Skip to main content
SpringerLink
Log in

Increased Plasma Malondialdehyde in Patients with Viral Cirrhosis and Its Relationships to Plasma Nitric Oxide, Endotoxin, and Portal Pressure

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

Abstract

Background and Aim

Increased oxidative stress is involved in the development of portal hypertension in cirrhosis. Our study aimed to assess the relationship between oxidative stress and hemodynamic parameters in cirrhotic patients.

Methods

Forty-two patients with viral cirrhosis and 24 normal controls were enrolled. Measurements of plasma levels of malondialdehyde (MDA), nitrite/nitrate (NOx), endotoxin, and activities of superoxide dismutase (SOD) were carried out in all subjects. Systemic and splanchnic hemodynamic measurements were carried out in cirrhotic patients.

Results

Plasma levels of MDA, endotoxin, and NOx were significantly higher in cirrhotic patients than in normal controls (900 ± 751 versus 226 ± 16 nM, P < 0.01; 62.0 ± 26.0 versus 14.8 ± 4.1 pg/mL, P < 0.01; 50.5 ± 22.6 versus 15.0 ± 9.2 nM, P < 0.01, respectively). Activities of SOD were significantly decreased in cirrhotic patients compared with in normal controls (2.62 ± 0.7 versus 6.8 ± 0.4 U/mL). Further, plasma levels of MDA in cirrhotic patients were significantly positively associated with hepatic venous pressure gradient (HVPG) (r = 0.35; P = 0.025), wedge hepatic venous pressure (WHVP) (r = 0.42; P = 0.007), and hepatic sinusoid resistance (HSR) (r = 0.33; P = 0.033). Plasma MDA levels also correlated positively with plasma endotoxin (r = 0.71, P < 0.001) and NOx (r = 0.55, P < 0.001) levels in the cirrhotic patients. Multiregression analysis showed that the independent and strongest factors to predict HVPG, WHVP, and HSR are plasma levels of NOx, MDA, and endotoxin, respectively.

Conclusion

This study suggests a close interaction among MDA, endotoxin, and NOx and that these substances are also associated with hemodynamic derangement in cirrhosis.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Adam-Vizi V, Chinopoulos C. Bioenergetics and the formation of mitochondrial reactive oxygen species. Trends Pharmacol Sci. 2006;27:639–645.

    Article  CAS  PubMed  Google Scholar 

  2. Cave AC, Brewer AC, Narayanapanicker A, et al. NADPH oxidases in cardiovascular health and disease. Antioxid Redox Signal. 2006;8:691–728.

    Article  CAS  PubMed  Google Scholar 

  3. Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health. 2003;27:277–284.

    PubMed  Google Scholar 

  4. Rodriguez-Vilarrupla A, Bosch J, Garcia-Pagan JC. Potential role of antioxidants in the treatment of portal hypertension. J Hepatol. 2007;46:193–197.

    Article  CAS  PubMed  Google Scholar 

  5. Cadenas E. Biochemistry of oxygen toxicity. Annu Rev Biochem. 1989;58:79–110.

    Article  CAS  PubMed  Google Scholar 

  6. Bosch J, Garcia-Pagan JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol. 2000;32:141–156.

    Article  CAS  PubMed  Google Scholar 

  7. Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol. 2001;35:297–306.

    Article  CAS  PubMed  Google Scholar 

  8. Marley R, Holt S, Fernando B, et al. Lipoic acid prevents development of the hyperdynamic circulation in anesthetized rats with biliary cirrhosis. Hepatology. 1999;29:1358–1363.

    Article  CAS  PubMed  Google Scholar 

  9. Fernando B, Marley R, Holt S, et al. N-acetylcysteine prevents development of the hyperdynamic circulation in the portal hypertensive rat. Hepatology. 1998;28:689–694.

    Article  CAS  PubMed  Google Scholar 

  10. Yang YY, Lee KC, Huang YT, et al. Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis. J Hepatol. 2008;49:25–33.

    Article  CAS  PubMed  Google Scholar 

  11. Hernandez-Guerra M, Garcia-Pagan JC, Turnes J, et al. Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension. Hepatology. 2006;43:485–491.

    Article  CAS  PubMed  Google Scholar 

  12. Aboutwerat A, Pemberton PW, Smith A, et al. Oxidant stress is a significant feature of primary biliary cirrhosis. Biochim Biophys Acta. 2003;1637:142–150.

    CAS  PubMed  Google Scholar 

  13. Nalini G, Hariprasad C, Narayanan VA. Oxidative stress in alcoholic liver disease. Indian J Med Res. 1999;110:200–203.

