ISSN: 2375-3838
International Journal of Clinical Medicine Research  
Manuscript Information
 
 
Pentoxiffiline Prevents Oxidative Stress Mediated Acute Liver Injury in Carbon Tetrachloride Treated Mice
International Journal of Clinical Medicine Research
Vol.5 , No. 2, Publication Date: Apr. 10, 2018, Page: 20-26
645 Views Since April 10, 2018, 420 Downloads Since Apr. 10, 2018
 
 
Authors
 
[1]    

Bidhan Chandra Chakraborty, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.

[2]    

Debasree Bishnu, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.

[3]    

Suman Santra, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.

[4]    

Gopal Krishna Dhali, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.

[5]    

Abhijit Chowdhury, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India; Indian Institute of Liver and Digestive Sciences, Kolkata, India.

[6]    

Amal Santra, Centre for Liver Research, School of Digestive & Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India; Indian Institute of Liver and Digestive Sciences, Kolkata, India.

 
Abstract
 

Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor which have role in prevention of oxidative stress, inflammation and fibrosis which ultimately affect the liver. The major goal of the study was to evaluate the role of PTX on carbon tetrachloride (CCl4) induced acute liver injury model and its possible mechanisms in mice. Male C57BL/6 mice were divided into four groups: control, PTX, CCl4 and PTX+ CCl4 treated groups. Mice were administrated CCl4 together with or without PTX for a week and sacrificed 72 hour after the last injection of CCl4 and PTX. Histopathological evaluation was performed. The liver function test, indices of oxidative stress including NADPH oxidase (NOX) and cytochrome P450 2E1 (CYP2E1) enzyme activity, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels in liver tissues were measured. mRNA expression of different pro inflammatory cytokines and protein expression of nuclear factor-κB (NF-Kb) were checked. PTX significantly attenuated CCl4-induced liver injury histopathologically and improves the liver function. PTX also remarkably suppressed the secretions of pro-inflammatory cytokines and translocation of the p65 subunits of NF-κB to nucleus induced by CCl4. In addition PTX can also reduce the generation of oxidative stress by decreasing the enzyme activity of NOX, CYP2E1 and the levels of MDA and also by increasing the cellular anti-oxidant GSH and SOD. In conclusion, PTX ameliorated the effects of CCl4 induced acute liver injury in mice by inhib¬iting oxidative stress, expression of pro-inflammatory cytokines and NF-κB activation.


Keywords
 

Acute Liver Injury, Oxidative Stress, Pentoxifilline


Reference
 
[01]    

Koblihova E, Lukšan O, Mrázova I, Ryska M, Cervenka L. Hepatocyte transplantation atten¬uates the course of acute liver failure induced by thioacetamide in Lewis rats. Physiol Res 2015; PMID: 25804092.

[02]    

Muriel P. Cytokines in liver diseases. In: Sahu S, editior. Hepatotoxicity: from genomics to in vitro and in vivo models. West Sussex, UK: John Wiley and Sons LTD; 2008. pp. 371-390.

[03]    

Koen YM, Sarma D, Hajovsky H, Galeva NA, Williams TD, Staudinger JL, Hanzlik RP. Protein targets of thioacetamide metabolites in rat he¬patocytes. Chem Res Toxicol 2013; 26: 564-574.

[04]    

Novobrantseva TI, Majeau GR, Amatucci A, et al. Attenuated liver fibrosis in the absence of B cells. J Clin Invest 2005; 115: 3072-3082.

[05]    

Czaja M J. Another Way for NADPH Oxidase to Send a Signal for Liver Injury. Gastroenterology. 2010; 129-6.

[06]    

Sun S, Zhang H, Xue B, Wu Y, Wang J, Yin Z, Luo L. Protective effect of glutathione against lipo¬polysaccharide-induced inflammation and mortality in rats. Inflamm Res 2006; 55: 504-510.

[07]    

Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterology 2014; 20: 8082.

[08]    

Hernandez-Flores G, Ortiz-Lazareno PC, Lerma-Diaz JM, Dominguez-Rodriguez JR, Jave-Suarez LF, Aguilar-Lemarroy Adel C, de Celis-Carrillo R, del Toro-Arreola S, Castellanos-Esparza YC, Bravo-Cuellar A. Pentoxifylline sensitizes human cervical tumor cells to cisplatin-induced apoptosis by suppressing NF-kappa B and de¬creased cell senescence. BMC Cancer 2011; 11: 483.

[09]    

Houlihan DD. Systematic review: pentoxifylline for the treatment of severe alcoholic hepatitis. Aliment Pharmacol Ther 2013; 37: 845-854.

[10]    

Li W, Zheng L, Sheng C, Cheng X, Qing L, Qu S. Systematic review on the treatment of pentoxi¬fylline in patients with non-alcoholic fatty liver disease. Lipids Health Dis 2011; 10: 49-59.

