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2018, vol. 69, iss. 1, pp. 38-44
Quantification of thioacetamide-induced liver necrosis using fractal analysis
aUniversity of Belgrade, Faculty of Medicine
bUniversity of Belgrade, Faculty of Medicine, Institute of Histology and Embryology
Keywords: hepatic encephalopathy; toxicity; liver lobule; box-counting
Introduction: The liver is particularly susceptible to the toxicity from numerous chemical agents, because of its central role in the detoxification. Thioacetamide-induced liver injury is used as an animal model of acute hepatic failure. Fractal analysis is a mathematical method used to measure the complexity of natural objects and can be represented solely using one parameter - the fractal dimension. Aim: The aim of this study was to investigate whether fractal analysis could be used to determine and quantify the hepatotoxic effect of thioacetamide on rat liver. Material and methods: Adult male Wistar rats were randomized into two groups: experimental group undergoing treatment with thioacetamide (600 mg/kg i.p.) and control group undergoing treatment with saline. Tissue samples were stained with hematoxylin & eosin (H&E) and Masson's trichrome protocol. Graphic processing and fractal analysis were performed using the ImageJ software. Two fractal dimensions were calculated: the fractal dimension of liver parenchyma (Dpar) and the fractal dimension of liver sinusoids (Dsin). Results: Dpar value was significantly lower in the experimental group, as compared to the control, both samples stained with H&E and Masson's trichrome (p < 0.0001). Dsin value was significantly higher in the experimental group, in tissue samples stained with H/E (p < 0.0001). Additionally, we calculated the Dpar/Dsin ratio, which was significantly lower in the experimental group, in tissue samples stained with both H&E and Masson's trichrome protocol. Conclusion: These results show that fractal analysis could prove as a useful, easy and low-cost method in the detection and quantification of thioacetamide-induced liver necrosis.
Avraham, Y., Grigoriadis, N., Poutahidis, T., Vorobiev, L., Magen, I., Ilan, Y., Mechoulam, R., Berry, E. (2011) Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice. British Journal of Pharmacology, 162(7): 1650-1658
Bianciardi, G., Borruso, L. (2015) Nonlinear analysis of random walks: a tool to analyze nucleic acid sequences. Fractal Geometry and Nonlinear Analysis in Medicine and Biology, 1(1):
Cross, S.S. (1997) Fractals in pathology. Journal of Pathology, 182(1): 1-8
de Arruda, P.F.F., Gatti, M., Junior, F.N.F., de Arruda, J.G.F., Moreira, R.D., Murta, L.O., de Arruda, L.F., de Godoy, M.F. (2013) Quantification of fractal dimension and Shannon’s entropy in histological diagnosis of prostate cancer. BMC Clinical Pathology, 13(1):
de David, C., Rodrigues, G., Bona, S., Meurer, L., González-Gallego, J., Tuñón, M.J., Marroni, N.P. (2011) Role of Quercetin in Preventing Thioacetamide-Induced Liver Injury in Rats. Toxicologic Pathology, 39(6): 949-957
Devarbhavi, H. (2012) An Update on Drug-induced Liver Injury. Journal of Clinical and Experimental Hepatology, 2(3): 247-259
di Ieva, A., Grizzi, F., Jelinek, H., Pellionisz, A.J., Losa, G.A. (2014) Fractals in the Neurosciences, Part I: General Principles and Basic Neurosciences. Neuroscientist, 20(4): 403-417
