Alteration in Antioxidant Defense System and Oxidative Stress in blood for Non Alcoholic Fatty Liver Disease

A.P. Thakkar¹ , H.J. Shah² , N.D. Patel³ , J.G. Shah⁴

1. Dept. of Biochemistry, M. B. Patel Science College (Affiliated to Sardar Patel University), Anand, India.
2. Dept. of Biochemistry, M. B. Patel Science College (Affiliated to Sardar Patel University), Anand, India.
3. Jiwandeep Hospital, Anand, India.
4. National Dairy Development Board (NDDB), Anand, India.

Correspondence should be addressed to: hjsapt@gmail.com.

Section:Research Paper, Product Type: Isroset-Journal
Vol.4 , Issue.5 , pp.1-10, Oct-2017

CrossRef-DOI:   https://doi.org/10.26438/ijsrbs/v4i5.110

Online published on Oct 30, 2017

Copyright © A.P. Thakkar, H.J. Shah, N.D. Patel, J.G. Shah . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

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Abstract :
Antioxidants neutralize free radicals or reactive oxygen species which cause oxidative stress. Oxidative stress is a major contributor in the pathogenesis of Non-alcoholic fatty liver disease (NAFLD). Present study is aimed to know level of antioxidant defense system and oxidative stress in controls and NAFLD participants. The cross-sectional study was carried out at tertiary centre of gastroenterologist unit at Anand. Experimental participants were divided into two groups: Control (n= 52, Age- 26.7±1.23 years, 39 M/ 13 F) and NAFLD (n= 48, Age- 41.71±1.71, 43 M/5 F). All participants underwent anthropometric assessment, clinical examination, biochemical parameters, antioxidant parameters and lipid peroxidation marker or oxidative stress marker (MDA- Malondialdehyde). Results of our study indicate significant increase in markers of metabolic syndrome (obesity, dyslipidaemia) and liver enzymes in NAFLD compared to controls. Total antioxidant activity (Gallic acid equivalent (GAE (p=0.0008)) and Trolox equivalent (TE (p<0.0001)) and antioxidant enzymes such as superoxide dismutase (SOD (p=0.0023)), Glutathione Peroxidase (GSHPx (p<0.0001)), Glutathione-s-transferase (GST (p<0.0001)) and Catalase (CAT (p<0.0001)) were significantly decreased in NAFLD compared to controls. Lipid peroxidation marker or oxidative stress marker (MDA) was significantly increased (p<0.0001) in NAFLD compared to controls. Our study concludes that NAFLD participants have increased oxidative stress and decreased antioxidant levels compared to controls. Study strongly indicates that antioxidant enzymes namely GST and CAT can be used as surrogate markers of oxidative stress for NAFLD participants.

Key-Words / Index Term :
Anthropometric Assessment; Biochemical Parameters; Oxidative Stress Marker; Total Antioxidant Activity; Antioxidant Enzymes