    CAS  PubMed  Google Scholar 

  14. Jain SK, Pemberton PW, Smith A, et al. Oxidative stress in chronic hepatitis C: Not just a feature of late stage disease. J Hepatol. 2002;36:805–811.

    Article  CAS  PubMed  Google Scholar 

  15. Clot P, Tabone M, Arico S, Albano E. Monitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake. Gut. 1994;35:1637–1643.

    Article  CAS  PubMed  Google Scholar 

  16. Goulis J, Patch D, Burroughs AK. Bacterial infection in the pathogenesis of variceal bleeding. Lancet. 1999;353:139–142.

    Article  CAS  PubMed  Google Scholar 

  17. Guarner C, Soriano G, Tomas A, et al. Increased serum nitrite and nitrate levels in patients with cirrhosis: Relationship to endotoxemia. Hepatology. 1993;18:1139–1143.

    Article  CAS  PubMed  Google Scholar 

  18. Iwakiri Y, Groszmann RJ. The hyperdynamic circulation of chronic liver diseases: From the patient to the molecule. Hepatology. 2006;43:S121–S131.

    Article  CAS  PubMed  Google Scholar 

  19. Wang YW, Hou TI, Yang YY, et al. Correlation and comparison of the model for end-stage liver disease, portal pressure, and serum sodium or outcome prediction in patients with liver cirrhosis. J Clin Gastroenterol. 2007;41:706–712.

    Article  PubMed  Google Scholar 

  20. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med. 2004;350:1646–1654.

    Article  CAS  PubMed  Google Scholar 

  21. Lin HC, Tsai YT, Lee FY, et al. Hemodynamic evaluation of octreotide in patients with hepatitis B-related cirrhosis. Gastroenterology. 1992;103:229–234.

    CAS  PubMed  Google Scholar 

  22. Yesilova Z, Yaman H, Oktenli C, et al. Systemic markers of lipid peroxidation and antioxidants in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2005;100:850–855.

    Article  CAS  PubMed  Google Scholar 

  23. Moncada S, Higgs A. The l-arginine-nitric oxide pathway. N Engl J Med. 1993;329:2002–2012.

    Article  CAS  PubMed  Google Scholar 

  24. Toh Y, Korenaga D, Maekawa S, et al. Assessing the permeability of the gastrointestinal mucosa after oral administration of phenolsulfonphthalein. Hepatogastroenterology. 1997;44:1147–1151.

    CAS  PubMed  Google Scholar 

  25. Ramachandran A, Prabhu R, Thomas S, Reddy JB, Pulimood A, Balasubramanian KA. Intestinal mucosal alterations in experimental cirrhosis in the rat: Role of oxygen free radicals. Hepatology. 2002;35:622–629.

    Article  CAS  PubMed  Google Scholar 

  26. Schimpl G, Pesendorfer P, Steinwender G, Feierl G, Ratschek M, Hollwarth ME. Allopurinol and glutamine attenuate bacterial translocation in chronic portal hypertensive and common bile duct ligated growing rats. Gut. 1996;39:48–53.

    Article  CAS  PubMed  Google Scholar 

  27. Yoshikawa T, Takano H, Takahashi S, Ichikawa H, Kondo M. Changes in tissue antioxidant enzyme activities and lipid peroxides in endotoxin-induced multiple organ failure. Circ Shock. 1994;42:53–58.

    CAS  PubMed  Google Scholar 

  28. Portoles MT, Ainaga MJ, Pagani R. The induction of lipid peroxidation by E. coli lipopolysaccharide on rat hepatocytes as an important factor in the etiology of endotoxic liver damage. Biochim Biophys Acta. 1993;1158:287–292.

    CAS  PubMed  Google Scholar 

  29. Dogru-Abbasoglu S, Parildar-Karpuzoglu H, Balkan J, Aykac-Toker G, Uysal M. Nitrotyrosine formation and heme oxygenase-1 expression in endotoxemic cirrhotic rats. Arch Med Res. 2007;38:28–33.

    Article  CAS  PubMed  Google Scholar 

  30. Huie RE, Padmaja S. The reaction of NO with superoxide. Free Radic Res Commun. 1993;18:195–199.

    Article  CAS  PubMed  Google Scholar 

  31. Radi R, Beckman JS, Bush KM, Freeman BA. Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 1991;288:481–487.

    Article  CAS  PubMed  Google Scholar 

  32. Rodriguez-Martinez MA, Martinez-Orgado J, Salaices M, Marin J. Impairment of acetylcholine relaxations by malondialdehyde, a marker of lipid peroxidation. J Vasc Res. 1996;33:463–470.

