Skip to main content
SpringerLink
Log in

Protective Effects of Ulinastatin on Acute Liver Failure Induced by Lipopolysaccharide/d-Galactosamine

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

Abstract

Background

Although treatment of acute liver failure has been improved significantly recently, the survival rate of acute liver failure is only 5–20%. Therefore, prevention and treatment of acute liver failure are still urgent issues in the field of liver disease.

Aims

It has been demonstrated that ulinastatin could attenuate acute injury of internal organs from endotoxin. This study evaluates whether ulinastatin can prevent and/or attenuate acute liver failure induced by the combination of lipopolysaccharide and d-galactosamine (LPS/d-gal).

Methods

Sprague–Dawley rats were employed to induce acute liver failure by injection of LPS/d-gal. The liver function, inflammatory factors, oxidative stress index, and hepatic histopathological alteration were examined in the rats with and without ulinastatin treatment.

Results

In rats treated with LPS/d-gal, there were increases in the levels of ALT and AST in the serum and levels of malondialdehyde and inducible nitric oxide synthase in liver tissues. Moreover, the levels of antioxidants such as superoxide dismutase and glutathione peroxidase were reduced in the liver. Furthermore, inflammatory factors (TNF-alpha and IL-6) and apoptotic enzyme (caspase-3) were increased in the respective serum and liver of rats treated with LPS/d-gal. However, pre-treatment of ulinastatin significantly reversed all of these parameters in the rats that received LPS/d-gal alone.

Conclusions

The finding in this study suggests that ulinastatin could be a potential agent for prevention and treatment of acute liver injury induced by LPS/d-gal.

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
Fig. 5

Similar content being viewed by others

References

  1. Kim SH, Heo JH, Kim YS, Kang SS, Choi JS, Lee SM. Protective effect of daidzin against d-galactosamine and lipopolysaccharide-induced hepatic failure in mice. Phytother Res. 2008;23:701–706.

    Article  Google Scholar 

  2. Kaur G, Tirkey N, Bharrhan S, Chanana V, Rishi P, Chopra K. Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin-induced experimental hepatoxicity in rodents. Clin Exp Immunol. 2006;145:313–321.

    Article  PubMed  CAS  Google Scholar 

  3. Ravikumar V, Shivashangari KS, Devaki T. Effect of Tridax procumbens on liver antioxidant defense system during lipopolysaccharide-induced hepatitis in d-galactosamine sensitised rats. Mol Cell Biochem. 2005;269:131–136.

    Article  PubMed  CAS  Google Scholar 

  4. Mehanna A, Vitorino DC, Panis C, Blanco EE, Pinge-Filho P, Martins-Pinge MC. Cardiovascular and pulmonary effects of NOS inhibition in endotoxemic conscious rats subjected to swimming training. Life Sci. 2007;81:1301–1308.

    Article  PubMed  CAS  Google Scholar 

  5. Huang Y, Xie K, Zhang J, Dang Y, Qiong Z. Prospective clinical and experimental studies on the cardioprotective effect of ulinastatin following severe burns. Burns. 2008;34:674–680.

    Article  PubMed  Google Scholar 

  6. Cao ZL, Okazaki Y, Naito K, Ueno T, Natsuaki M, Itoh T. Ulinastatin attenuates reperfusion injury in the isolated blood-perfused rabbit heart. Ann Thorac Surg. 2000;69:1121–1126.

    Article  PubMed  CAS  Google Scholar 

  7. Gurtu V, Kain SR, Zhang G. Fluorometric and colorimetric detection of caspase activity associated with apoptosis. Anal Biochem. 1997;251:98–102.

    Article  PubMed  CAS  Google Scholar 

  8. Koizumi R, Kanai H, Maezawa A, Kanda T, Nojima Y, Naruse T. Therapeutic effects of ulinastatin on experimental crescentic glomerulonephritis in rats. Nephron. 2000;84:347–353.

    Article  PubMed  CAS  Google Scholar 

  9. Sakaguchi T, Nakamura S, Suzuki S, et al. Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats. Hepatology. 1999;30:959–967.

