Skip to main content
Log in

Endocannabinoids anandamide and its cannabinoid receptors in liver fibrosis after murine schistosomiasis

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

This study examined endogenous cannabinoid (ECB)-anandamide (AEA) and its cannabinoid receptors (CBR) in mice liver with the development of schistosoma japonicum. Mice were infected with schistosoma by means of pasting the cercaria onto their abdomens. Liver fibrosis was pathologically confirmed nine weeks after the infection. High performance liquid chromatography (HPLC) was employed to determine the concentration of AEA in the plasma of mice. Immunofluorescence was used to detect the expression of CBR1 and CBR2 in liver tissue. Morphological examination showed typical pathological changes, with worm tubercles of schistosoma deposited in the liver tissue, fibrosis around the worm tubercles and infiltration or soakage of inflammatory cells. Also, CBR1 and CBR2 were present in hepatocytes and hepatic sinusoids of the two groups, but they were obviously enhanced in the schistosoma-infected mice. However, the average optical density of CBR1 in the negative control and fibrosis group was 13.28±7.32 and 30.55±7.78, and CBR2 were 28.13±6.42 and 52.29±4.24 (P<0.05). The levels of AEA in the fibrosis group were significantly increased as compared with those of the control group. The concentrations of AEA were (0.37±0.07) and (5.67±1.34) ng/mL (P<0.05). It is concluded that the expression of endocannabinoids AEA and its cannabinoid receptor CBR were significantly increased in schistosoma-infected mice. Endogenous endocannabinoids may be involved in the development of schistosoma-induced liver fibrosis.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Utzinger J, Zhou XN, Chen MG, et al. Conquering schistosomiasis in China: the long march. Acta Trop, 2005, 96(2–3):69–96

    PubMed  Google Scholar 

  2. Zhou XN, Wang LY, Chen MG, et al. The public health significance and control of schistosomiasis in China — then and now. Acta Trop, 2005,96(2–3):97–105

    Article  PubMed  Google Scholar 

  3. Manzella A, Ohtomo K, Monzawa S, et al. Schistosomiasis of the liver. Abdom Imaging, 2008,33(2):144–150

    Article  PubMed  Google Scholar 

  4. Jia TW, Zhou XN, Wang XH, et al. Assessment of the age-specific disability weight of chronic schistosomiasis japonica. Bull World Health Organ, 2007,85(6):458–465

    Article  PubMed  Google Scholar 

  5. Chen H, He YW, Liu WQ, et al. Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum. World J Gastroenterol, 2008,14(18):2905–2911

    Article  PubMed  CAS  Google Scholar 

  6. Jimenez W. Endocannabinoids and liver disease. Hepatology, 2005,41(5):983–985

    Article  PubMed  CAS  Google Scholar 

  7. Moezi L, Gaskari SA, Lee SS. Endocannabinoids and liver disease. V. endocannabinoids as mediators of vascular and cardiac abnormalities in cirrhosis. Am J Physiol Gastrointest Liver Physiol, 2008,295(4):649–653

    Article  CAS  Google Scholar 

  8. Julien B, Grenard P, Teixeira-Clerc F, et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology, 2005,128(3):742–755

    Article  PubMed  CAS  Google Scholar 

  9. Teixeira-Clerc F, Julien B, Grenard P, et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med, 2006,12(6):671–676

    Article  PubMed  CAS  Google Scholar 

  10. Maccarrone M, Finazzi-Agro A. The endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis. Cell Death Differ, 2003,10(9):946–955

    Article  PubMed  CAS  Google Scholar 

  11. Sarker KP, Maruyama I. Anandamide induces cell death independently of cannabinoid receptors or vanilloid receptor 1: possible involvement of lipid rafts. Cell Mol Life Sci, 2003,60(6): 1200–1208

    PubMed  CAS  Google Scholar 

  12. Siegmund SV, Uchinami H, Osawa Y, et al. Anandamide induces necrosis in primary hepatic stellate cells. Hepatology, 2005,41(5):1085–1095

    Article  PubMed  CAS  Google Scholar 

  13. Liu HY, Yang Q, Duan RX, et al. Effects of anandamide on the activation and proliferation of hepatic stellate cells through cannabinoid-2 receptors. Zhonghua Gan Zang Bing Za Zhi (Chinese), 2008,16(6):430–434

    CAS  Google Scholar 

  14. Mallat A, Loterszatjn S. Endocananbinoids as novel mediators of liver disease. J Endocrinol Invest, 2006, 29(suppl 3):58–65

