Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity

ATASEVER, Ayhan; DINCEL, Gungor Cagdas; YAMAN, Duygu

Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity

Güngör Çağdaş DİNÇEL, (Aksaray Üniversitesi, Eskil Meslek Yüksekokulu, Laboratuvar ve Veterinerlik Sağlık Programı, Aksaray, Türkiye)

Ayhan ATASEVER, (Erciyes Üniversitesi, Veteriner Fakültesi, Patoloji Anabilim Dalı, Ankara, Türkiye)

Duygu YAMAN (Erciyes Üniversitesi, Veteriner Fakültesi, Patoloji Anabilim Dalı, Ankara, Türkiye)

Kafkas Üniversitesi Veteriner Fakültesi Dergisi

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Yıl: 2016 Cilt: 22 Sayı: 5 Sayfa Aralığı: 671 - 678 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity

Öz:

Karbon tetraklorür (CCl4) karaciğerde nekroz ve fibrozis meydana getirerek siroza ve karaciğer yetmezliğine neden olabilmektedir. Günümüzde karaciğer fibrozis mekanizmasının anlaşılmasına yönelik çok fazla çalışma olmasına rağmen, oluşum mekanizması ile ilgili moleküler düzeydeki bilgiler hala eksiktir. Bu çalışmada CCl4 ile hepatotoksisite oluşturulan erkek Wistar albino sıçanlarda fibrozisin oluşum aşamasında nitric oksit (NO) ve glial fibriller asidik protein (GFAP) etkilerinin araştırılması ve altında yatan mekanizmanın aydınlatılması amaçlanmıştır. Çalışmada 20 adet erkek sıçan, her grupta toplam 10 sıçan olmak üzere sağlıklı kontrol grubu (A) ve CCl4 ile oluşturulan karaciğer fibrozu grubu (B) olarak rastgele ikiye ayrıldı. Histolojik ve immunohistokimyasal analizlerle CCl4 grubunda yangısal değişiklikler ile karaciğer nekroz/fibrozis tespit edildi. On iki hafta süreyle CCl4 verilerek oluşturulan karaciğer hasarının oluşumunda, indüklenebilen ve endotelyal NO sentazın (P<0.05) yüksek sunumlarına bağlı olarak artan NO üretiminin önemli bir rol oynadığı belirlendi. Ayrıca, CCl4 grubunda karaciğerde GFAP (P<0.05) sunumlarında önemli artış da gösterildi. Sonuç olarak, CCl4 kaynaklı karaciğer hasarı ve fibrozisin gelişiminde NO ve GFAP'ın önemli bir rol oynadığı tespit edildi.

Anahtar Kelime:

Konular: Veterinerlik

Karbon Tetraklorür İle Oluşturulan Hepatotoksisite Karaciğer Paranşimindeki Nitrik Oksit ve Gliyal Fibriller Asidik Protein (GFAP) Sunumları

Öz:

Carbon tetrachloride (CCl4)-induced liver injury causes necrosis and fibrosis, which may lead to cirrhosis and liver failure. Although a lot of study to understand the mechanism of liver fibrosis, our knowledge of the molecular level of this disease is still incomplete. The aim of this study was to investigate the effect and regulation of nitric oxide (NO) and glial fibrillary acidic protein (GFAP) on the severity of hepatic injury in male Wistar albino rats with CCl4-induced hepatotoxicity and elucidate the underlying mechanism. A total of 20 male rats were randomly divided into healthy control group (A) and CCl4-induced hepatic fibrosis model group (B), with 10 rats in each group. The results of this study suggest CCl4-induced hepatic injury is mediated by excessive NO production and up-regulated by inducible and endothelial NO synthase (P<0.05), which may plays a role in increasing hepatic injury. Additionally, liver injury induced by CCl4 demonstrated significant increases in GFAP (P<0.05). Histological and immunohistochemical analyses of the CCl4-treated group exhibited increased inflammatory process and liver necrosis/fibrosis. Inflammatory response especially NO and GFAP expression is identified to play an important role in the development of liver injury and fibrosis induced by CCl4.

Anahtar Kelime:

