Chagoya-de-Sánchez V, Suárez-Cuenca JA, Hernández-Muñoz R

Language: Spanish
References: 40
Page: 106-114
PDF size: 600.14 Kb.

ABSTRACT

Cirrhosis is one of the most common causes of mortality worldwide because hepatic dysfunction constitutes a potentially lethal condition. Its etiology is variable and there’s no treatment for prevention or regression of the pathology. But there is an increased risk of sepsis, bacterial peritonitis, variceal bleeding, portal hypertension and development of hepatocellular carcinoma. This document briefly describes the structure and functions of the normal liver in comparison to the cirrhotic liver. Our experience regarding the studies of acute and chronic experimental hepatotoxicity using the nucleoside adenosine as an hepatoprotector is commented. The antifibrogenic effect of this compound increases collagen degradation through decreasing liver TIMPs levels, favoring normalization of liver function mainly by the promotion of hepatocyte proliferation. Comments on important aspects needed to promote the application of these findings in the experimental model to cirrhotic patients are presented as well. Some pharmacological and toxicological studies which lead us to the human use of this compound are also discussed.

REFERENCES

1. Rappaport, A.M. & Wanless, I.R. in Diseases of the liver (ed. Schiff, L. & Schiff, E.R.) (Lippincott Company, Philadelphia, 1993).

2. Laskin, D.L. in Functional heterogeity of liver tissue (ed. Vidal-Vanaclocha, F.) 161-176 (R.G. Landes Company, Austin, 1997).

3. Rescan, P.Y. et al. Distribution and origin of the basement5 membran component perlecan in rat liver and primary hepatocytes culture. Am. J. Pathol. 142, 199-208 (1993).

4. Roskams, T. et al. Heparan sulfate proteoglycan expression in chronic cholestatic human liver disease. Hepatology 24, 524-532 (1992).

5. Rojkind, M., Rojkind, M.H. & Cordero Hernández, J. In vivo collagen synthesis and deposition in fibrotic and regeneration rat livers. Collagen Rel. Res. 3, 335-347 (1983).

6. Rojkind, M. & Mourelle, M. in Collagen (ed. Nimni, M.E. Vol II) (CRC Press Inc., Florida, 1988)

7. Pasternak, C.A. en Bioquímica humana (ed. Barbany Cairó, J.R. & Palés Argulló, S.) 219-224 (EXPAXS, Barcelona,1980).

8. Chagoya, V. en Bioquímica (ed. Herrera, E.) 1183-1194 (Emalsa, 1986).

9. Laënnec, R. in Traité de l’auscultation médicale (ed. Chaude) 193 (Paris, 1826).

10. Conn, H.O. & Atterbury, C.E. in Diseases of the liver (eds. Schiff, L. & Schiff, E.R., 7th ed.) 815-934 (Lippincott, Philadelphia, 1993).

11. Anthony, P.P. et al. The morphology of cirrhosis: Definition, nomenclature and classification. Bull. WHO 55, 521 (1977).

12. Dufour, D.R. et al. Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests. Clin. Chem. 46, 2027-2049 (2000).

13. Pineda-Corona, B.E. Epidemiología de la hepatopatía alcohólica. en enfermedad hepática por alcohol (Encuesta Nacional de Adicciones) 1-5 (1993).

14. Crawford, J.M. in Pathology of the liver (eds. Mac Sween, R.N.M. et al.) 576-577 (Churchill Livingstone, Edinbourch, 2002).

15. Rockey, D.C. Pathophysiology of liver disease. Clinics in Liver Disease 4, 1-36 (2000).

16. Martínez-Hernández, A. & Amenta, P.S. The extracellular matriz in hepatic regeneration. FASEB J. 9, 1401-1410 (1995).

17. Rojkind, M., Giambrone, M.A. & Biempica, L. Collagen types in normal and cirrhotic liver. Gastroenetrology 76, 710-719 (1979).

18. Gressner, A.M. & Bachem, M.G. Molecular mechanism of fibrogenesis a homage to the role of activated fat-storing cells. Digestion 56, 335-346 (1995).

19. Jezequel, A.M. et al. Modulation of extracellular matrix components during dimethynitrosamine-induced cirrhosis. J. Hepatol. 11, 206-214 (1990).

20. Maher, J.J. & McGuire, R.F. Extracellular matrix gene expression increases preferentially in fat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. J. Clin. Invest. 86, 1641-1648 (1990).

21. Van Eyken, P. et al. Localization and cellular sources of the extracellular matrix proteins tenascin in normal and fibrotic rat liver. Hepatology 15, 909-916 (1992).

