Karaciğer Fibrozis Modellerinde Sık Kullanılan Kimyasal Ajanların Farklı Doz ve Zaman Dilimindeki Etkilerinin Belirlenmesi
Abstract
Amaç: Bu çalışmada, karbon tetraklorür ve tiyoasetamid (CCl4 ve TAA) modellerinde alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), albümin, trigliserit ve kolesterol gibi biyokimyasal parametreler ve histopatolojik özellikler değerlendirilerek doz ve zamana bağlı olarak daha etkin modelin ortaya çıkarılması amaçlanmıştır.
Yöntem: Her bir model için ratlar 3 gruba ayrılmıştır ve intraperitoneal (i.p.) olarak CCl4 (0.5 ml/kg, 1.0 ml/kg, 2.0 ml/kg) ve TAA (100 mg/kg, 200 mg/kg, 300 mg/kg) 4, 6 ve 8 hafta boyunca hafta da üç kez enjeksiyon yapılmıştır.
Bulgular: Biyokimyasal araştırmalar sonucunda ALT ve AST değerleri, sadece 0,5 ml CCL4 6. ve 8. hafta gruplarında kontrol gruplarına göre istatistiksel olarak anlamlı fark göstermiştir (p<0.05). Diğer biyokimyasal parametrelerin değerleri kalan gruplar arasında anlamlı farklılık göstermemiştir (p>0.05). Histopatolojik sonuçlara
bakıldığında karaciğer dokusunda, kontrol gruplarının her ikisinde de karaciğer, normal histolojik yapısını göstermiştir. Diğer bütün gruplarda, artan zaman ve doza bağlı olarak her iki modelde göze çarpan hepatofibrotik değişiklikler gözlemlenmiştir.
Sonuç: Doz ve zamana bağlı olarak sekizinci haftaya ulaşan gruplarda siroz geliştiği gözlemlenmiştir. Bu sonuçlar hepatofibrotik çalışmalar için yarayışlı birer referans olabilecektir.
Supporting Institution
Erciyes Üniversitesi
Project Number
TSA-2016-6571
Thanks
Genom ve Kök Hücre Merkezine teşekkür ederiz.
References
- 1. Anthony PP, Ishak KG, Nayak NC, Poulsen HE, Scheuer PJ, Sobin LH. The morphology of cirrhosis: definition, nomenclature, and classification. Bull World Health Organ 1977;55(4):521–540. PMID 304393
- 2. Koh C, Heller T. Approach to the diagnosis of portal hypertension. Theo Heller. 2012;1(5): 133-135. DOI: 10.1002/cld.00078
- 3. Floreanı A, Cazzagon N, Martines D, Cavalletto L, Baldo V, Chemello L. Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis. Dig Liver Dis. 2011;43(11):887-892. DOI: 10.1016/j.dld.2011.06.011
- 4. Poupon R, Corpechot C. Elastography-based assessment of primary biliary cirrhosis staging. Dig Liver Dis. 2011;3(11):839-840. DOI: 10.1016/j.dld.2011.08.001
- 5. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol. 2011; 6:425–456. DOI: 10.1146/annurev-pathol-011110-130246
- 6. Popov Y, Schuppan D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies. Hepatology. 2009;50(4):1294–1306. DOI: 10.1002/hep.23123
- 7. Park HJ, Kim HG, Wang JH, Choi MK, Han JM, Lee JS, Son CG. Comparison of TGF-b, PDGF, and CTGF in hepatic fibrosis models using DMN, CCl4, and TAA. Drug Chem Toxicol. 2016;39(1):111–118. DOI: 10.3109/01480545.2015.1052143
- 8. Fortea JI, Fernández-Mena C, Puerto M, Ripoll C, Almagro J, Bañares J, et al. Comparison of two protocols of carbon tetrachloride-induced cirrhosis in rats - improving yield and reproducibility. Sci Rep 2018;8:1–10. DOI:10.1038/s41598-018-27427-9
- 9. Akhtar T, Sheikh N. An overview of thioacetamide-induced hepatotoxicity. Toxin Rev 2013;32:43–46 DOI: 10.3109/15569543.2013.805144
- 10. Iredale JP. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest. 2007;117(3):539–548. DOI: 10.1172/JCI30542
- 11. Weber SN, Wasmuth HE. Liver fibrosis: from animal models to mapping of human risk variants. Best Pract Res Clin Gastroenterol. 2010;24(5):635–646. DOI: 10.1016/j.bpg.2010.07.013.
- 12. Natarajan SK, Thomas S, Ramamoorthy P, Basivireddy J, Pulimood AB, Ramachandran A et al. Oxidative stres in the development of liver cirrhosis: a comparison of two different experimental models. J Gastroenterol Hepatol. 2006; 21(6):947–957. DOI: 10.1111/j.1440-1746.2006.04231.x
- 13. Jang JH, Kang KJ, Kim YH, Lee IS. Reevaluation of experimentalmodel of hepatic fibrosis induced by hepatotoxic drugs: an easy, applicable, and reproducible model. Transplant Proc. 2008;40(8):2700–2703. DOI: 10.1016/j.transproceed.2008.07.040 14. Placios SR, Roderfeld M, Hemmann S, Rath T, Atanasova S, Tschuschner A et al. Activation of hepatic stellate cells is associated with cytokine expression inthioacetamide-induced hepatic fibrosis in mice. Lab Invest. 2008;88(11):1192–1203. DOI: 10.1038/labinvest.2008.91
- 15. Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med. 2000; 21(3):49–98. DOI: 10.1016/s0098-2997(00)00004-2
- 16. Cheong JY, Kim DJ, Hwang SG, Yang JM, Kim YB, Park YN et al. Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels. Liver Int. 2011;31(9):1352–1358. DOI: 10.1111/j.1478-3231.2011.02570.x
Determination of effects of chemical agencies on liver fibrosis models frequently used in different dose and time periots
Abstract
Aim: In this study, it was aimed to reveal a more effective model depending on the dose and time by evaluating histopathological properties and biochemical parameters, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, triglyceride, cholesterol in carbon tetrachloride and thioacetamide (CCl4 and
TAA) models.