    Article  PubMed  CAS  Google Scholar 

  10. Aihara T, Shiraishi M, Hiroyasu S, et al. Ulinastatin: a protease inhibitor, attenuates hepatic ischemia/reperfusion injury by downregulating TNF-alpha in the liver. Transpl Proc. 1998;30:3732–3734.

    Article  CAS  Google Scholar 

  11. Banerjee A, Russell WK, Jayaraman A, Ramaiah SK. Identification of proteins to predict the molecular basis for the observed gender susceptibility in a rat model of alcoholic steatohepatitis by 2-D gel proteomics. Proteomics. 2008;8:4327–4337.

    Article  PubMed  CAS  Google Scholar 

  12. Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ. Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia. Am J Physiol. 1993;264:G801–G809.

    PubMed  CAS  Google Scholar 

  13. El-Beshbishy HA. Aqueous garlic extract attenuates hepatitis and oxidative stress induced by galactosamine/lipopolysaccharide in rats. Phytother Res. 2008;22:1372–1379.

    Article  PubMed  Google Scholar 

  14. Qiu RL, Zhao X, Tang YT, Yu FM, Hu PJ. Antioxidative response to Cd in a newly discovered cadmium hyperaccumulator, Arabis paniculata F. Chemosphere. 2008;74:6–12.

    Article  PubMed  CAS  Google Scholar 

  15. Hayashi Y, Abe M, Murai A, et al. Comparison of effects of nitric oxide synthase (NOS) inhibitors on plasma nitrite/nitrate levels and tissue NOS activity in septic organs. Microbiol Immunol. 2005;49:139–147.

    PubMed  CAS  Google Scholar 

  16. Billiar TR, Curran RD, West MA, Hofmann K, Simmons RL. Kupffer cell cytotoxicity to hepatocytes in coculture requires l-arginine. Arch Surg. 1989;124:1416–1420. Discussion 1420–1411.

    Article  PubMed  CAS  Google Scholar 

  17. Hsieh CH, Frink M, Hsieh YC, et al. The role of MIP-1 alpha in the development of systemic inflammatory response and organ injury following trauma hemorrhage. J Immunol. 2008;181:2806–2812.

    PubMed  CAS  Google Scholar 

  18. Suzuki S, Nakamura S, Serizawa A, et al. Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy. Hepatology. 1996;24:219–225.

    Article  PubMed  CAS  Google Scholar 

  19. Mookerjee RP, Sen S, Davies NA, Hodges SJ, Williams R, Jalan R. Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis. Gut. 2003;52:1182–1187.

    Article  PubMed  CAS  Google Scholar 

  20. Yang BS, Ma YJ, Wang Y, et al. Protective effect and mechanism of stronger neo-minophagen C against fulminant hepatic failure. World J Gastroenterol. 2007;13:462–466.

    PubMed  CAS  Google Scholar 

  21. Li P, Nijhawan D, Budihardjo I, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91:479–489.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by a grant from the Natural Science Foundation of Zhejiang Province, China (Y207464).

Conflict of interest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Ethical approval

The animal protocol in this experiment was approved by the committee of the Tongji University.

Author information

Authors and Affiliations

  1. Department of Gastroenterology, The Tenth Shanghai Hospital, Tongji University, Shanghai, 200072, China

    Jie Lu, Rong Wan, Chuan-Yong Guo & Xing-Peng Wang

  2. Department of Infectious and Liver Disease, First Affiliated Hospital, Whenzhou Medical College, Wenzhou, 23000, China

    Yong-Ping Chen

Authors
  1. Jie Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-Ping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rong Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chuan-Yong Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xing-Peng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xing-Peng Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, J., Chen, YP., Wan, R. et al. Protective Effects of Ulinastatin on Acute Liver Failure Induced by Lipopolysaccharide/d-Galactosamine. Dig Dis Sci 57, 399–404 (2012). https://doi.org/10.1007/s10620-011-1927-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-011-1927-0

Keywords

Search

Navigation