Skip to main content
SpringerLink
Log in

Quercetin Prevents Oxidative Stress in Cirrhotic Rats

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Our aim was to study the protective effect of quercitin on liver cirrhosis induced by carbon tetrachloride (CCl4) in rats and its relationship with liver morphology. Thirty male Wistar rats weighing 200–250 g were randomly divided into three groups: control, CCl4, and CCl4+ quercetin. Rats in the experimental groups were given CCl4 (0.5 ml/kg i.p.), diluted 1:6 in vegetable oil (5 mmol/kg body wt), at 10:00 p.m. every 4 days for 17 weeks. Quercetin (500 μl/kg i.p.; 150 μmol/kg body wt) or vehicle was administered at 6:00 p.m. for the last 3 weeks of the study. Control group rats were given only olive oil for the same period. At the end of the 17 weeks, all rats were sacrificed. Blood samples were taken for determination of serum indicators (ALT, AST, total bilirubin, conjugated bilirubin, factor V) and the livers were dissected out and divided into two parts: one was homogenized and the supernatant was used for measurement of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities, as well as lipid peroxidation. The other part was used for the histopathological study. CCl4 caused a marked rise in serum levels of ALT, AST, total bilirubin, and conjugated bilirubin, as well as a decrease in factor V (P<0.05). Lipid peroxidation levels were significantly increased, whereas GSH, SOD, catalase, GPx, and GST levels were decreased in the liver of CCl4-treated rats. Quercetin (50 mg/kg/day) successfully attenuated these effects of CCl4. We conclude that quercetin has beneficial effects on liver fibrosis in rats by enhancing antioxidant enzyme activity and decreasing the pro-oxidant effect.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Recknagel RO, Glende EA, Hruszkewycz AM (1977) Chemical mechanisms in carbon tetrachloride toxicity. In: Free radicals in biology. Pryor WA (ed). Academic Press, New York, pp 97–132

    Google Scholar 

  2. Butler TC (1961) Reduction of carbon tetrachloride in vivo and reduction of carbon tetrachloride and chloroform in vitro by tissues and tissue constituents. J Pharmacol Exp Ther 134:311–319

    PubMed  CAS  Google Scholar 

  3. Fowler JSL (1969) Carbon tetrachloride metabolism in the rabbit. Br J Pharmacol 37:733–737

    PubMed  CAS  Google Scholar 

  4. Poyer JL, McCay PB, Lai EK, Jenzen EG, Davis ER (1980) Confirmation of assignment of the trichloromethyl radical spin adduct detected by spin trapping during 13C-carbon tetrachloride metabolism in vitro and in vivo. Biochem Biophys Res Commun 94:1154–1160

    Article  PubMed  CAS  Google Scholar 

  5. Packer JE, Slater TF, Willson RL (1978) Reactions of the carbon tetrachloride-related peroxy free radical with amino acids: pulse radiolysis evidence. Life Sci 23:2617–2620

    Article  PubMed  CAS  Google Scholar 

  6. Bonis P, Friedman SL, Kaplan MM (2001) Is liver fibrosis reversible. N Engl J Med 344(6):452–454

    Article  PubMed  CAS  Google Scholar 

  7. Perez-Tamayo R (1983) Is cirrhosis of the liver experimentally produced by CCl4 an adequate model of human cirrhosis? Hepatology 3:112–120

    Article  PubMed  CAS  Google Scholar 

  8. Formica JV, Regelson W (1995) Review of the biology of quercetin and related bioflavonoids. Food Chem Toxicol 33:1061–1080

    Article  PubMed  CAS  Google Scholar 

  9. Iwao K, Tsukamoto I (1999) Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upreglutation of p21WAF1C1P1 mRNA and protein expression during liver regeneration after partial hepatectomy. Biochim Biophys Acta 1427:112–120

    PubMed  CAS  Google Scholar 

  10. Sanders RA, Rauscher FM, Watkins JB (2001) Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 15:143–149

    Article  PubMed  CAS  Google Scholar 

  11. Pavanato A, Tuñón MJ, Sánchez-Campos S, Marroni CA, Llesuy S, González-Gallego J, Marroni N (2003) Effects of quercetin on liver damage in rats with carbon tetrachloride-induced cirrhosis. Dig Dis Sci 4:824–829

    Article  Google Scholar 

  12. Poli G, Parola M (1997) Oxidative damage and fibrogenesis. Free Rad Biol Med 22:287–305

    Article  PubMed  CAS  Google Scholar 

  13. Manach C, Texier O, Morand C, Crespy V, Regerat V, Demigne C, Remesy C (1999) Comparison of the bioavailability of quercetin and catechin in rats. Free Radic Biol Med 27:1259–1266

    Article  PubMed  CAS  Google Scholar 

  14. Park C, So H, Shin C, Baek S, Moon B, Shin S, Lee HS, Lee DW, Park R (2003) Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfuntion in H9c2 cardiomyoblast cells. Biochem Pharmacol 66(7):1287–1295