[11]    

Movassaghi S, Sharifi ZN, Mohammadzadeh F, Soleimani M. Pentoxifylline protects the rat liver against fibrosis and apoptosis induced by acute administration of 3, 4-Methylenedioxy-methamphetamine (MDMA or Ecstasy). Iran J Basic Med Sci 2013; 16: 922-927

[12]    

Nanji A A, Khettry U, Sadrzadeh S M. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver disease. Proc. Soc Exp Biol Med 1994; 205: 243–247.

[13]    

Goodman Z D. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. Journal of Hepatology 2007; 47: 598–60

[14]    

Xue W, Zender L, Miething C, Dickins R A, Hernando E, Krizhanovsky V, Cardo CC, Lowe S W. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445-8.

[15]    

Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.

[16]    

Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969; 27: 502-522.

[17]    

Slater TF, Sawyer BC. The stimulatory effect of carbon tetrachloride on peroxidative reactions in rat liver fraction in vitro. Inhibitory effects of freeradical scavengers and other agents. Biochem J. 1971; 123: 823-828.

[18]    

Nandi A, Chatterjee IB. Assay of superoxide dismutase activity in animal tissues. J Biosci. 1988; 13: 305-315.

[19]    

Herrera B, Murillo M M, Alvarez-Barrientos A. Source of early reactive oxygen species in the apoptosis induced by transforming growth factor-β in fetal rat hepatocytes. Free Radical Biol. Med 2004; 36: 16-26.

[20]    

Reinke LA, Moyer MJ. q-nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol. Drug Metab Dispos 1985; 13: 548–552

[21]    

Zhu R, Zeng G, Chen Y, Zhang Q, Liu B, Liu J, Chen H, Li M. Oroxylin A Accelerates Liver Regeneration in CCI4-Induced Acute Liver Injury Mice. PLOS ONE. 2013; 8: 8-71612.

[22]    

Shaw SM, Shah MK, Williams SG, Fildes JE. Immunological mechanisms of pentoxifylline in chronic heart failure. Eur J Heart Fail 2009; 11: 113-118.

[23]    

Movassaghi S, Sharifi ZN, Mohammadzadeh F, Soleimani M. Pentoxifylline Protects the Rat Liver Against Fibrosis and Apoptosis Induced by Acute Administration of 3, 4-Methylene-dioxymethamphetamine (MDMA or Ecstasy). Iran J Basic Med Sci 2013; 16: 922.

[24]    

Clark JM, Brancati FL, Diehl AM. The preva¬lence and etiology of elevated aminotransfer¬ase levels in the United States. Am J Gastroenterology 2003; 98: 960-967.

[25]    

Simpson KJ, Lukacs NW, Colletti L, Strieter RM, Kunkel SL. Cytokines and the liver. J Hepatol 1997; 27: 1120-1132

[26]    

Diao Y, Zhao XF, Lin JS, Wang QZ, Xu RA. Protection of the liver against CCl4-induced injury by intramuscular electrotransfer of a kal¬listatin-encoding plasmid. World J Gastroenterology 2011; 17: 111.

[27]    

Reyes-Gordillo K, Segovia J, Shibayama M, Vergara P, Moreno MG, Muriel P. Curcumin pro¬tects against acute liver damage in the rat by inhibiting NF-κB, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta 2007; 1770: 989-996.

[28]    

Demirel U, Yalnız M, Aygün C, Orhan C, Tuzcu M, Sahin K, Ozercan IH, Bahçecioğlu IH. Allopurinol ameliorates thioacetamide-induced acute liver failure by regulating cellular redox-sensitive transcription factors in rats. Inflammation 2012; 35: 1549-1557.

[29]    

Lerma-Díaz J M, Hernández-Flores G, Domínguez-Rodríguez JR, Ortíz-Lazareno PC, Gómez-Contreras P, Cervantes-Munguía R, Scott-Algara D, Aguilar-Lemarroy A, Jave-Suárez LF, Bravo-Cuellar A. In vivo and in vitro sensitization of leukemic cells to adriamycin-induced apoptosis by pentoxifylline: Involve-ment of caspase cascades and IκBα phosphorylation. Immunol Lett 2006; 103: 149-158.

[30]    

Hepgül G, Tanrıkulu S, Ünalp HR, Akguner T, Erbil Y, Olgaç V, Ademoğlu E. Preventive effect of pentoxifylline on acute radiation damage via antioxidant and anti-inflammatory pathways. Dig Dis Sci 2010; 55: 617-625.

[31]    

Santra A, Das S, Maity A. Prevention of carbone tetrachloride –induced hepatic injury in mice by Pichorhi Kurrooa. Indian journal of Gastroenterol. 1998; 7: 7.

[32]    

Kaya İ, Karapehlivan M, Yilmaz M. Investigation of effects on plasma nitric oxide, malondialde¬hyde and total sialic acid levels of glyphosate in Kars creek transcaucasian barb (Capoeta capoeta [Guldenstaedt, 1773]) in Turkey. Fresenius Environ Bull 2012; 21: 123-126.





 
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