Method: Rats were divided into three groups for each model and intraperitoneally (i.p.) injected with CCl4 (0.5 ml/kg, 1.0 ml/kg, 2.0 ml/kg) and TAA (100 mg/kg, 200 mg/ kg, 300 mg/kg) for 4, 6 and 8 weeks, three times weekly, respectively.
Results: In the biochemical investigation, ALT and AST values in the only 0,5 ml CCL4 of groups for 6 and 8 weeks and were found to have significant differences compared to the control groups (p <0.05), while the other biochemicals parameters values did not reveal significant difference in the groups (p >0.05). According to the
results of the histopathology in the liver tissues, both the control groups showed a normal histological feature. The hepatofibrotic alterations were remarkable in the CCl4 and TAA models fibrosis depending on the increasing dose and time in all of the groups.
Conclusion: Our results showed that the dose and time were reached up to until the cirrhosis for eighth week. These results would be a helpful reference for hepatofibrotic studies.
Project Number
TSA-2016-6571
References
- 1. Anthony PP, Ishak KG, Nayak NC, Poulsen HE, Scheuer PJ, Sobin LH. The morphology of cirrhosis: definition, nomenclature, and classification. Bull World Health Organ 1977;55(4):521–540. PMID 304393
- 2. Koh C, Heller T. Approach to the diagnosis of portal hypertension. Theo Heller. 2012;1(5): 133-135. DOI: 10.1002/cld.00078
- 3. Floreanı A, Cazzagon N, Martines D, Cavalletto L, Baldo V, Chemello L. Performance and utility of transient elastography and noninvasive markers of liver fibrosis in primary biliary cirrhosis. Dig Liver Dis. 2011;43(11):887-892. DOI: 10.1016/j.dld.2011.06.011
- 4. Poupon R, Corpechot C. Elastography-based assessment of primary biliary cirrhosis staging. Dig Liver Dis. 2011;3(11):839-840. DOI: 10.1016/j.dld.2011.08.001
- 5. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. Annu Rev Pathol. 2011; 6:425–456. DOI: 10.1146/annurev-pathol-011110-130246
- 6. Popov Y, Schuppan D. Targeting liver fibrosis: strategies for development and validation of antifibrotic therapies. Hepatology. 2009;50(4):1294–1306. DOI: 10.1002/hep.23123
- 7. Park HJ, Kim HG, Wang JH, Choi MK, Han JM, Lee JS, Son CG. Comparison of TGF-b, PDGF, and CTGF in hepatic fibrosis models using DMN, CCl4, and TAA. Drug Chem Toxicol. 2016;39(1):111–118. DOI: 10.3109/01480545.2015.1052143
- 8. Fortea JI, Fernández-Mena C, Puerto M, Ripoll C, Almagro J, Bañares J, et al. Comparison of two protocols of carbon tetrachloride-induced cirrhosis in rats - improving yield and reproducibility. Sci Rep 2018;8:1–10. DOI:10.1038/s41598-018-27427-9
- 9. Akhtar T, Sheikh N. An overview of thioacetamide-induced hepatotoxicity. Toxin Rev 2013;32:43–46 DOI: 10.3109/15569543.2013.805144
- 10. Iredale JP. Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest. 2007;117(3):539–548. DOI: 10.1172/JCI30542
- 11. Weber SN, Wasmuth HE. Liver fibrosis: from animal models to mapping of human risk variants. Best Pract Res Clin Gastroenterol. 2010;24(5):635–646. DOI: 10.1016/j.bpg.2010.07.013.
- 12. Natarajan SK, Thomas S, Ramamoorthy P, Basivireddy J, Pulimood AB, Ramachandran A et al. Oxidative stres in the development of liver cirrhosis: a comparison of two different experimental models. J Gastroenterol Hepatol. 2006; 21(6):947–957. DOI: 10.1111/j.1440-1746.2006.04231.x
- 13. Jang JH, Kang KJ, Kim YH, Lee IS. Reevaluation of experimentalmodel of hepatic fibrosis induced by hepatotoxic drugs: an easy, applicable, and reproducible model. Transplant Proc. 2008;40(8):2700–2703. DOI: 10.1016/j.transproceed.2008.07.040 14. Placios SR, Roderfeld M, Hemmann S, Rath T, Atanasova S, Tschuschner A et al. Activation of hepatic stellate cells is associated with cytokine expression inthioacetamide-induced hepatic fibrosis in mice. Lab Invest. 2008;88(11):1192–1203. DOI: 10.1038/labinvest.2008.91
- 15. Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med. 2000; 21(3):49–98. DOI: 10.1016/s0098-2997(00)00004-2
- 16. Cheong JY, Kim DJ, Hwang SG, Yang JM, Kim YB, Park YN et al. Serum markers for necroinflammatory activity in patients with chronic viral hepatitis and normal or mildly elevated aminotransferase levels. Liver Int. 2011;31(9):1352–1358. DOI: 10.1111/j.1478-3231.2011.02570.x
Details
| Primary Language | English |
|---|---|
| Subjects | Surgery |
| Journal Section | Research Article |
| Authors | |
| Project Number | TSA-2016-6571 |
| Publication Date | April 23, 2021 |
| Submission Date | July 30, 2020 |
| Acceptance Date | November 27, 2020 |
| Published in Issue | Year 2021 Volume: 5 Issue: 1 |
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