Dioguardi, N. (2006) Liver fibrosis and tissue architectural change measurement using fractal-rectified metrics and Hurst’s exponent. World Journal of Gastroenterology, 12(14): 2187
Fabrizii, M., Moinfar, F., Jelinek, H.F., Karperien, A., Ahammer, H. (2014) Fractal Analysis of Cervical Intraepithelial Neoplasia. PLoS one, 9(10): e108457
Falconer, K. (2005) Fractal Geometry. Chichester, UK: Wiley
Gaudio, E., Chaberek, S., Montella, A., Pannarale, L., Morini, S., Novelli, G., Borghese, F., Conte, D., Ostrowski, K. (2005) Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver. Journal of Anatomy, 207(2): 107-115
Hassan, H., Serag, H., Abdel-Hamid, N., Amr, M. (2015) Synergistic curative effect of chicory extract and cisplatin against thioacetamide-induced hepatocellular carcinoma. Hepatoma Research, 1(3): 147
Lee, W.M., Squires, R.H., Nyberg, S.L., Doo, E., Hoofnagle, J.H. (2007) Acute liver failure: Summary of a workshop. Hepatology, 47(4): 1401-1415
Leise, M.D., Poterucha, J.J., Talwalkar, J.A. (2014) Drug-Induced Liver Injury. Mayo Clinic Proceedings, 89(1): 95-106
Lim, S., Lee, S., Nam, K., Kim, K.H., Mar, W. (2013) Hepatoprotective effects of reynosin against thioacetamide-induced apoptosis in primary hepatocytes and mouse liver. Archives of Pharmacal Research, 36(4): 485-494
Losa, G.A. (2012) Fractals and their contribution to biology and medicine. Medicographia, 34: 365-74
Losa, G.A., Ristanović, D., Ristanović, D., Zaletel, I., Beltraminelli, S. (2016) From Fractal Geometry to Fractal Analysis. Applied Mathematics, 07(04): 346-354
Luo, M., Dong, L., Li, J., Wang, Y., Shang, B. (2015) Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats. Int J Clin Exp Pathol, 8(8); 8990-6
Mandelbrot, B.B. (1982) The fractal geometry of nature. San Francisco: W.H. Freeman and Co Ltd, 460 p, Updated and Augmented edition
Milošević, N.T., Ristanović, D., Jelinek, H.F., Rajković, K. (2009) Quantitative analysis of dendritic morphology of the alpha and delta retinal ganglion cells in the rat: A cell classification study. Journal of Theoretical Biology, 259(1): 142-150
Miranda,, Rodrigues, D.H., Vieira, L.B., Lima, C.X., Rachid, M.A., Vidigal, P.V.T., Gomez, M.V., Reis, H.J.D., Guatimosim, C., Teixeira, A.L. (2010) A thioacetamide-induced hepatic encephalopathy model in C57BL/6 mice: A behavioral and neurochemical study. Arquivos de neuro-psiquiatria, 68(4): 597-602
Mladenović, D., Hrnčić, D., Rašić-Marković, A., Puškaš, N., Petrovich, S., Stanojlović, O. (2013) Spectral analysis of thioacetamide-induced electroencephalographic changes in rats. Human & Experimental Toxicology, 32(1): 90-100
Mladenović, D., Krstić, D., Colović, M., Radosavljević, T., Rasić-Marković, A., Hrncić, D., Macut, D., Stanojlović, O. (2012) Different sensitivity of various brain structures to thioacetamide-induced lipid peroxidation. Medicinal chemistry, 8(1): 52-8
Mladenović, D., Hrnčić, D., Petronijević, N., Jevtić, G., Radosavljević, T., Rašić-Marković, A., Puškaš, N., Maksić, N., Stanojlović, O. (2014) Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy. American Journal of Physiology-Gastrointestinal and Liver Physiology, 307(9): G931-G940
Mladenović, D., Radosavljević, T., Hrnčić, D., Rašić-Marković, A., Puškaš, N., Maksić, N., Djuric, D., Stanojlović, O. (2012) Behavioral and electroencephalographic manifestations of thioacetamide-induced encephalopathy in rats. Canadian Journal of Physiology and Pharmacology, 90(9): 1219-1227