References :
[1]. S. McPherson, T. Hardy, E. Henderson, A.D. Burt, C.P. Day, Q.M. Anstee. “Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: Implications for prognosis and clinical management”, Journal of Hepatology, Vol. 62, pp. 1148–1155, 2015.
[2]. C.D. Byrne, G. Targher. “NAFLD: A multisystem disease”, Journal of Hepatology, Vol. 62, pp. S47–S64, 2015.
[3]. S.F. Assimakopoulos, C. Gogos, C. Labropoulou-Karatza. “Could antioxidants be the "magic pill" for cirrhosis-related complications? A pathophysiological appraisal”. Med Hypotheses, Vol. 77, Issue 3, pp. 419-423, 2011.
[4]. A. Duseja, “Non-alcoholic fatty liver disease in India – a lot done yet more required!” Indian J Gastroenterol, Vol. 29, pp.217–225, 2010.
[5]. L.A. Adams, P. Angulo, K. Lindor, “Non-alcoholic fatty liver disease”. CMAJ, Vol. 29, Issue 172 (7), pp. 899-905, 2005.
[6]. E. Fitzpatrick, A. Dhawan, “Noninvasive biomarkers in non-alcoholic fatty liver disease: current status and a glimpse of the future”. World J Gastroenterol, Vol. 21, Issue 20(31), pp.10851-10863, 2014.
[7]. D. Preiss, N. Sattar, “Non-alcoholic fatty liver disease: an overview of prevalence diagnosis pathogenesis and treatment considerations”. Clinical Science, Vol. 115, pp. 141–150, 2008.
[8]. P. Angulo, “Obesity and Nonalcoholic Fatty Liver Disease”, Nutrition Reviews, Vol. 65, Issue 6, pp. S57–S63, 2007.
[9]. P. Paschos, K Paletas, “Non-alcoholic fatty liver disease and metabolic syndrome”, Hippokratia, Vol. 13, Issue 1, pp. 9-19, 2009.
[10]. J.K. Dowman, J. W. Tomlinson, P. N. Newsome, “Pathogenesis of non-alcoholic fatty liver disease”, Q J Med, Issue 103, pp. 71–83, 2010.
[11]. B. Yilmaz, K. Sahin, H. Bilen, I.H. Bahcecioglu, B. Bilir, S. Ashraf, K.J. Halazun, O. Kucuk, et al. “Carotenoids and non-alcoholic fatty liver disease”, HepatoBiliary Surg Nutr, Vol. 4, Issue 3, pp. 161-171, 2015.
[12]. A.A. Salgado, L.D. Carvalho, A.C. Oliveira, V.N. Santos, J.G. Vieira, E.R. Parise, “Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals”, Arq Gastroenterol, Vol. 47, Issue 2, pp. 165-169, 2010.
[13]. Sha Li, Hor-Yue Tan, NingWang, Zhang-Jin Zhang, Lixing Lao, Chi-WoonWong, Yibin Feng, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int. J. Mol. Sci. 2015; 16: 26087–26124.
[14]. G.C. Farrell, C.Z. Larter, “Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis”, Hepatology, Vol. 43, pp. S99-S112, 2006.
[15]. M. Percival, Antioxidants, Clinical Nutrition Insights, pp. 1-4.
[16]. N. Sapojnikova, N. Asatiani, T. Kartvelishvili, I. Kalandadze, A. Tsiskaridze, “Plasma antioxidant activity as a marker for a favorable outcome in acute ischemic stroke”, Antioxidant Enzyme, pp. 142-168, 2012.
[17]. M.M. Al-Shahrani, G.S. Zaman, M. Amanullah, “Measurement of antioxidant activity in selected food products and neutraceuticals”, J. Nutr Food Sci., Vol. 3, Issue 3, pp. 1-6, 2013.
[18]. M. Koruk, S. Taysi, M.C. Savas, O. Yilmaz, F. Akcay, M. Karakok, “Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis”. Annals of Clinical & Laboratory Science, Vol. 34, Issue 1, pp. 57-62, 2004.
[19]. E.A. Nantia, F.P. Manfo, N.S. Beboy, P.F. Moundipa. “In vitro antioxidant activity of the methanol extract of Basella alba L (Basellaceae) in rat testicular homogenate”. Oxidant Antioxidant Med Sci., Vol. 2, Issue 2, pp.131-136, 2013.
[20]. K.P. Jaiswal, A. Sarsavan, R.K. Chaudhary, S.A. Ali, M.K. Tembre, “The etiological features and treatment of vitiligo : A pilot study prospective to Indian scenario”, International Journal of Scientific Research in Biological Science, Vol-1, Issue-1, pp.10-17, 2014.
[21]. I.A. Leclercq, “Antioxidant defence mechanisms: new players in the pathogenesis of non-alcoholic steatohepatitis?, Clinical Science, Vol. 106, pp. 235–237, 2004.
[22]. N.A. Ismail, S.H. Okasha, A. Dhawan, A.M. Abdel Rahman, N.A. Hamid, O. Shaker, “Glutathione peroxidase superoxide dismutase and catalase activities in children with chronic hepatitis”. Advances in Bioscience and Biotechnology, Vol. 3, pp. 972-977, 2012.
[23]. G. Shiota, H. Tsuchiya. “Pathophysiology of NASH: Insulin resistant free fatty acids and oxidative stress”, J. Clin. Biochem. Nutr, Vol. 38, pp. 127-132, 2006.
[24]. C.P. Oliveira, A.M. Coelho, H.V. Barbeiro, V.M. Lima, F. Soriano, C. Ribeiro, N.A. Molan, V.A. Alves, H.P. Souza, M.C. Machado, F.J. Carrilho, “Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease”, Braz J. Med. Biol. Res. Vol. 39, Issue 2, pp. 189-194, 2006.