22. Wyler, D.J. et al. Fibroblast stimulation in schistosomiasis. Egg franuloma macrophages spontaneously secret a fibroblast stimulating factor. J. Immunol. 132, 3142-3148 (1984).

23. Wyler, D.J., Wahl, S.M. & Wahl, L.M. Hepatic fibrosis and schistosomiasis egg granulomas secrete fibroblast stimulating factor in vitro. Science 202, 438-440 (1978).

24. Arthur, M.J.P. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am. J. Physio. Gastrointest. Liver Physiol. 279, G245-G249 (2000).

25. Rojkind, M. & Greenwel, P. in Oxford textbook of clinical hepatology (eds. McIntyre, N., Benhamou, J.P., Bircher, J, Rizzeto, M. & Rode, J.) 375-380 (Oxford Medical Publication, New York, 1991).

26. Chojkier, M. & Brenner, D.A. Therapeutic strategies for hepatic fibrosis. Hepatology 8, 176-182 (1988).

27. Chagoya de Sánchez, V., Brunner, A. & Piña, E. In vivo modification of the energy charge in the liver cell. Biochem. Biophys. Res. Commun. 46, 1441-1445 (1972).

28. Chagoya de Sánchez, V., Brunner, A., Sánchez, M.E., López, C. & Piña, E. Utilization of adenosine as a tool in studies on the regulation of liver glycogen biosynthesis. Arch. Biochem. Biphys. 160, 145-150 (1974).

29. García-Sáinz, J.A., Hernández-Muñoz, R., Santamaría, A. & Chagoya de Sánchez, V. Mechanism of the fatty liver induced by cycloheximide and its reversibility b y adenosine. Biochem. Pharmacol. 28, 1409-1413 (1979).

30. Lautt, W.W., Legare, D.J. & D´Almeida, M.S. Adenosine as putative regulator of hepatic arterial flow (the buffer reponse). Am. J. Physiol. 248, H331-H338 (1985).

31. Hernández-Muñoz, R., Santamaría, A., García-Sainz, J.A., Piña. E. & Chagoya de Sánchez, V. On the mechanism of ethano-induced fatty liver and it reversibility by adenosine. Arch. Biochem. Pharmacol. 190, 155-162 (1978).

32. García-Sainz, J.A., Hernández-Muñoz, R., Glender, W., Piña, E. & Chagoya de Sánchez, V. Effects of adenosine in ethanol-induced modifications of liver metabolism. Role of hepatic redox-state, purine and fatty acid metabolism. Biochem. Pharmacol. 29, 1709-1714 (1980).

33. Hernández-Muñoz, R., Glender, W., Díaz-Muñoz, M., García-Sainz, J.A. & Chagoya de Sánchez, V. Effect of adenosine on liver cell damage induced by carbon tetrachloride. Biochem. Pharmacol. 33, 2599-2604 (1984).

34. Hernández-Muñoz, R., Díaz-Muñoz, M., Suárez, J. & Chagoya de Sánchez, V. Adenosine partially prevents cirrhosis induced b y carbon tetrachloride in rats. Hepatology 12, 242-248 (1990).

35. Hernández-Muñoz, R., Díaz-Muñoz, M. & Chagoya de Sánchez, V. Effects of adenosine administration on the function and membrane composition of liver mitochondria in carbon tetrachloride-induced cirrhosis. Arch. Biochem. Biophys. 294, 160-167 (1992).

36. Hernández-Muñoz, R., Díaz-Muñoz, M. & Chagoya de Sánchez, V. Possible role of cell redeox state on collagen metabolism in carbon tetrachloride induced cirrhosis as evidenced by adenosine administration to rats. Biochi. Biophys. Acta 1200, 93-99 (1994).

37. Hernández-Muñoz, R. & Chagoya de Sánchez, V. In vivo correlation between liver and bloos energy status as evidenced by chronic treatment of carbon tetrachloride and adenosine to rats. Can. J. Physiol. Pharmacol. 72, 1252-1256 (1994).

38. Hernández-Muñoz, R. et al. Balance between oxidative damage and proliferative potential in an experimental model of Ccl4 –induced cirrhosis: protective role of adenosine administration. Hepatology 26, 1100-1110 (1997).

39. Chagoya de Sánchez, V., Díaz-Muñoz, M. & Hernández-Muñoz, R. Reversion of an experimental cirrhosis induced by carbon tetrachloride by adenosine administration. Hepatology 28, 641A (1998).

40. Hernández-Muñoz, R. et al. Adenosine reverses a preestablished CCl4 –induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. Hepatology 34, 677-687 (2001).