    Article  PubMed  CAS  Google Scholar 

  15. National Academy of Sciences (1991) The guiding principles for research involving animals. National Institutes of Health, Bethesada, MD

    Google Scholar 

  16. Llesuy SF, Milei J, Molina H, Boveris A, Milei S (1985) Comparison of lipid peroxidation and myocardial damage induced by adriamycin and 4’-epiadriamycin in mice. Tumori 71:241–249

    PubMed  CAS  Google Scholar 

  17. Fridovich I (1974) Superoxide and evolution. Horizons Biochem Biophys 1:1–18

    CAS  Google Scholar 

  18. Flohé L, Gunzler WA (1984) Assay of glutathione peroxidase. Methods Enzymol 105:114–121

    PubMed  Google Scholar 

  19. Beers RF Jr, Sizer IW (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195:133–140

    PubMed  CAS  Google Scholar 

  20. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–625

    PubMed  CAS  Google Scholar 

  21. Habig WH, Pabst MJ, Jakoby WB (1974) The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  22. Buege JÁ, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–309

    Article  PubMed  CAS  Google Scholar 

  23. Lowry OH, Rosebrough AL, Farr AL, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  24. Aleynik SI, Leo MA, Ma X, Aleynik MK, Lieber CS (1997) Polyenylphosphatidylcholine prevents carbon tetrachloride-induce lipid peroxidation while it attenuates. J Hepatol 27(3):554–561

    Article  PubMed  CAS  Google Scholar 

  25. Brattin WJ, Glende EA Jr, Recknagel RO (1985) Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med 1(1):27–38

    Article  PubMed  CAS  Google Scholar 

  26. Glende EA Jr, Recknagel RO (1991) An indirect method demonstrating that CCl4-dependent hepatocyte injury is linked to a rise in intracellular calcium ion concentration. Res Commun Chem Pathol Pharmacol 73(1):41–52

    PubMed  CAS  Google Scholar 

  27. Williams AT, Burk RF (1990) Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. Semin Liver Dis 10(4):279–284

    Article  PubMed  CAS  Google Scholar 

  28. Jeon TI, Hwang SG, Park NG, Jung YR, Shin SI, Choi SD, Park DK (2003) Antioxidative effect of chitosan on chronic carbon tetrachloride induced hepatic injury in rats. Toxicology 187:67–73

    Article  PubMed  CAS  Google Scholar 

  29. Fort J, Oberti F, Pilette C, Veal N, Gallois Y, Douay O, Rousselet MC, Rosenbaum CP (1998) Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide models of liver fibrosis in rats. Hepatology 28(6):1525–1531

    Article  PubMed  CAS  Google Scholar 

  30. Castilla-Cortazar I, Garcia M, Muguereza B, Quiroga J, Perez R, Santidrian S, Prieto J (1997) Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis. Gastroenterology 13:1682–1691

    Article  Google Scholar 

  31. Muriel P (1998) Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride. Biochem Pharmacol 56:773–779

    Article  PubMed  CAS  Google Scholar 

  32. Hernández-Muñhoz R, Diaz-Muñhoz M, Suárez-Cuena JÁ, Trejo-Solís C, López V, Sánchez-Sevilla Y, De Sánchez VC (2001) Adenosine reverses a preestablished CCl4-induced micronudular cirrhosis trhough enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. Hepatology 34(4):677–687

    Article  Google Scholar 

  33. García L, Hernádez I, Sandoval A, Salazar A, Garcia J, Vera J, Grijalva G, Muriel P, Margolin S, Armendariz-Borunda J (2002) Pirfenidone effectively reverses experimental liver fibrosis. J Hepatol 37:797–805

    Article  PubMed  Google Scholar 

  34. Peres W, Tuñón MJ, Collado PS, Matos SH, Marroni N, Gonzalez-Gallego J (2000) The flavonoid quercetin ameliorates liver damage in rats with biliary obstruction. J Hepatol 33:742–750

    Article  PubMed  CAS  Google Scholar 

  35. Brandão ABL, Marroni CA (2001) Testes de função hepática. In: Compêndio de Hepatologia., Mattos AA, Dantas W (eds). Fundação BYK, São Paulo

  36. Yokogawa K, Watanabe M, Takeshita H, Nomura M, Mano Y, Myamoto KI (2004) Serum aminotransferase activity as a predictor of clearance of drugs metabolized by CYP isoforms in rats with acute hepatic failure induced by carbon tetrachloride. Int J Pharm 269:479–489

    Article  PubMed  CAS  Google Scholar 

  37. Pastor A, Sánchez Collado P, Almar M, Barrientos C, González-Gallego J (1997) Antioxidant enzyme status in biliary obstructed rats: effects of S-adenosylmethionine. J Hepatol 27:363–367

    Article  PubMed  CAS  Google Scholar 

  38. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine. Oxford University Press, New York

    Google Scholar 

  39. Tappel AC (1973) Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874

    PubMed  CAS  Google Scholar 

  40. Lin CC, Yen MH, Lo TS, Lin JM (1998) Evaluation of the hepatoprotective and antioxidant activity of Boehmeria nivea var. nivea and B. nivea var. tenacissima. J Ethnopharmacol 60:9–17