[25]. Wen-Ce Zhou, Quan-Bao Zhang, Liang Qiao. Pathogenesis of liver cirrhosis, World J Gastroenterol, Vol. 21, Issue 20(23), pp. 7312-7324, 2014.
[26]. I. Shimizu, N. Shimamoto, K. Saiki, M. Furujo, K. Osawa. “Lipid peroxidation in hepatic fibrosis. In tech open science/open minds”, Kanagawa: Japan, pp. 483-492, 2012.
[27]. O. Pirgon, H. Bilgin, F. Cekmez, H. Kurku, B.N. Dundar, “Association between Insulin resistant and oxidative stress parameters in obese adolescents with non alcoholic fatty liver disease”, J. Clin Res Pediatr Endocrinol; Vol. 5, Issue 1, pp. 33-39,2013.
[28]. R. Kumar, S. Prakash, S. Chhabra, V. Singla, K. Madan, D. Gupta, S.K. Panda, S. Kanal and S.K. Acharya, “Association of pro-inflammatory cytokines, adipokines and oxidative stress with insulin resistant and non alcoholic fatty liver disease”, Indian J Med Res; Vol. 136, pp. 229-36, 2012.
[29]. Z. Yesilova, H. Yaman., C. Oktenli, A. Ozcan, A. Uygun, E. Cakir, S.Y. Sanisoglu, A. Erdil , Y. Ates, M. Aslan, U. Musabak, M.K. Erbil, N. Karaeren and K. Dagalp, “Systemic Markers of Lipid Peroxidation and Antioxidants in Patients with Nonalcoholic Fatty Liver Disease”, The American Jr. of Gastroenterology, Vol. 100, pp. 850-855, 2005.
[30]. G. Baskol, M. Baskol and D. Kocer, “Oxidative stress and antioxidant defense in serum of pateints with non alcoholic steatohepatitis”, Clinical Biochemistry, Vol. 40, pp. 776-780, 2007.
[31]. E. Koroglu, B. Canbakan, K. Atay, I. Hatemi, M. Tuncer, A. Dobrucali, A. Sonsuz, I. Gultepe, H. Senturk, “Role of oxidative stress and insulin resistance in disease severity of non alcoholic fatty liver disease”, Turk J Gastroenterol, Vol. 27, pp. 361-366, 2016.
[32]. M. Notarnicola, V. Tutino, A.R. Osella, C. Bonfiglio, V. Guerra and M.G. Caruso, “Increased serum levels of oxidative stress markers in patients with liver steatosis”, J. Liver, Vol. 2, Issue 3, pp. 1000127.
[33]. S. Saluja, K. Arora. “Overweight and obesity and its association with blood pressure levels amongst females of Bathinda, Punjab”, India J. maternal child health physiological dept., Adesh institute of medical science ad research –Bathinda, Vol. 12, pp. 11- 13, 2010.
[34]. I.F. Benzie, J. J. Strains, “The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay”, Anal Biochem, Vol. 239, pp.70-76, 1996.
[35]. E. Beutler, “Red cell metabolism”, A Manual of Biochemical Methods, 3rd ed. Grune and Stratton Inc., New York, 1984.
[36]. D.E. Paglia, W.N. Valentine, “Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase”, J. Lab Clin. Med, Vol. 70, Issue 1, pp.158-169, 1967.
[37]. I. Carlbeg, B. Mannervik, J. Biol. Chem., Vol. 250, pp. 5475-5480, 1975.
[38]. H. Aebi, “Catalase in vitro methods”, Enzymol, Vol. 105, pp. 121-126, 1984.
[39]. K. Prabhu, P.G. Bhat, D.M. Vasudevan, “Can serum glutathione-s-transferase levels in carcinoma cervix be a predictor of radiation response?”, Indian Jr. of Clinical Biochemistry, Vol. 20, Issue 1, pp. 95-97, 2005.
[40]. K. Asha, H.P. Kedilaya, K. Poomima, M. Cariappa, M. Nandini. “Oxidant and antioxidant status in vegetarians and fish eaters”, Indian Journal of Clinical Biochemistry, Vol. 18, Issue 2, pp. 197-205, 2003.
[41]. G.K. Kanji, “100 statistical tests”, SAGE publication, 3rd edition, London, Thousand Oaks, New Delhi, pp. 5-8, 2006.
[42]. L. Pacifico, E. Bonci, G. Andreoli, S. Romaggioli, R. D. Miscio, C.V. Lombardo, C. Chiesa, “Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness insulin resistance and non-alcoholic fatty liver disease in children and adolescents”, Nutrition Metabolism & Cardiovascular Diseases, pp. 1-7, 2014.
[43]. A.H. Kani, S.M. Alavian, A. Esmaillzadeh, P. Adibi, L. Azadbakht, “Dietary quality indices and biochemical parameters among patients with non-alcoholic fatty liver disease (NAFLD)”, Hepatitis Monthly, Vol. 13, Issue 7, pp. 1-10, 2013.
[44]. S.L. Sharma, S.A. Chokshi, D. Desai, H. Mewada, A. Singh, “Non enzymatic antioxidants, malondialdehyde and total antioxidant activity as markers of oxidative stress in arthritis and rheumatoid arthritis” , NHL Journal Of Medical Sciences, Vol. 2, Issue 1,pp. 57-60, 2013.
[45]. Y. Kambayashi, N.T. Binh, H.W. Asakura, Y. Hibino, Y. Hitomi, H. Nakamura, K. Ogino, “Efficient assay for total antioxidant capacity in human plasma using a 96-well microplate”, J. Clin. Biochem. Nutr., Vol. 44, pp. 46–51, 2009.