Konular: Veterinerlik

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Weber LW, Boll M, Stampfl A: Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. CRC Crit RevToxicol, 33, 105-136, 2003. DOI: 10.1080/713611034
2. Ahn M, Park JS, Chae S, Kim S, Moon C, Hyun JW, Shin T: Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats. Acta Histochem, 116, 1104-1112, 2014. DOI: 10.1016/j.acthis.2014.05.004
3. Clawson G: Mechanisms of carbon tetrachloride hepatotoxicity. PatholImmunopath Res, 8, 104-112, 1989. DOI: 10.1159/000157141
4. Perez Tamayo R: Is cirrhosis of the liver experimentally producedby CCl4 and adequate model of human cirrhosis? Hepatology, 3, 112-120, 1983. DOI: 10.1002/hep.1840030118
5. Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH, Lee SM: Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull, 30, 1898-1904, 2007. DOI: 10.1248/bpb.30.1898
6. Yang YS, Ahn TH, Lee JC, Moon CJ, Kim SH, Jun W, Park SC, Kim HC, Kim JC: Protective effects of pycnogenol on carbon tetrachlorideinduced hepatotoxicity in Sprague-Dawley rats. Food Chem Toxicol, 46, 380-387, 2008. DOI: 10.1016/j.fct.2007.08.016
7. Geller DA, Lowenstein CJ, Shapiro RA, Nussler AK, Di Silvio M, Wang SC, Nakayama DK, Simmons RL, Snyder SH, Billiar TR: Molecular cloning and expression of inducible nitric oxide synthase from human hepatocytes. Proc Natl Acad Sci USA, 90, 3491-3495, 1993. DOI: 10.1073/ pnas.90.8.3491
8. Laskin DL, Heck DE, Gardner CR, Feder LS, Laskin JD: Distinct patterns of nitric oxide production in hepatic macrophages and endothelial cells following acute exposure of rats to endotoxin. J Leukoc Biol, 56, 751- 758, 1994.
9. Lang D, Lewis MJ: Biochemical effects of nitric oxide on vascular smooth muscle. In, Mathie RT, Griffith TM (Eds): The Haemodynamic Effects of Nitric Oxide, 3-21, 1st ed., Imperial College Press, London, 1999.
10. Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC: Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature, 377, 239-242, 1995. DOI: 10.1038/377239a0
11. Clemens MG: Nitric oxide in the liver. In, Arias IM, Boyer JL, Chisari FV, Fausto N, Schachter D, Shafritz DA (Eds): The Liver: Biology and Pathobiology. Fourth ed., 4-18, Lippincott Williams & Wilkins, Philadelphia, 2001.
12. Moncada S, Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med, 329, 2002-2012, 1993. DOI: 10.1056/NEJM199312303292706
13. Helyar L, Bundschuh DS, Laskin JD, Laskin DL: Induction of hepatic Ito cell nitric oxide production after acute endotoxemia. Hepatology, 6, 1509-1515, 1994. DOI: 10.1002/hep.1840200621
14. Zhu W, Fung PC: The roles played by crucial free radicals like lipid free radicals, nitric oxide, and enzymes NOS and NADPH in CCl(4)- induced acute liver injury of mice. Free Radic Biol Med, 29, 870-880, 2000. DOI: 10.1016/S0891-5849(00)00396-8
15. Chamulitrat W, Jordan SJ, Mason RP: Nitric oxide production during endotoxic shock in carbon tetrachloride-treated rats. Mol Pharmacol, 46, 391-397, 1994.
16. Oshita M, Takei Y, Kawano S, Hijioka T, Masuda E, Goto M, Nishimura Y, Nagai H, Iio S, Tsuji S: Endogenous nitric oxide attenuates ethanol-induced perturbation of hepatic circulation in the isolated perfused rat liver. Hepatology, 20, 961-965, 1994. DOI: 10.1002/hep.1840200427
17. Tanaka N, Tanaka K, Nagashima Y, Kondo M, Sekihara H: Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachlorideinduced acute hepatic injury. Gastroenterology, 117, 173-180, 1999. DOI: 10.1016/S0016-5085(99)70565-2
18. Morio LA, Chiu H, Sprowles KA, Zhou P, Heck DE, Gordon MK, Laskin DL: Distinct roles of tumor necrosis factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol, 172, 44-51, 2001. DOI: 10.1006/taap.2000.9133
19. Jacque CM, Vinner C, Kujas M, Raoul M, Racadot J, Baumann NA: Determination of glial fibrillary acidic protein (GFAP) in human brain tumors. J Neurol Sci, 35, 147-155, 1978. DOI: 10.1016/0022-510X(78)90107-7
20. Eng L, Ghirnikar R: GFAP and astrogliosis. Brain Pathol, 4, 229-237, 1994. DOI: 10.1111/j.1750-3639.1994.tb00838.x
21. Gard A, White F, Dutton G: Extra-neural glial fibrillary acidic protein (GFAP) immunoreactivity in perisinusoidal stellate cells of rat liver. J Neuroimmunol, 8, 359-375, 1985. DOI: 10.1016/S0165-5728(85)80073-4
22. Buniatian G, Traub P, Albinus M, Beckers G, Buchmann A, Gebhardt R, Osswald H: The immunoreactivity of glial fibrillary acidic protein in mesangial cells and podocytes of the glomeruli of rat kidney in vivo and in culture. Biol Cell, 90, 53-61, 1998. DOI: 10.1016/S0248-4900(98) 80232-3
23. Apte MV1, Haber PS, Applegate TL, Norton ID, McCaughan GW, Korsten MA, Pirola RC, Wilson JS: Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture. Gut, 43, 128-133, 1998. DOI: 10.1136/gut.43.1.128
24. Friedman SL: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem, 275, 2247-2250, 2000. DOI: 10.1074/jbc.275.4.2247
25. Tennakoon AH, Izawa T, Wijesundera KK, Golbar HM, Tanaka M, Ichikawa C, Kuwamura M, Yamate J: Characterization of glial fibrillary acidic protein (GFAP)-expressing hepatic stellate cells and myofibroblasts in thioacetamide (TAA)-induced rat liver injury. Exp Toxicol Pathol, 65, 1159-1171, 2013. DOI: 10.1016/j.etp.2013.05.008
26. Li T, Leng XS, Zhu JY, Wang FS: Establishment and characterization of an immortalized rat hepatic stellate cell line. Int J Clin Exp Pathol, 8, 12064-12074, 2015.
27. Dincel GC, Yildirim S: Overexpression of ADAMTS-13 and neuronal nitric oxide synthase relates with neuropathology in streptozotocininduced type 1 diabetic rats. Int J Clin Exp Pathol, 9, 4761-4778, 2016.
28. Dincel GC, Atmaca HT: Role of oxidative stress in the pathophysiology of Toxoplasma gondii infection. Int J Immunopathol Pharmacol, 29, 226- 234, 2016. DOI: 10.1177/0394632016638668
29. Li JT, Liao ZX, Ping J, Xu D, Wang H: Molecular mechanism of hepatic stellate cell activation and antifibrotic therapeutic strategies. J Gastroenterol, 43, 419-428, 2008. DOI: 10.1007/s00535-008-2180-y
30. Chamulitrat W, Blazka ME, Jordan SJ, Luster MI, Mason RP: Tumor necrosis factor-? and nitric oxide production in endotoxin-primed rats administered carbon tetrachloride. Life Sci, 57, 2273-2280, 1995. DOI: 10.1016/0024-3205(95)02220-D
31. Tilg H, Diehl AM: Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med, 343, 1467-1476, 2000. DOI: 10.1056/ NEJM200011163432007
32. Poli G: Pathogenesis of liver fibrosis: Role of oxidative stress. Mol Aspects Med, 21, 49-98, 2000. DOI: 10.1016/S0098-2997(00)00004-2
33. Przybocki JM, Reuhl KR, Thurman RG, Kauffman FC: Involvement of nonparenchymal cells in oxygen-dependent hepatic injury by allyl alcohol. Toxicol Appl Pharmacol, 115, 57-63, 1992. DOI: 10.1016/0041-008X(92) 90367-2
34. Edwards MJ, Keller BJ, Kauffman FC, Thurman RG: The involvement of Kupffer cells in carbon tetrachloride toxicity. Toxicol Appl Pharmacol, 119, 275-279, 1993. DOI: 10.1006/taap.1993.1069
35. Adachi Y, Bradford BU, Gao W, Bojes HK: Thurman RG.Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology, 20, 453-460, 1994. DOI: 10.1002/hep.1840200227
36. Decker K: Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem, 192(2), 245-261, 1990. DOI: 10.1111/j.1432- 1033.1990.tb19222.x
37. Förstermann U, Schmidt HH, Pollock JS, Sheng H, Mitchell JA, Warner TD, Nakane M, Murad F: Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol, 42, 1849-1857, 1991. DOI: 10.1016/0006-2952(91)90581-O

