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Vinpocetine Ameliorates Acute Hepatic Damage Caused by Administration of Carbon Tetrachloride in Rats

Acta Biologica Hungarica volume 58, pages 411–419 (2007)Cite this article

Abstract

Vinpocetine is a widely used drug for the treatment of cerebrovascular and memory disorders. This study aimed to investigate the effect of vinpocetine on the acute hepatic injury caused in the rat by the administration of CCl4in vivo. Vinpocetine (2.1, 4.2, 8.4 mg/kg) or silymarin (30 mg/kg) was given once daily orally simultaneously with CCl4 and for 15 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Stained sections were subjected to morphometric evaluation using computerized image analyzer. The results showed that vinpocetine administered to CCl4-treated rats decreased the elevated alanine aminotransferase (ALT) by 49.3, 58.1 and 63.6%, aspartate aminotransferase (AST) by 10.5, 22.6 and 27.2% and alkaline phosphatase (ALP) by 52.5, 59.6 and 64.9%, respectively, and in a dose-dependent manner. Meanwhile, silymarin reduced elevated ALT, AST and ALP levels by 53.1, 26.9 and 66%, respectively. Histological examination of liver specimens revealed a marked reduction in liver cell necrosis in vinpocetine and silymarin-treated rats compared with vehicle-treated CCl4-treated rats. Quantitative analysis of the area of damage showed 85.3% reduction in the area of damage after silymarin and 72.2, 78.9 and 82.6% reduction after vinpocetine treatment at 2.1, 4.2, 8.4 mg/kg, respectively. It is concluded that administration of vinpocetine in a model of CCl4-induced liver injury in rats reduced liver damage. The reduction obtained by 4.2 mg/kg of vinpocetine was similar to that obtained by 30 mg/kg silymarin. Therefore, it is suggested that vinpocetine might be a good pharmacological agent in the treatment of liver disease besides its neuroprotective effects.

References

  1. 1.

    Arif, A., Levine, R. A., Sanderson, S. O., Bank, L., Velu, R. P., Shah, A., Mahl, T. C., Gregory, D. H. (2003) Regression of fibrosis in chronic hepatitis C after therapy with interferon and ribavirin. Dig. Dis. Sci. 48, 1425–1430.

    CAS  Article  Google Scholar 

  2. 2.

    Bacon, B. R. (2004) Managing hepatitis C. Am. J. Manag. Care 10, S30-S40.

  3. 3.

    Bauer, J. D. (1982) Clinical Laboratory Methods. The C. V. Mosby Co., St. Louis, Toronto, London.

    Google Scholar 

  4. 4.

    Bedossa, R. (1999) Natural history of liver fibrosis. Adv. Liver. Pathol. 32, 292–293.

    Google Scholar 

  5. 5.

    Belfield, A., Goldberg, D. M. (1971) Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme 12, 561–573.

    CAS  Article  Google Scholar 

  6. 6.

    Bonoczk, P., Gulyas, B., Adam-Vizi, V., Nemes, A., Karpati, E., Kiss, B., Kapas, M., Szantay, C., Koncz, I., Zelles, T., Vas, A. (2000) Role of sodium channel inhibition in neuroprotection: effect of vinpocetine. Brain Res. Bull. 53, 245–254.

    CAS  Article  Google Scholar 

  7. 7.

    Crowley, L. V. (1967) The Reitman-Frankel colorimetric transaminase procedure in suspected myocardial infarction. Clin. Chem. 13, 482–487.

    CAS  PubMed  Google Scholar 

  8. 8.

    Farghali, H., Kamenikova, L., Hynie, S., Kmonickova, E. (2000) Silymarin effects on intracellular calcuim and cytotoxicity: a study in perfused rat hepatocytes after oxidative stress injury. Pharmacol. Res. 41, 231–237.

    CAS  Article  Google Scholar 

  9. 9.

    Flora, K., Hahn, M., Rosen, H., Benner, K. (1998) Milk thistle (Silybum marianum) for the therapy of liver disease. Am. J. Gastroenterol. 93, 139–143.

    CAS  Article  Google Scholar 

  10. 10.

    Fried, M. W. (2002) Side effects of therapy of hepatitis C and their management. Hepatology 36, S237–S244.

    PubMed  Google Scholar 

  11. 11.

    Hadjiev, D. (2003) Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine. Ideggyógy. Szemle 56, 166–172.

    PubMed  Google Scholar 

  12. 12.

    Hsu, C. T., Schichijo, K., Ito, M., Sekine, I. (1993) The effect of chemical sympathectomy on acute liver injury induced by carbon tetrachloride in spontaneously hypertensive rats. J. Auton. Nerv. Syst. 43, 91–96.

    CAS  Article  Google Scholar 

  13. 13.

    Kiss, B., Karpati, E. (1996) A blockade of Na (+) channels can prevent some of the mechanisms involved in CCl4 induced hepatotoxicity. Acta Pharm. Hung. 66, 213–224.

    CAS  PubMed  Google Scholar 

  14. 14.

