, Pronzato MA, Chiarpotto E, Marinari UM. Lipid peroxidation and covalent binding in the early functional impairment of golgi apparatus by carbon tetrachloride. Cell Biochem Funct 1990; 8: 1–10.
- 19. Poli G, Albano E, Dianzano MU. The role of lipid peroxidation in liver damage. Chem Phys Lipids 1987; 45: 117–42.
- 20. Woelk H, Lehrl S, Bitsch R, Kopcke W. Benfotiamine in treatment of alcoholic polineuropathy; an 8-week randomized controlled study (BAPI Study). Alcohol 1998; 33: 318-631.
- 21. Gadau S, Emanueli C, Linthout SV, Grainai G, Todaro M, Meloni M, et al. Benfothiamine accelerate the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia 2006; 49: 405-20.
- 22. Marchetti V, Menghinni R, Rizza S, ve ark. Benfothiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/ FOXOsignaling. Diabetes 2006; 55: 2231-37.
- 23. Bakker SJ, Heine RJ, Gans RO. Thiamine may indirectly act as an antioxidant. Diabetologia 1997; 40: 741-2.
- 24. Pomero F, Molinar Min A, La Selva M, Allione A, Molinetti GM, Porta M. Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose. Acta Diabetal 2001; 38: 135-8.
- 25. Orrego H, Blake JE, Blendis LM, Medline A. Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis. Gastroenterology 1987; 92: 208-14.
- 26. Ning QJ, Qin SW, Xu CS. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration. World J Gastroenterol 2006; 21: 6966-72.
- 27. Cabre M, Comps J, Paternain JL, Ferre N, Joven J. Time course of changes in hepatic lipid peroxidation and glutathione metabolism in ratswith carbon tetrachloride-induced cirrhosis. Clin Exp Pharmacol Physiol 2000; 27: 694-9.
- 28. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr 2001; 85: 67-74.
- 29. Ökten A. Türkiye’de karaciger sirozunun etyolojisi. Hepotolojide Güncel Gelişmeler Sempozyum Kitabı, 1998: 67.
- 30. Wang H, Wei W, Wang NP. Melatonin ameliorates carbontetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stres. Life Sci 2005; 77: 1902-15.
- 31. Parola M, Robino G. Oxidative stress-related molecules and liver fibrozis. J Hepatolog 2001; 35: 297-306.
- 32. Poli G. Pathogenesis of liver fibrozis, role of oxidative stres. Moleculer Aspects of Medicine 2000; 21: 49-98.
- 33. Lee KS, Buck M, Houglum K. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stres through Cyb expression. J Clin Invest 1995; 96: 2461-8.
- 34. Parola M, Pinzani M, Casini A. Stimulation of lipid peroxidation or 4- hdroxynonenal treatment increase procollagen alpha 1 (I) gene expression in human liver fat- storing cells. Biochem Biophysical Res Comm 1993; 194: 1044-50.
- 35. Kumar V, Cotran RS, Robbins SL. Temel Patoloji. Çevikbas U (Ed). 2. Baskı, İstanbul: Nobel Tıp Kitapevleri, 1994: 545-50.
- 36. Gochee PA, Johnsson JR, Clouston AD. Steatozis in Chronic Hepatitis C: association with increased Messenger RNA Expression of Collagen I, tumor necrosis factor-alpha and cytochrome P450 2E1. J Gastro Hepatolog 2003; 18: 386-92.
- 37. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr 2001; 2: 67-74.
- 38. Castillo T, Koop DR, Kamimura S, Triadafilopoulos G, Tsukamodo H. Role of cytochrome P-450 2E in ethanol-carbon tetrachloride-and iron-dependent microsomal lipidperoxidation. Hepatology 1992; 16: 992–6.
- 39. Hartley DP, Kolaja KL, Reinchord J, Peterson DR. 4-Hydroxynonenal and malondialdehyde hepatic protein adducts in rats treated with carbon tetrachloride: immunochemical detectionand lobular localization. Toxicol Appl Pharmacol 1999; 161: 23–33. 40. Oren M, Rotter V. Introduction: p53 the first twenty years. Cell Mol Life Sci 1999; 55: 9-11.
- 41. Bandyopadhyay U, Das D, Banerjee R. Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci 1999; 77: 658-65. 42. Pietta P G. Flavonoids as antioxidants. J Nat Prod 2000; 63; 1035-42. 43. Mc Gee SA, Wiggins SA, Pierce JD. What advanced practise nurses to know about free radicals. İnt J Adv Nurs Prac 2003; 6: 1-10. 44. Hong RT, Xu JM, Mei Q. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats. World J Gastroenterol 2009; 15: 1452-8.
