Skip to main content
Log in

Protection Against Microcystin-LR-Induced Hepatotoxicity by Silymarin: Biochemistry, Histopathology, and Lethality

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Microcystin-LR, a cyclic heptapeptide synthesized by the blue-green algae, Microcystis aeruginosa, is a potent hepatotoxin. Pathological examination of livers from mice and rats that received microcystin-LR revealed severe, peracute, diffuse, centrilobular hepatocellular necrosis, and hemorrhage. These changes were correlated with increased serum activities of sorbitol dehydrogenase, alanine aminotransferase, and lactate dehydrogenase. Pretreatment of either rats or mice with a single dose of silymarin, a flavonolignane isolated from the wild artichoke (Silybum marianum L. Gaertn), completely abolished the lethal effects, pathological changes, and significantly decreased the levels of serum enzymes induced by microcystin-LR intoxication.

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. D. P. Botes, A. A. Tuinman, P. L. Wessels, C. C. Viljoen, H. Kruger, D. H. Williams, S. Santikarn, R. J. Smith, and S. J. Hammond. The structure of cyanoginosin-LA, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa. J. Chem. Soc. Perkin Trans. 1:2311–2318 (1984).

    Google Scholar 

  2. M. T. Runnegar and I. R. Falconer. Effect of toxin from the cyanobacterium Microcystis aeruginosa on ultrastructural morphology and actin polymerization in isolated hepatocytes. Toxicon 24:109–115 (1986).

    Google Scholar 

  3. D. N. Slatkin, R. D. Stoner, W. H. Adams, J. H. Kycia, and H. W. Siegelman. Atypical pulmonary thrombosis caused by a toxic peptide. Science 220:1383–1385 (1983).

    Google Scholar 

  4. G. A. Miura, N. A. Robinson, T. W. Geisbert, K. A. Bostian, J. D. White, and J. G. Pace. Comparison of in vivo and in vitro toxic effects of microcystin-LR in fasted rats. Toxicon 27:1229–1240 (1989).

    Google Scholar 

  5. W. H. Adams, R. D. Stoner, D. G. Adams, D. N. Slatkin, and H. W. Siegelman. Pathophysiologic effects of a toxic peptide from Microcystis aeruginosa. Toxicon 23:441–447 (1985).

    Google Scholar 

  6. A. Pelter and R. Hansel. The structure of silybin (silybim substance E6, the first flavonolignan. Tetrahedron Lett. 25:2911–2916 (1968).

    Google Scholar 

  7. G. Hahn, H. D. Lehmann, M. Kurten, H. Uebel, and G. Vogel. Pharmacology and toxicology of silymarin, the anti-hepatotoxic mechanism of Silybum marianum (L.) Gaertn. Arzneim Forsch. 23:698–704 (1973).

    Google Scholar 

  8. K. A. Mereish and R. Solow. Effect of antihepatotoxic agents against microcystin-LR toxicity in cultured rat hepatocytes. Pharm. Res. 7:256–259 (1990).

    Google Scholar 

  9. G. W. Parker and D. G. Martin. Technique for cardiovascular monitoring in awake tethered rats. Lab. Anim. Sci. 39:463–467 (1989).

    Google Scholar 

  10. A. Valenzuela, C. Lagos, K. Schmidt, and L. A. Videla. Silymarin protection against hepatic lipid peroxidation induced by acute ethanol intoxication in the rat. Biochem. Pharmacol. 34:2209–2212 (1985).

    Google Scholar 

  11. J. Baumann, F. von Bruchhausen, and G. Wurm. Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation. Prostaglandins 20:627–639 (1980).

    Google Scholar 

  12. A. Valenzuela and R. Guerra. Differential effect of silybin on the Fe+2-ADP and t-butylhydroperoxide-induced microsomal lipid peroxidation. Experientia 42:139–141 (1986).

    Google Scholar 

  13. A. Valenzuela, R. Guerra, and L. A. Videla. Antioxidant properties of the flavonoids silybin and (+)-cyanodanol-3: comparison with butylated hydroxyanisole and butylated hydroxytoluene. Planta Med. 6:438–440 (1986).

    Google Scholar 

  14. J. Sonnenbichler and I. Zetl. Biochemical effects of the flavonolignane silibinin on RNA, protein and DNA synthesis in rat livers. Prog. Clin. Biol. Res. 213:319–331 (1986).

    Google Scholar 

  15. I. R. Falconer and M. T. Runnegar. Effect of the peptide toxin from Microcystis aeruginosa on intracellular calcium, pH and membrane integrity in mammalian cells. Chem. Biol. Interact. 63:215–225 (1987).

    Google Scholar 

  16. M. T. Runnegar, J. Andrews, R. G. Gerdes, and I. R. Falconer. Injury to hepatocytes induced by a peptide toxin from the cyanobactrium Microcystis aeruginosa. Toxicon 25:1235–1239 (1987).

    Google Scholar 

  17. S. M. Naseem, H. B. Hines, D. A. Creasia, and K. A. Mereish. Comparative effect of toxins on arachidonic acid release and metabolism in cultured rat hepatocytes and alveolar macrophages. Fed. Am. Soc. Exp. Biol. J. 2:A1353 (1988).

    Google Scholar 

  18. W. H. Adams, J. P. Stone, B. Sylvester, R. D. Stoner, D. N. Slatkin, N. R. Tempel, and H. W. Siegelman. Pathophysiology of cyanoginosin-LR: In vivo and in vitro studies. Toxicol. Appl. Pharmacol. 96:248–257 (1988).

    Google Scholar 

  19. M. T. Runnegar, I. R. Falconer, and J. Silver. Deformation of isolated rat hepatocytes by a peptide hepatotoxin from the blue-green alga Microcystis aeruginosa. Naunyn-Schmiedeberg Arch. Pharmacol. 317:268–272 (1981).

    Google Scholar 

  20. S. B. Hooser, V. R. Beasley, R. A. Lovell, W. W. Carmichael, and W. M. Haschek. Toxicity of microcystin-LR, a cyclic heptapeptide hepatotoxin from Microcystis aeruginosa to rats and mice. Vet. Pathol. 26:246–252 (1989).

    Google Scholar 

  21. F. Mirabelli, A. Salis, V. Marinoni, G. Finardi, G. Bellomo, H. Thor, and S. Orrenius. Menadione-induced bleb formation in hepatocytes is associated with the oxidation of thiol groups in actin. Arch. Biochem. Biophys. 264:261–269 (1988).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mereish, K.A., Bunner, D.L., Ragland, D.R. et al. Protection Against Microcystin-LR-Induced Hepatotoxicity by Silymarin: Biochemistry, Histopathology, and Lethality. Pharm Res 8, 273–277 (1991). https://doi.org/10.1023/A:1015868809990

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015868809990

Navigation