« Previous Article
Next Article »

Original Article Open Access


Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C

Aziza A. Saad, El-Hassan M. Mokhamer, Mohamed A. Abdel Mohsen, Geylan A. Fadaly.

Abstract
Objective: Mounting clinical and experimental evidence has demonstrated that even advanced fibrosis and cirrhosis are reversible. Thus there is a considerable imperative to develop antifibrotic strategies that are applicable to liver fibrosis. In the present study, the attenuation of carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats through the co-treatment with antioxidant vitamins C and E or glycine alone was investigated.
Methods: Sixty male albino rats were divided randomly into control, CCl4, vitamin E+C and glycine groups. Except for the control group, all rats in the other groups received orally 2 ml/kg CCl4 dissolved in olive oil (1:1, v/v) twice a week; antioxidant vitamins were supplemented orally (p.o.) at a dose of 200 IU/kg/day vitamin E and 50 mg/kg/day vitamin C. Glycine dose was 0.6 g/Kg/day (p.o.). After nine weeks all rats were sacrificed for biochemical and histopathological investigations.
Results: Serum levels of hepatic transaminases, alkaline phospatase, gamma glutamyl transferase and β-glucuronidase strikingly increased in CCl4 group. As biomarker of fibrinogenesis, hyaluronic acid was significantly elevated. These were associated with drastic significant decline in serum albumin concentration level, blood glutathione content, glutathione peroxidase, catalase and superoxide dismutase enzymatic activities as well as a striking significant increase in the concentration of serum malondialdehyde. A significant increase in the mean serum concentration levels of tumor necrosis factor- and transforming growth factor-1 has been observed in CCl4-treated rats. Histopathological examination highlighted and confirmed the biochemical results.
Conclusion: The results of this study confirmed the ameliorative effects of vitamin E plus C combination and glycine supplements against liver fibrosis in rats induced by CCl4

Key words: Antioxidants, carbon tetrachloride, glycine, hepatic fibrosis, oxidative stress


 
ARTICLE TOOLS
Abstract
PDF Fulltext
Print this article Print this Article
How to cite this articleHow to cite this article
Export to
Export to
Related Records
 Articles by Aziza A. Saad
Articles by El-Hassan M. Mokhamer
Articles by Mohamed A. Abdel Mohsen
Articles by Geylan A. Fadaly
on Google
on Google Scholar
Article Statistics
 Viewed: 1712
Downloaded: 526
Cited: 0