- 45. Guven A, Gulmez M. 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 2003; 50: 412–6.
- 46. Halliwell B Antioxidant characterization. Methodology and mechanism. Biochem Pharma 1995; 49: 1341-8.
- 47. Burçak G, Andrican G. Oksidatif DNA hasarı ve yaşlanma. Cerrahpaşa Tıp Dergisi 2004;12: 159-69.
- 48. Ellis RE, Yuan J, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol 1991; 7: 663-98.
- 49. Chin PL, Momand J, Pfeifer GP. In vivo evidence for binding of p53 to consensus binding sites in the p21 and GADD45 genes in response to ionizing radiation. Oncogene 1997; 15: 87-100.
- 50. Nagata S. Apoptosis by death factor. Cell 1997; 88: 355-65.
- 51. Lee JI, Lee KS, Paik YH, ve ark. Apoptosis of hepatic stellate cells in carbon tetrachloride induced acute liver injury of the rat: analysis of isolated hepatic stellate cells. J Hepatol 2003; 39: 960-6.
- 52. Hoijman E, Rocha Viegas L, Keller Sarmiento MI, Rosenstein RE, Pecci A. Involvement of bax protein in the prevention of glucocorticoid-induced thymocytes apoptosis by melatonin. Endocrinology 2004; 145: 418-25.
- 53. Valles EG, de Castro CR, Castro JA. N-acetlylcysteine is an early but also a late preventive agent aganist carbon tetrachloride induced liver necrosis TOXİCOL Lett 1994; 71: 87-95.
- 54. Bayram İ. Askorbik asit ve alfa-tokoferol’ün karbon tetraklorürle oluşturulmuş akut karaciğer toksisitesi modelinde karaciğeri koruyucu etkisi. Van Tıp Dergisi 2004; 11: 32-8.
- 55. Üstündağ B, Bahçecioğlu İH, Şahin K ve ark. Soy izoflavonların karbon tetraklorüre (CCl4) bağlı karaciğer hasarı ve plazma paraoksonaz ile arilesteraz aktivite düzeylerine olan etkileri. FÜ Sağlık Bil Dergisi 2005; 19: 263-71.
Investigation of benfotiamine’s protective effects on liver tissue in experimental carbon tetrachloride induced liver injury
Abstract
Purpose: In this study, we aimed to investigate the protective effects of benfotiamine on experimental liver injury caused by carbon tetrachloride (CCl4).
Materials and Methods: In this study, 30 male Wistar albino rats were used. Rats were equally divided into 5 groups. No application was made to control group. The CCl4 group was injected i.p with1ml/kg CCl4:olive oil (1:2) mixture on the 1st and 8th days, and the CCl4+benfotiamine group was treated i.p with 1 ml/kg CCl4: olive oil (1:2) mixture twice on the 1st and 8th days and orally with 70 mg/kg/day benfotiamine. To the benfotiamine group, 70 mg/kg/day benfotiamine was given orally for 14 days. To the olive oil group, 2 ml/kg olive oil was given i.p. on 1st and 8th days. Finally, rats were decapitated. Liver tissues were removed and paraffin blocks were prepared. Tissues were stored at –80 oC for malonaldeyhde (MDA) assay.
Results: There were no significant differences between the control, benfotiamine and olive oil groups. Compared with the control group, there was a significant increase in MDA, apoptosis and bax immunoreactivity in CCl4 group. Compared with the CCl4 group, there was a significant decrease in MDA, apoptosis and bax immunoreactivity in the CCl4+benfotiamine group.
Conclusion: CCl4 increases MDA, apoptosis and bax immunoreactivity, and benfotiamine, given as treatment, reduces these parameters.
Keywords
References
- 1. Burroughs AK, Westaby D. Liver, biliary tract and pancreatic disease. Kumar P, Clark M (Eds). Clinical Medicine (6th ed), Elsevier Saunders, 2005: 347-417.
- 2. Dhanabal SP, Syamala G, Satish Kumar MN, Suresh B. Hepatoprotective activity of the Indian medicinal plant Polygala arvensis on D-galactosamine-induced hepatic injury in rats. Fitoterapia 2006; 77: 472-4.
- 3. Naaz F, Javed S, Abdin MZ. Hepatoprotective effect of ethanolic extract of phyllanthus amarus schum et thonn on aflatoxin B1-induced liver damage in mice. J Ethnopharma 2007; 113, 503-9.
- 4. Seven A, Candan G. Antioksidan savunma sistemleri. Cerrahpaşa J Med 1996; 27: 41- 50.
- 5. Bacon BR, Tavill AS, Brittenham GM, Park CH, Recknagel RO. Hepatic lipid peroxidation in vivo in rats with chronic iron overload. J Clin Invest 1983; 71: 429-39.
