Proliferating Cell Nuclear Antigen as A Biomarker for Thioacetamide Induced Hepatotoxicity of Rat Liver

Ehab Tousson^1, , Ehab M.M. Ali², ADbdel Halim A. Moustafa³, Said S. Moselhey³ and Karim S. El-Said²

¹Department of Zoology, Faculty of Science, Tanta University, Egypt

²Department of Chemistry; Faculty of Science, Tanta University, Egypt

³Department of Biochemistry, Faculty of Science, Ain Shams University, Egypt

Cite this paper:
Ehab Tousson, Ehab M.M. Ali, ADbdel Halim A. Moustafa, Said S. Moselhey and Karim S. El-Said. Proliferating Cell Nuclear Antigen as A Biomarker for Thioacetamide Induced Hepatotoxicity of Rat Liver. American Journal of Zoological Research. 2014; 2(3):51-54. doi: 10.12691/ajzr-2-3-3

Abstract

Thioacetamide (TAA) is a potent hepatotoxin that causes centrilobulal necrosis and nephrotoxic damage following acute administration. Prolonged exposure to TAA can result in bile duct proliferation and liver cirrhosis histologically similar to that caused due to viral hepatitis infection. Hepatic cirrhosis is a complex disease in which several biological, biochemical and chemical alterations are combined, none of these alone being sufficient for diagnosis. The morphological characteristics of the final stages of cirrhosis are well known, but the initial lesions and intermediate stages still have not been fully clarified. Therefore, this work aimed to use of Proliferating cell nuclear antigen (PCNA) immunohistochemistry as a marker to differentiate between the control liver and hepatotoxicity by thioacetamide intoxicated group in the male rats. Eight rats were equally divided into 2 groups; the first group was the control group and the second group was injected with TAA by 200 mg/kg body weight twice a week for 12 week. Our results showed that the liver of normal control rats negatively react with PCNA-ir, and the liver sections of the rats intoxicated with TAA showed strong positive reaction for PCNA. Further, we recommend the PCNA index a useful marker for hepatotoxicity.