[46]. L.S. Bir, S. Demir, S. Rota, M. Koseoglu, “Increased serum malondialdehyde levels in chronic stage of ischemic stroke”, Tohoku J. Exp. Med, Vol. 208, pp. 33-39, 2006.
[47]. Y. Guo, P. Li, Q. Guo, K. Shang, D. Yan, S. Du, Y. Lu, “Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review”, Tropical Journal of Pharmaceutical Research, Vol. 12, Issue 6, pp. 1097-1105, 2013.
[48]. G.J. Beckett, J.D. Hayes, “Glutathione S-Transferase: Biomedical Applications”, Advances in Clinical Chemistry, Vol. 30, pp. 281–380, 1993.
[49]. K.M. Surapaneni, M. Jainu, “Comparative effect of pioglitazone quercetin and hydroxy citric acid on the status of lipid peroxidation and antioxidants in experimental non-alcoholic steatohepatitis”, Journal of Physiology and Pharmacology, Vol. 65, Issue 1, pp. 67-74, 2014.
[50]. K. Madan, P. Bhardwaj, S. Thareja, S. Gupta, A. Saraya, “Oxidant stress and antioxidant status among patients with nonalcoholic fatty liver disease (NAFLD)”, Journal of Clinical Gastroenterology, Vol. 40, Issue 10, pp. 930-935, 2006.
[51]. M.A. Hassanien, S.A. Abou-El-Noeman, E. Aboueladab, “Oxidative stress antioxidant and leptin status in patients with non-alcoholic steatohepatitis”, European Journal of Academic Essays, Vol. 1, Issue 10, pp. 17-22, 2014.
[52]. D. Bonnefont-Rousselot, V. Ratziu, P. Giral, F. Charlotte, I. Beucler, T. Poynard, “Blood oxidative stress markers are unreliable markers of hepatic steatosis”, Alimentary Pharmacology & Therapeutics, Vol. 23, pp. 91-98, 2006.
[53]. K. Richter, T. Kietzmann, “Reactive oxygen species and fibrosis: further evidence of a significant liaison”, Cell Tissue Res., Vol. 365, pp. 591-605, 2016.
[54]. M. Ekstedt, H. Hagstrom, P. Nasr, M. Fredrikson, P. Stal, S. Kechagias, R. Hultcrantz, “Fibrosis stage is the strongest predictor for disease specific mortality in NAFLD after up to 33 years of follow-up”, Hepatology, pp. 1547-1554, 2015.