APA	DINCEL G, ATASEVER A, YAMAN D (2016). Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. , 671 - 678.
Chicago	DINCEL Gungor Cagdas,ATASEVER Ayhan,YAMAN Duygu Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. (2016): 671 - 678.
MLA	DINCEL Gungor Cagdas,ATASEVER Ayhan,YAMAN Duygu Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. , 2016, ss.671 - 678.
AMA	DINCEL G,ATASEVER A,YAMAN D Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. . 2016; 671 - 678.
Vancouver	DINCEL G,ATASEVER A,YAMAN D Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. . 2016; 671 - 678.
IEEE	DINCEL G,ATASEVER A,YAMAN D "Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity." , ss.671 - 678, 2016.
ISNAD	DINCEL, Gungor Cagdas vd. "Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity". (2016), 671-678.

APA	DINCEL G, ATASEVER A, YAMAN D (2016). Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 22(5), 671 - 678.
Chicago	DINCEL Gungor Cagdas,ATASEVER Ayhan,YAMAN Duygu Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. Kafkas Üniversitesi Veteriner Fakültesi Dergisi 22, no.5 (2016): 671 - 678.
MLA	DINCEL Gungor Cagdas,ATASEVER Ayhan,YAMAN Duygu Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, vol.22, no.5, 2016, ss.671 - 678.
AMA	DINCEL G,ATASEVER A,YAMAN D Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2016; 22(5): 671 - 678.
Vancouver	DINCEL G,ATASEVER A,YAMAN D Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity. Kafkas Üniversitesi Veteriner Fakültesi Dergisi. 2016; 22(5): 671 - 678.
IEEE	DINCEL G,ATASEVER A,YAMAN D "Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity." Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 22, ss.671 - 678, 2016.
ISNAD	DINCEL, Gungor Cagdas vd. "Nitric Oxide and Glial Fibrillary Acidic Protein (GFAP) Expression in the Liver Parenchyma in Carbon Tetrachloride-Induced Hepatotoxicity". Kafkas Üniversitesi Veteriner Fakültesi Dergisi 22/5 (2016), 671-678.