Keywords:
hepatotoxicity thioacetamide immunohistochemistry PCNA Rats

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Friedman S. Liver fibrosis from bench to bedside. J. Hepatol 2003; 38: 38-53.
[2]	Pinzani M, Rombouts K. Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 2004; 36: 231-242
[3]	Sakeran M.I, Zidan N, Rehman H, Aziz AT, Saggu S. Abrogation by Trifolium alexandrinum root extract on hepatotoxicity induced by acetaminophen in rats. Redox Rep 2014; 19 (1): 26-33.
[4]	Saggu S, Sakeran MI, Zidan N, Tousson E, Mohan AF, Rehman H. Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats. Food and Chemical Toxicology 2014; 72; 138-146.
[5]	Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004; 39: 273-278.
[6]	Ramadori G, Saile B. Inflammation, damage repair, immune cells, and liver fibrosis: specific or nonspecific, this is the question. Gastroenterology 2004; 127: 997-1000.
[7]	Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med 2000; 21: 49-98.
[8]	Chieli E, Malvaldi G. Role of the microsomal FAD-containing monooxygenase in the liver toxicity of thioacetamide S-oxide. Toxicology 1984; 31: 41-51.
[9]	Torres MI, Fernandez MI, Gil A, Rios A. Dietary nucleotides have cytoprotective properties in rat liver damaged by thioacetamide. Life Sci 1998; 62: 13-22.
[10]	Ledda-Columbano GM, Coni P, Curto M, Giacomoni L, Faa G, Oliverio S, et al. Induction of two different modes of cell death, apoptosis and necrosis, in rat liver after a single dose of thioacetamide. Am J Pathol 1991; 139 (5): 1099-1109.
[11]	Bruck R, Aeed H, Schey R, Matas Z, Raifen R, Zaiger G, Hochman A, Avni Y. Pyrrolidine dithiocarbamate protects against thioacetamide-induced fulminant hepatic failure in rats. J Hepatol 2002; 36: 370-377.
[12]	Edmund CS, Wong Kar-lok H, Tian-chyuan T, Sheng-chou L, Chi-feng. Tetramethylpyrazine protects mice against thioacetamide-induced acute hepatotoxicity. J Biomed Sci 2002; 9: 410-414.
[13]	Bruck R, Aeed H, Avni Y, Shirin H, Matas Z, Shahmurov M, Avinoach I, Zozulya G, Weizman N, Hochman A. Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats. J Hepatol 2004; 40: 86-93.
[14]	Shapiro H, Ashkenazi M, Weizman N, Shahmurov M, Aeed H, Bruck R. Curcumin ameliorates acute thioacetamide-induced hepatotoxicity. J Gastroenterol Hepatol. 2006; 21 (2): 358-66.
[15]	Waseem NH, Labib K, Nurse P, Lane DP. Isolation and analysis of the fission yeast gene encoding polymerase delta accessory protein PCNA. EMBO J 1992; 11 (13): 5111-5120.
[16]	Madsen P, Celis JE. S-Phase patterns of cyclin (PCNA) antigen staining resemble topographical patterns of DNA synthesis. FEBS Lett 1995; 193 (1): 5-11.
[17]	Zhang H, Xiong Y, Beach D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell 1993; 4 (9): 897 906.
[18]	Tousson E, Hafez E, Masoud A, Hassan AA. Abrogation by curcumin on testicular toxicity induced by Cisplatin in rats. Journal of Cancer Research and Treatment, 2014, 2 (3): 64-68.
[19]	Hindges R, Hubscher U. DNA polymerase delta, an essential enzyme for DNA transactions. Biol Chem 1997; 378 (5): 345-362.
[20]	Shivji MK, Kenny M, Wood RD. Proliferating cell nuclear antigen is required for DNA excision repair. Cell 1992; 69 (2): 367-374.
[21]	Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox S. Characterisation of the interaction between PCNA and Gadd45. Oncogene 1995; 10: 2427-2433.
[22]	Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor for cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994; 369: 574-578.
[23]	Zeng L, Kong XT, Su JW, Xia TL, Na YQ, Guo YL. Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index. Asian J Androl 2001; 3 (1): 63-66.
[24]	Bancroft JD, Stevens A. Theory and Practice of Histological Technique. 3rd Ed. Churchill Livingstone. Edinburgh, London. 1990.
[25]	Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharm 2007; 109: 214-218.
[26]	Linden MD, Torres FX, kubus J, Zarbo RJ. Clinical application of morphologic and immunocytochemical assessments of cell proliferation. Am J Clin Pathol 1992; 97 [Suppl]: S4-S13.
[27]	Kurki P, Ogata K, Tan EM. Monoclonal antibodies to proliferating cell nuclear antigen (PCNA)/cyclin as probes for proliferating cells by immunofluorescence microscopy and flow cytometry. J Immunol Methods 1988; 109: 49-59.
[28]	Bravo R, Frank R, Blundell PA, Macdonald-Bravo H. Cyclin/PCNA is the auxillary protein DNA polymerase delta. Nature 1987; 26: 515-517.
[29]	Celis JE, Celis A. Cell cycle dependent variations in the distribution of the nuclear protein cyclin/proliferating cell nuclear antigen in cultured cells: sub-division of S phase. Proc Natl Acad Sci USA 1982; 82: 3262-3266.
[30]	Van Dierendonck JH, Wijsman JH, Keijzer R, van de Velde C, Corneliss C. Cell-cycle-related staining patterns of anti-proliferating cell nuclear antigen monoclonal antibodies. Comparison with BrdU labeling and Ki67 staining. Am J Pathol 1991; 138: 1165-1172.
[31]	Sakr S, ElKenawy A, El-Sahara D. Protective effect of licorice on metiram fungicide induced liver injury in mice. Canadian J Pure Appl Sci 2009; 3: 787-93.