    Article  PubMed  CAS  Google Scholar 

  41. Kadiiska MB, Gladen BC, Baird DD, Dikalova AE, Sohal R S, Hatch GE, Jones DP, Mason RP, Barrett JC (2000) Biomarkes of oxidative stress study: are plasma antioxidants markers of CCl4 poisoning? Free Rad Biol Med 28(6):838–845

    Article  PubMed  CAS  Google Scholar 

  42. Corrales F, Giménez A, Alvarez L, Caballería J, Pajares M A, Andreu H, Parés A, Mato JM, Rodés J (1992) S-Adenosylmethionine treatment prevents carbon tetrachloride-induced S-adenosylmethionine synthetase inactivationand attenuates liver injury. Hepatology 16:1022–1027

    Article  PubMed  CAS  Google Scholar 

  43. Gassó M, Rubio M, Varela G, Cabré M, Caballería J, Alonso E, Deulofem R, Camps, J, Giménez A, Pajares M, Parés A, Mato JM, Rodés J (1996) Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis. J Hepatol 25:200–205

    Article  PubMed  Google Scholar 

  44. Hernández-Muñhoz R, Díaz-Muñhoz M, López V, López-Barrera F, Yánez L, Vidrio S, Aranda-Fraustro A, Sánchez VC (1997) Balance between oxidative damage and proliferative potential in an experimental rat model of CCl4-induced cirrhosis: protective role of adenosine administration. Hepatology 26:1100–1110

    Google Scholar 

  45. Cabre M, Camps J, Paternain JL, Ferre N, Joven J (2000) Time-course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon tetrachloride-induced cirrhosis. Clin Exp Pharmacol Physiol 27(9):694–699

    Article  PubMed  CAS  Google Scholar 

  46. Lee MH, Yoon S, Moon JO (2004) The flavonoid naringenin inhibits dimethylnitrosamine-induced liver damage in rats. Biol Pharm Bull 27(1):72–76

    Article  PubMed  CAS  Google Scholar 

  47. Hsiao G, Lin YH, Lin CH, Chou DS, Lin WC, Sheu JR (2001) The protective effects of pmc against chronic carbon tetrachloride induced hepatotoxicity in vivo. Biol Pharm Bull 24(11):1271–1276

    Article  PubMed  CAS  Google Scholar 

  48. Murthy KNC, Jayaprakasha GK, Singh RP (2002) Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models. J Agr Food Chem 50:4791–4795

    Article  CAS  Google Scholar 

  49. Lee TY, Mai LM, Wang GJ, Chiu JH, Lin YL, Lin HC (2003) Protective mechanism of salvia miltiorrhiza on carbon tetrachloride-induced acute hepatotoxicity in rats. J Pharmacol Sci 91:202–210

    Article  PubMed  CAS  Google Scholar 

  50. Flohé L, Gunzler Wa, Schock HH (1973) Glutathione peroxidase: a seleno-enzyme. Febs Lett 32:132–134

    Article  PubMed  Google Scholar 

  51. Jakoby WB (1988) Detoxification, conjugation and hydrolysis in liver biology and pathology. Raven Press, New York

    Google Scholar 

  52. Gaudio E, Onori P, Franchitto A, Sferra R, Riggio O (1997) Liver metabolic zonation and hepatic microcirculation in carbon tetrachloride-induced experimental cirrhosis. Dig Dis Sci 42(1):167–177

    Article  PubMed  CAS  Google Scholar 

  53. Schuppan D, Bauer M, Krebs A, Hahn EG (2001) Antifibrogenic treatment- present status and future directions. In: Therapy in hepatology. Arroyo V, Bosch J, Bruix J, Ginés P, Navasa M, Rodés J (eds). Ars Medica, Barcelona, pp 395–405

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, Brazil

    Pavanato Maria Amália & Llesuy Susana Francisca

  2. Laboratório de Hepatologia Experimental–Fisiologia, Federal University of Rio Grande do Sul-Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

    Marroni Norma Possa

  3. University Luterana of Brazil, Canoas, RS, Brazil

    Marroni Norma Possa

  4. Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Serviço de Gastroenterologia/Hepatologia, Porto Alegre, RS, Brazil

    Marroni Claúdio Augusto

  5. Departamento de Fisiologia e Farmacologia, Universidade Federal de Santa Maria, Predio 21, Campus Universitario, Faixa Camobi-Km 9, Santa Maria, RS, Brazil

    Llesuy Susana Francisca

Authors
  1. Pavanato Maria Amália
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marroni Norma Possa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marroni Claúdio Augusto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Llesuy Susana Francisca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Llesuy Susana Francisca.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Amália, P.M., Possa, M.N., Augusto, M.C. et al. Quercetin Prevents Oxidative Stress in Cirrhotic Rats. Dig Dis Sci 52, 2616–2621 (2007). https://doi.org/10.1007/s10620-007-9748-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-007-9748-x

Keywords

Search

Navigation