- 6. Brattin WJ, Glende EA, Recknagel RO. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radio Biol Med 1985; 1: 27-38.
- 7. Comporti M. Lipid peroxidation and cellular damage in toxic liver injury. Lab Invest 1985; 53: 599-623.
- 8. Kaplowitz N, Fernandez-Checa J, Ookhtens M. Glutathione, alcohol and hepatotoxicity. Halsted CH, Rucker RB, (Ed). Nutrition and the Origins of Disease. 1st Ed, San Diego: Academic Press, 1989: 267-82.
- 9. Halliwell B. The antioxidant paradox. Lancet 2000; 355: 1179-80.
- 10. Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition metals and Disease. Biochem J 1984; 219: 1-14.
- 11. Hooper C. Free radicals: research on biochemical bad boys comes of age. J Natl Inst Health Res 1989; 1: 101-6.
- 12. Slater TF. Free-radical mechanisms in tissue injury. Biochem J 1984; 222: 1-15.
- 13. Musaoğlu A. Karaciğer hastaliklarinda laboratuvar testleri. İliçin G, Ünal S, Biberoğlu K, Akalın S, ve Süleymanlar G (eds). Temel İç Hastalıkları. 1. Baskı, Ankara: Güneş Kitabevi, 1997: 1096-109.
- 14. Recknagel RO, Glende EA, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharma& Therapeut 1989; 43: 139-54.
- 15. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Critical Reviews in Toxicology 2003; 33: 105-36.
- 16. Yao T, Delgi Esposti S, Huang L, Arnon R, Spangenberger A, Zern MA. Inhibition of carbon tetrachloride-induced liver injury by liposomes containing vitamin E. Am J Physiol 1994; 267: 476-84.
- 17. Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals in the liver. 2nd Ed, Philadelphia, Lippincott: Williams & Wilkins, 1999.
- 18. Poli G, Cottalasso D, Pronzato MA, Chiarpotto E, Marinari UM. Lipid peroxidation and covalent binding in the early functional impairment of golgi apparatus by carbon tetrachloride. Cell Biochem Funct 1990; 8: 1–10.
- 19. Poli G, Albano E, Dianzano MU. The role of lipid peroxidation in liver damage. Chem Phys Lipids 1987; 45: 117–42.
- 20. Woelk H, Lehrl S, Bitsch R, Kopcke W. Benfotiamine in treatment of alcoholic polineuropathy; an 8-week randomized controlled study (BAPI Study). Alcohol 1998; 33: 318-631.
- 21. Gadau S, Emanueli C, Linthout SV, Grainai G, Todaro M, Meloni M, et al. Benfothiamine accelerate the healing of ischaemic diabetic limbs in mice through protein kinase B/Akt-mediated potentiation of angiogenesis and inhibition of apoptosis. Diabetologia 2006; 49: 405-20.
- 22. Marchetti V, Menghinni R, Rizza S, ve ark. Benfothiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/ FOXOsignaling. Diabetes 2006; 55: 2231-37.
- 23. Bakker SJ, Heine RJ, Gans RO. Thiamine may indirectly act as an antioxidant. Diabetologia 1997; 40: 741-2.
- 24. Pomero F, Molinar Min A, La Selva M, Allione A, Molinetti GM, Porta M. Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose. Acta Diabetal 2001; 38: 135-8.
- 25. Orrego H, Blake JE, Blendis LM, Medline A. Prognosis of alcoholic cirrhosis in the presence and absence of alcoholic hepatitis. Gastroenterology 1987; 92: 208-14.
- 26. Ning QJ, Qin SW, Xu CS. Expression patterns and action analysis of genes associated with drug-induced liver diseases during rat liver regeneration. World J Gastroenterol 2006; 21: 6966-72.
- 27. Cabre M, Comps J, Paternain JL, Ferre N, Joven J. Time course of changes in hepatic lipid peroxidation and glutathione metabolism in ratswith carbon tetrachloride-induced cirrhosis. Clin Exp Pharmacol Physiol 2000; 27: 694-9.
- 28. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr 2001; 85: 67-74.
- 29. Ökten A. Türkiye’de karaciger sirozunun etyolojisi. Hepotolojide Güncel Gelişmeler Sempozyum Kitabı, 1998: 67.
- 30. Wang H, Wei W, Wang NP. Melatonin ameliorates carbontetrachloride-induced hepatic fibrogenesis in rats via inhibition of oxidative stres. Life Sci 2005; 77: 1902-15.
- 31. Parola M, Robino G. Oxidative stress-related molecules and liver fibrozis. J Hepatolog 2001; 35: 297-306.