REFERENCES
1. Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis. AnnuRev Pathol 2011;6:425-56. [DOI via Crossref]    [Pubmed]   
2. Mas VR, Fisher RA, Archer KJ, Maluf DG. Proteomics and liverfibrosis: Identifying markers of fibrogenesis. Expert Rev Proteomics2009;6:421-31. [DOI via Crossref]    [Pubmed]   
3. Iredale JP. Models of liver fibrosis: Exploring the dynamic nature ofinflammation and repair in a solid organ. J Clin Invest 2007;117:539-48. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
4. Boobis AR, Fawthrop DJ, Davies DS. Mechanisms of cell death.Trends Pharmacol Sci 1989;10:275-80. [DOI via Crossref]   
5. Lamireau T, Desmoulière A, Bioulac-Sage P, Rosenbaum J.Mechanisms of hepatic fibrogenesis. Arch Pediatr 2002;9:392-405. [DOI via Crossref]   
6. Nadkarni GD, D’Souza NB. Hepatic antioxidant enzymes and lipidperoxidation in carbon tetrachloride-induced liver cirrhosis in rats.Biochem Med Metab Biol 1988;40:42-5. [DOI via Crossref]   
7. Simeonova PP, Gallucci RM, Hulderman T, Wilson R, Kommineni C,Rao M, et al. The role of tumor necrosis factor-alpha in liver toxicity,inflammation, and fibrosis induced by carbon tetrachloride. ToxicolAppl Pharmacol 2001;177:112-20. [DOI via Crossref]    [Pubmed]   
8. Adikwu E, Deo O. Hepatoprotective effect of vitamin C (Ascorbicacid). Pharmacol Pharm 2013;4:84-92. [DOI via Crossref]   
9. Traber MG, Atkinson J. Vitamin E, antioxidant and nothing more. FreeRadic Biol Med 2007;43:4-15. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
10. Bi W, Wang F, Bi Y, Wang T, Xue P, Zhang Y, et al. Renal ischemia/reperfusion injury in rats is attenuated by a synthetic glycinederivative. Eur J Pharmacol 2009;616:256-64. [DOI via Crossref]    [Pubmed]   
11. Rentsch M, Beham A, Sirek S, Iesalnieks I, Geissler EK, Anthuber M,et al. Glycine but not gadolinium chloride or methyl palmitate reducespostischemic white blood cell accumulation and early graftnonfunction after liver transplantation in the rat. Transplant Proc2002;34:2389-90. [DOI via Crossref]   
12. Fishman WH, Kato K, Anstiss CL, Green S. Human serum betaglucuronidase;its measurement and some of its properties. ClinChim Acta 1967;15:435-47. [DOI via Crossref]   
13. Satoh K. Serum lipid peroxide in cerebrovascular disorders determinedby a new colorimetric method. Clin Chim Acta 1978;90:37-43. [DOI via Crossref]   
14. Beutler E, Duron O, Kelly BM. Improved method for the determinationof blood glutathione. J Lab Clin Med 1963;61:882-8. [Pubmed]   
15. Paglia DE, Valentine WN. Studies on the quantitative and qualitativecharacterization of erythrocyte glutathione peroxidase. J Lab ClinMed 1967;70:158-69. [Pubmed]   
16. Marklund S, Marklund G. Involvement of the superoxide anionradical in the autoxidation of pyrogallol and a convenient assay forsuperoxide dismutase. Eur J Biochem 1974;47:469-74. [DOI via Crossref]   
17. Beers RF Jr, Sizer IW. A spectrophotometric method for measuringthe breakdown of hydrogen peroxide by catalase. J Biol Chem1952;195:133-40. [Pubmed]   
18. Edwards MJ, Keller BJ, Kauffman FC, Thurman RG. The involvementof Kupffer cells in carbon tetrachloride toxicity. Toxicol Appl Pharmacol1993;119:275-9. [DOI via Crossref]    [Pubmed]   
19. Wolfgang GH, Jolly RA, Donarski WJ, Ochoa R, Petry TW. Inhibition ofcarbon tetrachloride-induced lipid peroxidation by novel antioxidantsin rat hepatic microsomes: Dissociation from hepatoprotectiveeffects in vivo. J Biochem Toxicol 1990;5:167-74. [DOI via Crossref]    [Pubmed]   
20. Lin HM, Tseng HC, Wang CJ, Lin JJ, Lo CW, Chou FP. Hepatoprotectiveeffects of Solanum nigrum Linn extract against CCl(4)-inducedoxidative damage in rats. Chem Biol Interact 2008;171:283-93. [DOI via Crossref]    [Pubmed]   
21. Abraham P. Lysosomal enzyme activity during development of carbontetrachloride induced cirrhosis in rats. Indian J Physiol Pharmacol2004;48:206-12. [Pubmed]   
22. George J. Elevated serum beta-glucuronidase reflects hepaticlysosomal fragility following toxic liver injury in rats. Biochem CellBiol 2008;86:235-43. [DOI via Crossref]    [Pubmed]   
23. Bodakhe SH, Ram A. Hepatoprotective properties of Bauhiniavariegata bark extract. Yakugaku Zasshi 2007;127:1503-7. [DOI via Crossref]   
24. Hicks SJ, Drysdale JW, Munro HN. Preferential synthesis of ferritinand albumin by different populations of liver polysomes. Science1969;164:584-5. [DOI via Crossref]    [Pubmed]   