    PubMed  CAS  Google Scholar 

  15. Batkai S, Wagner JA, Goparaju SK, et al. Endocanabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat Med, 2001, 7(7):827–832

    Article  PubMed  CAS  Google Scholar 

  16. Schmidt A, Brune K, Hinz B. Determination of the endocannabinoid anandamide in human plasma by high-performance liquid chromatography. Biomed Chromatogr, 2006,20(4):336–342

    Article  PubMed  CAS  Google Scholar 

  17. Koga D, Santa T, Hagiwara K, et al. High-performance liquid chromatography and fluorometric detection of arachidonylethanolamide (anandamide) and its analogues, derivatized with 4-(N-chloroformylmethyl-N-methyl) amino-7-N, N-dimethylaminosulp honyl-2, 1, 3-benzoxadiazole (DBD-COCl). Biomed Chromatogr, 1995, 9(1):56–57

    Article  PubMed  CAS  Google Scholar 

  18. Di Marzo V, Bifulco M, Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov, 2004,3(9):771–784

    Article  PubMed  CAS  Google Scholar 

  19. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 1992,258(5090):1946–1949

    Article  PubMed  CAS  Google Scholar 

  20. Mechoulam R, Panikashvili D, Shohami E. Cannabinoids and brain injury: therapeutic implications. Trends Mol Med, 2002,8(2):58–61

    Article  PubMed  CAS  Google Scholar 

  21. Maccarrone M, Finazzi-Agro A. Endocannabinoids and their actions. Vitam Horm, 2002,65:225–255

    Article  PubMed  CAS  Google Scholar 

  22. Lynn AB, Herkenham M. Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther, 1994,268(3):1612–1623

    PubMed  CAS  Google Scholar 

  23. De Filippis D, D’Amico A, Iuvone T. Cannabinomimetic control of mast cell mediator release: new perspective in chronic inflammation. J Neuroendocrinol, 2008,20(Suppl 1):20–25

    Article  PubMed  CAS  Google Scholar 

  24. Pacher P, Gao B. Endocannabinoids and liver disease. III. Endocannabinoid effects on immune cells: implications for inflammatory liver diseases. Am J Physiol Gastrointest Liver Physiol, 2008,294(4):850–854

    Article  CAS  Google Scholar 

  25. Siegmund SV, Schwabe RF. Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am J Physiol Gastrointest Liver Physiol, 2008,294(2):357–362

    Article  CAS  Google Scholar 

  26. Teixeira-Clerc F, Julien B, Grenard P, et al. The endocannabinoid system as a novel target for the treatment of liver fibrosis. Pathol Biol (Paris), 2008,56(1):36–38

    CAS  Google Scholar 

  27. Osei-Hyiaman D, DePetrillo M, Pacher P, et al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest, 2005,115(5):1298–1305

    PubMed  CAS  Google Scholar 

  28. Biswas KK, Abeyama K, Kawahara K, et al. Membrane cholesterol but not putative receptors mediates anandamide-induced hepatocyte apoptosis. Hepatology, 2003, 38(5):1167–1177

    Article  PubMed  CAS  Google Scholar 

  29. Ros J, Claria J, To-Figueras J, et al. Endogenous cannabinoids: a new system involved in the homeostasis of arterial pressure in experimental cirrhosis in the rat. Gastroenterology, 2002,122(1):85–93

    Article  PubMed  CAS  Google Scholar 

  30. Lotersztajn S, Teixeira-Clerc F, Hezode C, et al. Endocannabinoids: therapeutic perspectives in chronic liver diseases. Gastroenterol Clin Biol, 2007,31(3):255–258

    Article  PubMed  CAS  Google Scholar 

  31. Lotersztajn S, Teixeira-Clerc F, Julien B, et al. CB2 receptors as new therapeutic targets for liver diseases. Br J Pharmacol, 2008,153(2):286–289

    Article  PubMed  CAS  Google Scholar 

  32. Batkai S, Osei-Hyiaman D, Pan H, et al. Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J, 2007,21(8):1788–1800

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This project was supported by a grant from the National Natural Sciences Foundation of China (No. 30571627).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, H., Gao, X., Duan, R. et al. Endocannabinoids anandamide and its cannabinoid receptors in liver fibrosis after murine schistosomiasis. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 182–186 (2009). https://doi.org/10.1007/s11596-009-0209-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-009-0209-y

Key words

Navigation