- 32. Poli G. Pathogenesis of liver fibrozis, role of oxidative stres. Moleculer Aspects of Medicine 2000; 21: 49-98.
- 33. Lee KS, Buck M, Houglum K. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stres through Cyb expression. J Clin Invest 1995; 96: 2461-8.
- 34. Parola M, Pinzani M, Casini A. Stimulation of lipid peroxidation or 4- hdroxynonenal treatment increase procollagen alpha 1 (I) gene expression in human liver fat- storing cells. Biochem Biophysical Res Comm 1993; 194: 1044-50.
- 35. Kumar V, Cotran RS, Robbins SL. Temel Patoloji. Çevikbas U (Ed). 2. Baskı, İstanbul: Nobel Tıp Kitapevleri, 1994: 545-50.
- 36. Gochee PA, Johnsson JR, Clouston AD. Steatozis in Chronic Hepatitis C: association with increased Messenger RNA Expression of Collagen I, tumor necrosis factor-alpha and cytochrome P450 2E1. J Gastro Hepatolog 2003; 18: 386-92.
- 37. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr 2001; 2: 67-74.
- 38. Castillo T, Koop DR, Kamimura S, Triadafilopoulos G, Tsukamodo H. Role of cytochrome P-450 2E in ethanol-carbon tetrachloride-and iron-dependent microsomal lipidperoxidation. Hepatology 1992; 16: 992–6.
- 39. Hartley DP, Kolaja KL, Reinchord J, Peterson DR. 4-Hydroxynonenal and malondialdehyde hepatic protein adducts in rats treated with carbon tetrachloride: immunochemical detectionand lobular localization. Toxicol Appl Pharmacol 1999; 161: 23–33. 40. Oren M, Rotter V. Introduction: p53 the first twenty years. Cell Mol Life Sci 1999; 55: 9-11.
- 41. Bandyopadhyay U, Das D, Banerjee R. Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci 1999; 77: 658-65. 42. Pietta P G. Flavonoids as antioxidants. J Nat Prod 2000; 63; 1035-42. 43. Mc Gee SA, Wiggins SA, Pierce JD. What advanced practise nurses to know about free radicals. İnt J Adv Nurs Prac 2003; 6: 1-10. 44. Hong RT, Xu JM, Mei Q. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats. World J Gastroenterol 2009; 15: 1452-8.
- 45. Guven A, Gulmez M. 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 2003; 50: 412–6.
- 46. Halliwell B Antioxidant characterization. Methodology and mechanism. Biochem Pharma 1995; 49: 1341-8.
- 47. Burçak G, Andrican G. Oksidatif DNA hasarı ve yaşlanma. Cerrahpaşa Tıp Dergisi 2004;12: 159-69.
- 48. Ellis RE, Yuan J, Horvitz HR. Mechanisms and functions of cell death. Annu Rev Cell Biol 1991; 7: 663-98.
- 49. Chin PL, Momand J, Pfeifer GP. In vivo evidence for binding of p53 to consensus binding sites in the p21 and GADD45 genes in response to ionizing radiation. Oncogene 1997; 15: 87-100.
- 50. Nagata S. Apoptosis by death factor. Cell 1997; 88: 355-65.
- 51. Lee JI, Lee KS, Paik YH, ve ark. Apoptosis of hepatic stellate cells in carbon tetrachloride induced acute liver injury of the rat: analysis of isolated hepatic stellate cells. J Hepatol 2003; 39: 960-6.
- 52. Hoijman E, Rocha Viegas L, Keller Sarmiento MI, Rosenstein RE, Pecci A. Involvement of bax protein in the prevention of glucocorticoid-induced thymocytes apoptosis by melatonin. Endocrinology 2004; 145: 418-25.
- 53. Valles EG, de Castro CR, Castro JA. N-acetlylcysteine is an early but also a late preventive agent aganist carbon tetrachloride induced liver necrosis TOXİCOL Lett 1994; 71: 87-95.
- 54. Bayram İ. Askorbik asit ve alfa-tokoferol’ün karbon tetraklorürle oluşturulmuş akut karaciğer toksisitesi modelinde karaciğeri koruyucu etkisi. Van Tıp Dergisi 2004; 11: 32-8.
- 55. Üstündağ B, Bahçecioğlu İH, Şahin K ve ark. Soy izoflavonların karbon tetraklorüre (CCl4) bağlı karaciğer hasarı ve plazma paraoksonaz ile arilesteraz aktivite düzeylerine olan etkileri. FÜ Sağlık Bil Dergisi 2005; 19: 263-71.
There are 51 citations in total.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Research |
| Authors | |
| Publication Date | June 30, 2020 |
| Acceptance Date | April 13, 2020 |
| Published in Issue | Year 2020 Volume: 45 Issue: 2 |
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