25. Lin WC, Lin WL. Ameliorative effect of Ganoderma lucidum on carbontetrachloride-induced liver fibrosis in rats. World J Gastroenterol2006;12:265-70. [Pubmed]    [PMC Free Fulltext]   
26. Wang R, Yu XY, Guo ZY, Wang YJ, Wu Y, Yuan YF. Inhibitory effectsof salvianolic acid B on CCl(4)-induced hepatic fibrosis throughregulating NF-?B/I?Ba signaling. J Ethnopharmacol 2012;144:592-8. [DOI via Crossref]    [Pubmed]   
27. George J, Tsutsumi M, Takase S. Expression of hyaluronic acidin N-nitrosodimethylamine induced hepatic fibrosis in rats. Int JBiochem Cell Biol 2004;36:307-19. [DOI via Crossref]   
28. Vrochides D, Papanikolaou V, Pertoft H, Antoniades AA, Heldin P.Biosynthesis and degradation of hyaluronan by nonparenchymalliver cells during liver regeneration. Hepatology 1996;23:1650-5. [DOI via Crossref]    [Pubmed]   
29. Ueno T, Inuzuka S, Torimura T, Tamaki S, Koh H, Kin M, et al.Serum hyaluronate reflects hepatic sinusoidal capillarization.Gastroenterology 1993;105:475-81. [Pubmed]   
30. Xie SB, Yao JL, Zheng SS, Yao CL, Zheng RQ. The levels of serumfibrosis marks and morphometric quantitative measurement ofhepatic fibrosis. Hepatobiliary Pancreat Dis Int 2002;1:202-6. [Pubmed]   
31. Kuzu N, Metin K, Dagli AF, Akdemir F, Orhan C, Yalniz M, et al.Protective role of genistein in acute liver damage induced by carbontetrachloride. Mediators Inflamm 2007;2007:36381. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
32. Uskokovic-Markovic S, Milenkovic M, Topic A, Kotur-Stevuljevic J, Stefanovic A, Antic-Stankovic J. Protective effects oftungstophosphoric acid and sodium tungstate on chemically inducedliver necrosis in wistar rats. J Pharm Pharm Sci 2007;10:340-9. [Pubmed]   
33. Aoyama K, Matsumura N, Watabe M, Nakaki T. Oxidative stress onEAAC1 is involved in MPTP-induced glutathione depletion and motordysfunction. Eur J Neurosci 2008;27:20-30. [DOI via Crossref]    [Pubmed]   
34. Yao HW, Li J, Chen JQ, Xu SY. Inhibitory effect of leflunomideon hepatic fibrosis induced by CCl4 in rats. Acta Pharmacol Sin2004;25:915-20. [Pubmed]   
35. Calò L, Giacon B, Davis PA, Pagnin E, Piccin A, Riegler P, et al.Oxidative stress and TGFbeta in kidney-transplanted patients withcyclosporin-induced hypertension. Effect of carvedilol and nifedipine.Clin Nephrol 2002;58:103-10. [DOI via Crossref]    [Pubmed]   
36. Friedman SL. Hepatic stellate cells: Protean, multifunctional, andenigmatic cells of the liver. Physiol Rev 2008;88:125-72. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
37. Brouckaert P, Fiers W. Tumor necrosis factor and the systemicinflammatory response syndrome. Curr Top Microbiol Immunol1996;216:167-87. [DOI via Crossref]    [Pubmed]   
38. Osawa Y, Hoshi M, Yasuda I, Saibara T, Moriwaki H, Kozawa O. Tumornecrosis factor-a promotes cholestasis-induced liver fibrosis in themouse through tissue inhibitor of metalloproteinase-1 production inhepatic stellate cells. PLoS One 2013;8:e65251. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
39. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGFbetain hepatic fibrosis. Front Biosci 2002;7:d793-807. [DOI via Crossref]    [Pubmed]   
40. Bashandy AS, Alwasel SH. Carbon tetrachloride-induced hepatotoxicityand nephrotoxicity in rats: Protective role of vitamin C. J PharmacolToxicol 2011;6:283-92.
41. Neuzil J, Witting PK, Stocker R. Alpha-tocopheryl hydroquinone is anefficient multifunctional inhibitor of radical-initiated oxidation of lowdensity lipoprotein lipids. Proc Natl Acad Sci U S A 1997;94:7885-90. [DOI via Crossref]    [Pubmed]    [PMC Free Fulltext]   
42. Tawfik M, Al-Badr N. Adverse effects of monosodium glutamate onliver and kidney functions in adult rats and potential protective effectof vitamins C and E. Food Nutr Sci 2012;3:651-9. [DOI via Crossref]   
43. Uboh FE, Ebong PE, Akpan HD, Usoh IF. Hepatoprotective effect ofvitamin C and E against gasoline vapour induced liver injury in malerats. Turk J Biol 2012;36:217-23.
44. Yin M, Ikejima K, Arteel GE, Seabra V, Bradford BU, Kono H,et al. Glycine accelerates recovery from alcohol-induced liver injury.J Pharmacol Exp Ther 1998;286:1014-9. [Pubmed]   
45. Garcia-Macedo R, Sanchez-Mu-oz F, Almanza-Perez JC, Duran-Reyes G, Alarcon-Aguilar F, Cruz M. Glycine increases mRNAadiponectin and diminishes pro-inflammatory adipokines expressionin 3T3-L1 cells. Eur J Pharmacol 2008;587:317-21. [DOI via Crossref]    [Pubmed]   