Mladenović, D., Petronijević, N., Stojković, T., Velimirović, M., Jevtić, G., Hrnčić, D., Radosavljević, T., Rašić-Marković, A., Maksić, N., Djuric, D., Stanojlović, O. (2015) Finasteride Has Regionally Different Effects on Brain Oxidative Stress and Acetylcholinesterase Activity in Acute Thioacetamide-Induced Hepatic Encephalopathy in Rats. PLOS one, 10(8): e0134434
Moal, F. (2002) Fractal dimension can distinguish models and pharmacologic changes in liver fibrosis in rats. Hepatology, 36(4): 840-849
Panackel, C., Thomas, R., Sebastian, B., Mathai, S. (2015) Recent advances in management of acute liver failure. Indian Journal of Critical Care Medicine, 19(1): 27
Pantic, I., Nesic, Z., Paunovic, P.J., Radojević-Škodrić, S., Cetkovic, M., Basta, J.G. (2016) Fractal analysis and Gray level co-occurrence matrix method for evaluation of reperfusion injury in kidney medulla. Journal of Theoretical Biology, 397: 61-67
Pantic, I., Paunovic, J., Basta-Jovanovic, G., Perovic, M., Pantic, S., Milosevic, N.T. (2013) Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice. Experimental Gerontology, 48(9): 926-932
Pantic, I., Petrovic, D., Paunovic, J., Vucevic, D., Radosavljevic, T., Pantic, S. (2016) Age-related reduction of chromatin fractal dimension in toluidine blue - stained hepatocytes. Mechanisms of Ageing and Development, 157: 30-34
Porter, W.R., Neal, R.A. (1978) Metabolism of thioacetamide and thioacetamide S-oxide by rat liver microsomes. Drug Metab Dispos, Aug; 6(4); 379-88
Puškaš, N., Zaletel, I., Stefanović, B.D., Ristanović, D. (2015) Fractal dimension of apical dendritic arborization differs in the superficial and the deep pyramidal neurons of the rat cerebral neocortex. Neuroscience Letters, 589: 88-91
Rahman, T.M., Hodgson, H.J.F. (2000) Animal models of acute hepatic failure. Int J Exp Pathol, Apr; 81(2); 145-57
Saleh, D.O., Abdel, J.G.A., El-Awdan, S.A., Oraby, F., Badawi, M. (2014) Thioacetamide-induced liver injury: protective role of genistein. Canadian Journal of Physiology and Pharmacology, 92(11): 965-973
Shawcross, D., Jalan, R. (2005) The pathophysiologic basis of hepatic encephalopathy: central role for ammonia and inflammation. Cellular and Molecular Life Sciences, 62(19-20): 2295-2304
Smith, T.G., Lange, G.D., Marks, W.B. (1996) Fractal methods and results in cellular morphology: Dimensions, lacunarity and multifractals. J Neurosci Methods, 69(2): 123-36
Stankovic, M., Pantic, I., de Luka, S.R., Puskas, N., Zaletel, I., Milutinovic-Smiljanic, S., Pantic, S., Trbovich, A.M. (2015) Quantification of structural changes in acute inflammation by fractal dimension, angular second moment and correlation. Journal of Microscopy, 261(3): 277-284
Streba, C.T., Pirici, D., Vere, C.C., Mogoantă, L., Comănescu, V., Rogoveanu, I. (2011) Fractal analysis differentiation of nuclear and vascular patterns in hepatocellular carcinomas and hepatic metastasis. Rom J Morphol Embryol, 52(3):845-54
Tambasco, M., Costello, B.M., Kouznetsov, A., Yau, A., Magliocco, A.M. (2009) Quantifying the architectural complexity of microscopic images of histology specimens. Micron, 40(4): 486-494
Zaletel, I., Ristanović, D., Stefanović, B.D., Puškaš, N. (2015) Modified Richardson's method versus the box-counting method in neuroscience. Journal of Neuroscience Methods, 242: 93-96


article language: English
document type: Original Scientific Paper
DOI: 10.5937/mp69-12623
published in SCIndeks: 26/04/2018
peer review method: double-blind
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