    CAS  PubMed  Google Scholar 

  33. Parola M, Leonarduzzi G, Robino G, Albano E, Poli G, Dianzani MU. On the role of lipid peroxidation in the pathogenesis of liver damage induced by long-standing cholestasis. Free Radic Biol Med. 1996;20:351–359.

    Article  CAS  PubMed  Google Scholar 

  34. Miller AM, Masrorpour M, Klaus C, Zhang JX. LPS exacerbates endothelin-1 induced activation of cytosolic phospholipase A2 and thromboxane A2 production from Kupffer cells of the prefibrotic rat liver. J Hepatol. 2007;46:276–285.

    Article  CAS  PubMed  Google Scholar 

  35. Rockey DC, Weisiger RA. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: Implications for regulation of portal pressure and resistance. Hepatology. 1996;24:233–240.

    Article  CAS  PubMed  Google Scholar 

  36. Bianchi G, Marchesini G, Fabbri A, Ronchi M, Chianese R, Grossi G. Lipoperoxide plasma levels in patients with liver cirrhosis. Hepatogastroenterology. 1997;44:784–788.

    CAS  PubMed  Google Scholar 

  37. Trevisani F, Caraceni P, Simoncini M, et al. Evidence of oxidative imbalance in long-term liver transplant patients. Dig Liver Dis. 2002;34:279–284.

    Article  CAS  PubMed  Google Scholar 

  38. Yamamoto Y, Yamashita S, Fujisawa A, Kokura S, Yoshikawa T. Oxidative stress in patients with hepatitis, cirrhosis, and hepatoma evaluated by plasma antioxidants. Biochem Biophys Res Commun. 1998;247:166–170.

    Article  CAS  PubMed  Google Scholar 

  39. Paradis V, Mathurin P, Kollinger M, et al. In situ detection of lipid peroxidation in chronic hepatitis C: Correlation with pathological features. J Clin Pathol. 1997;50:401–406.

    Article  CAS  PubMed  Google Scholar 

  40. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–851.

    Article  CAS  PubMed  Google Scholar 

  41. Szuster-Ciesielska A, Daniluk J, Kandefer-Szerszen M. Oxidative stress in the blood of patients with alcohol-related liver cirrhosis. Med Sci Monit. 2002;8:CR419–CR424.

    PubMed  Google Scholar 

  42. Matoba T, Shimokawa H, Kubota H, et al. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in human mesenteric arteries. Biochem Biophys Res Commun. 2002;290:909–913.

    Article  CAS  PubMed  Google Scholar 

  43. Bauersachs J, Popp R, Hecker M, Sauer E, Fleming I, Busse R. Nitric oxide attenuates the release of endothelium-derived hyperpolarizing factor. Circulation. 1996;94:3341–3347.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Peng Chi-Yi and Judy Huang for their excellent technical assistance. This work was supported by grants NSC96-2314-B-075-018-MY3 and NSC96-2314-B-075-035 from the National Science Council of the Republic of China, Taiwan and grants V96C1-005 and VGH96B1-001 from the Taipei Veterans General Hospital, Taipei, Taiwan.

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, 11217, Taiwan

    Kuei-Chuan Lee, Ying-Wen Wang, Ming-Chih Hou, Han-Chieh Lin & Shou-Dong Lee

  2. Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

    Ying-Ying Yang & Fa-Yauh Lee

  3. Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Kuei-Chuan Lee, Ying-Ying Yang, Ying-Wen Wang, Fa-Yauh Lee, Che-Chuan Loong, Ming-Chih Hou, Han-Chieh Lin & Shou-Dong Lee

  4. Institute of Public Health, Department of Preventive Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan

    Ying-Ying Yang

  5. Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Che-Chuan Loong

Authors
  1. Kuei-Chuan Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ying-Ying Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying-Wen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fa-Yauh Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Che-Chuan Loong
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ming-Chih Hou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Han-Chieh Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Shou-Dong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Han-Chieh Lin.

Additional information

Kuei-Chuan Lee and Ying-Ying Yang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, KC., Yang, YY., Wang, YW. et al. Increased Plasma Malondialdehyde in Patients with Viral Cirrhosis and Its Relationships to Plasma Nitric Oxide, Endotoxin, and Portal Pressure. Dig Dis Sci 55, 2077–2085 (2010). https://doi.org/10.1007/s10620-009-0990-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-009-0990-2

Keywords

Search

Navigation