How to Cite this Article
Pubmed Style

Saad AA, Mokhamer EM, Mohsen MAA, Fadaly GA. Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. J Exp Integr Med. 2014; 4(3): 180-186. doi:10.5455/jeim.150514.or.104



Web Style

Saad AA, Mokhamer EM, Mohsen MAA, Fadaly GA. Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. www.scopemed.org/?mno=156475 [Access: May 29, 2017]. doi:10.5455/jeim.150514.or.104



AMA (American Medical Association) Style

Saad AA, Mokhamer EM, Mohsen MAA, Fadaly GA. Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. J Exp Integr Med. 2014; 4(3): 180-186. doi:10.5455/jeim.150514.or.104



Vancouver/ICMJE Style

Saad AA, Mokhamer EM, Mohsen MAA, Fadaly GA. Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. J Exp Integr Med. (2014), [cited May 29, 2017]; 4(3): 180-186. doi:10.5455/jeim.150514.or.104



Harvard Style

Saad, A. A., Mokhamer, E. M., Mohsen, M. A. A. & Fadaly, G. A. (2014) Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. J Exp Integr Med, 4 (3), 180-186. doi:10.5455/jeim.150514.or.104



Turabian Style

Saad, Aziza A., El-Hassan M. Mokhamer, Mohamed A. Abdel Mohsen, and Geylan A. Fadaly. 2014. Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. Journal of Experimental and Integrative Medicine, 4 (3), 180-186. doi:10.5455/jeim.150514.or.104



Chicago Style

Saad, Aziza A., El-Hassan M. Mokhamer, Mohamed A. Abdel Mohsen, and Geylan A. Fadaly. "Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C." Journal of Experimental and Integrative Medicine 4 (2014), 180-186. doi:10.5455/jeim.150514.or.104



MLA (The Modern Language Association) Style

Saad, Aziza A., El-Hassan M. Mokhamer, Mohamed A. Abdel Mohsen, and Geylan A. Fadaly. "Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C." Journal of Experimental and Integrative Medicine 4.3 (2014), 180-186. Print. doi:10.5455/jeim.150514.or.104



APA (American Psychological Association) Style

Saad, A. A., Mokhamer, E. M., Mohsen, M. A. A. & Fadaly, G. A. (2014) Attenuation of carbon tetrachloride-induced hepatic fibrosis by glycine, vitamin E and vitamin C. Journal of Experimental and Integrative Medicine, 4 (3), 180-186. doi:10.5455/jeim.150514.or.104