    Landon, E. J., Naukam, R. J., Rama-Sastry, B. V. (1986) Effects of calcium channel blocking agents on calcium and centrilobular necrosis in the liver of rats treated with hepatotoxic agents. Biochem. Pharmacol. 35, 697–705.

    CAS  Article  Google Scholar 

  15. 15.

    Lillestll, I. K., Helle, K. B., Aardal, S. (1998) Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long-lasting contraction to endothelin-1 in the porcine coronary artery. Scand. J. Clin. Lab. Invest. 58, 625–634.

    CAS  Article  Google Scholar 

  16. 16.

    Maher, J. J. (2001) Interactions between hepatic stellate cells and the immune system. Semin. Liver Dis. 21, 417–426.

    CAS  Article  Google Scholar 

  17. 17.

    Manns, M. P., McHutchison, J. G., Gordon, S. C. et al. (2001) Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358, 958–965.

    CAS  Article  Google Scholar 

  18. 18.

    Marcellin, P., Asselah, T., Boyer, N. (2002) Fibrosis and disease progression in hepatitis C. Hepatology 36, S47-56.

  19. 19.

    McCaughan, G. W., George, J. (2004) Fibrosis progression in chronic hepatitis C virus infection. Gut 53, 318–321.

    CAS  Article  Google Scholar 

  20. 20

    Muriel, P., Mourelle, M. (1990) Prevention by silymarin of membrane alterations in acute CCl4 liver damage. J. Appl. Toxicol. 10, 275–279.

    CAS  Article  Google Scholar 

  21. 21.

    Nekrassov, V., Sitges, M. (2000) Vinpocetine protects from aminoglycoside antibiotic-induced hearing loss in guinea pig in vivo. Brain. Res. 868, 222–229.

    CAS  Article  Google Scholar 

  22. 22.

    Paget, G. E., Barnes, J. M. (1964) In: Laurence, D. R., Bacharach, A. L. (eds) Evaluation of Drug Activities Pharmacometics. Academic Press, London & NewYork, pp. 1–135.

  23. 23.

    Pianko, S., McHutchison, J. G. (2000) Treatment of hepatitis C with interferon and ribavirin. J. Gastroenterol. Hepatol. 15, 581–586.

    CAS  Article  Google Scholar 

  24. 24.

    Romero, G., Lasheras, B., Sainz-Suberviola, L., Cenarruzabeitia, E. (1994) Protective effects of calcium channel blockers in carbon tetrachloride-induced liver toxicity. Life Sci. 55, 981–990.

    CAS  Article  Google Scholar 

  25. 25.

    Sippel, H., Stauffert, I., Estler, C. J. (1993) Protective effect of various calcium antagonists against an experimentally induced calcium overload in isolated hepatocytes. Biochem. Pharmacol. 46, 1937–1944.

    CAS  Article  Google Scholar 

  26. 26.

    Sitges, M., Galvan, E., Nekrassov, V. (2005) Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes. Neurochem. Int. 46, 533–540.

    CAS  Article  Google Scholar 

  27. 27.

    Tanaka, N., Tanaka, K., Nagashima, Y., Kondo, M., Sekihara, H. (1999) Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride-induced acute hepatic injury. Gastroenterology 117, 173–180.

    CAS  Article  Google Scholar 

  28. 28.

    Szakács, T., Veres, Zs., Vereczkey, L. (2001) In vitro-in vivo correlation of the pharmakokinetics of vinpocetine. Pol. J. Pharmacol. 53, 623–628.

    PubMed  Google Scholar 

  29. 29.

    Vas, A., Gulyas, B., Szabo, Z., Bonoczk, P., Csiba, L., Kiss, B., Karpati, E., Panczel, G., Nagy, Z. (2002) Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences. J. Neurol. Sci. 203–204, 259–262.

    Article  Google Scholar 

  30. 30.

    Wellington, K., Jarvis, B. (2001) Silymarin: a review of its clinical properties in the management of hepatic disorders. BioDrugs 15, 465–489.

    CAS  Article  Google Scholar 

  31. 31.

    Wu, S. N. (2003) Large-conductance Ca2+-activated K+ channels: physiological role and pharmacology. Curr. Med. Chem. 10, 649–661.

    CAS  Article  Google Scholar 

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Affiliations

  1. Department of Pharmacology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    O. M. E. Abdel Salam

  2. Department of Medical Biochemistry, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Fatma Hassan Oraby

  3. Department of Pathology, National Research Centre, Tahrir St., Dokki, Cairo, Egypt

    Nabila S. Hassan

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  1. O. M. E. Abdel Salam
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  2. Fatma Hassan Oraby
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  3. Nabila S. Hassan
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Correspondence to O. M. E. Abdel Salam.

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Abdel Salam, O.M.E., Oraby, F.H. & Hassan, N.S. Vinpocetine Ameliorates Acute Hepatic Damage Caused by Administration of Carbon Tetrachloride in Rats. BIOLOGIA FUTURA 58, 411–419 (2007). https://doi.org/10.1556/ABiol.58.2007.4.8

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Keywords

  • Vinpocetine
  • silymarin
  • carbon tetrachloride
  • rat
  • liver injury