Skip to main content
Log in

Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

In liver cirrhosis, liver tissue becomes progressively substituted by fibrosis, ultimately leading to architectural distortion, liver circulatory changes, and liver failure. Some data support the hypothesis that protein undernutrition may play a role in the development and progression of nonalcoholic liver cirrhosis and that this progression is at least partially mediated by changes in glutathione peroxidase (GPX), superoxide dismutase (SOD), and other antioxidative systems, leading to an increase in lipid peroxidation. We analyzed the effects of protein deficiency on liver Cu, Fe, Zn, Mn, and Se in carbon tetrachloride (CCl4)-induced liver cirrhosis, the relation of protein undernutrition and these trace elements with the activity of some hepatic antioxidative enzymatic mechanisms, and the relation of all of them with morphological and biochemical changes in 40 male adult Sprague-Dawley rats divided in four groups. Liver cirrhosis was induced by intraperitoneal injection of CCl4 to 10 rats fed a 2% protein diet and another 10 fed a 18% protein control diet; two further groups included rats without cirrhosis fed the 2% protein and the 18% protein diets. The study period lasted 6 wk. GPX, SOD, and lipid peroxidation products as well as Zn, Cu, Mn, Se, and Fe were determined in liver samples. We found that liver GPX and Se were reduced in the cirrhotic animals, especially in the low-protein-fed ones, protein deficiency, but not cirrhosis, exerting the main effects. A close correlation was found between liver GPX and serum albumin and weight loss and an inverse one among GPX and hepatocyte ballooning, liver fibrosis, and fat, histomorphometrically determined. These results suggest a pathogenetic role of decreased GPX in the progression of liver disease, which may become enhanced by concomitant protein undernutrition. In addition to iron, the levels of which were increased in the malnourished rats, no differences were found regarding the other trace elements, SOD activity, and lipid peroxidation products.

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. C. S. Lieber, Alcohol, protein metabolism, and liver injury, Gastroenterology 79, 373–390 (1980).

    PubMed  CAS  Google Scholar 

  2. C. S. Lieber, Alcohol and fibrogenesis, Alcohol Alcohol. 1991(Suppl. 1), 339–344 (1991).

    Google Scholar 

  3. C. S. Lieber, Ethanol metabolism, cirrhosis and alcoholism, Clin. Chim. Acta 257, 59–84 (1997).

    Article  PubMed  CAS  Google Scholar 

  4. I. Sternlieb, Copper and the liver, Gastroenterology 78, 1615–1628 (1980).

    PubMed  CAS  Google Scholar 

  5. S. Rana, C. P. Sodhi, K. Vaiphei, et al., Protein-energy malnutrition and oxidative injury in growing rats, Hum. Exp. Toxicol. 15, 810–814 (1996).

    Article  PubMed  CAS  Google Scholar 

  6. H. Lenhartz, R. Ndasi, A. Anninos, et al., The clinical manifestation of the kwashiorkor syndrome is related to increased lipid peroxidation, J. Pediatr. 132, 879–881 (1998).

    Article  PubMed  CAS  Google Scholar 

  7. M. M. Tatli, H. Vural, A. Koc, et al., Altered anti-oxidant status and increased lipid peroxidation in marasmic children, Pediatr. Int. 42, 289–292 (2000).

    Article  PubMed  CAS  Google Scholar 

  8. I. Grattagiano, G. Vendemiale, P. Caraceni, et al., Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet, J. Nutr. 130, 2131–2136 (2000).

    Google Scholar 

  9. J. Beltowski, G. Wojcicka, D. Gorny, et al., The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity, J. Physiol. Pharmacol. 51, 883–896 (2000).

    PubMed  CAS  Google Scholar 

  10. A. Bosma, W. F. Seifert, C. G. Van Thiel de Ruiter, et al., Alcohol in combination with malnutrition causes increased liver fibrosis in rats, J. Hepatol. 21, 394–402 (1994).

    Article  PubMed  CAS  Google Scholar 

  11. A. Conde-Martel, E. González-Reimers, F. Santolaria-Fernández, et al., Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents, Alcohol 9, 341–348 (1992).

    Article  PubMed  CAS  Google Scholar 

  12. M. Gasso, M. Rubio, G. Varela, et al., Effects of S adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis, J. Hepatol. 25, 200–205 (1996).

    Article  PubMed  CAS  Google Scholar 

  13. B. M. Dworkin, W. S. Rosenthal, R. E. Stahl, et al., Decreased hepatic selenium content in alcoholic cirrhosis, Dig. Dis. Sci. 33, 1213–1217 (1988).

    Article  PubMed  CAS  Google Scholar 

  14. U. Johansson, F. Johansson, B. Joelsson, et al., Selenium status in patients with liver cirrhosis and alcoholism, Br. J. Nutr. 55, 227–233 (1986).

    Article  PubMed  CAS  Google Scholar 

  15. M. Rojind and M. A. Dunn, Hepatic fibrosis, Gastroenetrology 76, 846–863 (1979).

    Google Scholar 

  16. R. W. Chapman, M. Y. Morgan, M. Laulicht, et al., Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic haemochromatosis, Dig. Dis. Sci. 27, 909–916 (1982).

    Article  PubMed  CAS  Google Scholar 

  17. P. Brissot, J. P. Campion, A. Guillouzo, et al., Experimental hepatic iron overload in the baboon: results of a two-year study. Evolution of biological and morphological hepatic parameters of iron overload, Dig. Dis. Sci. 28, 616–624 (1983).

    Article  PubMed  CAS  Google Scholar 

  18. P. Brissot, J. Farjanel, D. Bourel, et al., Chronic liver iron overload in the baboon by ferric nitrilotriacetate: morphologic and functional changes with special reference to collagen synthesis enzymes, Dig. Dis. Sci. 32, 620–627 (1987).

    Article  PubMed  CAS  Google Scholar 

  19. B. R. Bacon, A. S. Tyavill, G. M. Brittenham, et al., Hepatic lipid peroxidation in vivo in rats with chronic iron overload, J. Clin. Invest. 71, 429–439 (1983).

    Article  PubMed  CAS  Google Scholar 

  20. G. Minotti and S. D. Aust SD, The requirement for iron III in the initiation of lipid peroxidation by iron II and hydrogen peroxide, J. Biol. Chem. 262, 1098–1104 (1987).

    PubMed  CAS  Google Scholar 

  21. A. A. Jackson, Severe undernutrition in Jamaica, Acta Paediatr. Scand. 323, 43–51 (1986).

    CAS  Google Scholar 

  22. E. González-Reimers, A. Martínez Riera, F. Santolaria-Fernández, et al., Relative and combined effects of ethanol and protein deficiency on zinc, iron, copper, and manganese contents in different organs and urinary and fecal excretion, Alcohol 16, 7–12 (1998).

    Article  PubMed  Google Scholar 

  23. C. S. Lieber, L. M. De Carli, and M. Sorrell, Experimental methods of ethanol administration, Hepatology 10, 501–510 (1989).

    Article  PubMed  CAS  Google Scholar 

  24. E. J. Underwood, Trace Elements in Human and Animal Nutrition, Academic, New York (1977).

    Google Scholar 

  25. H. Shimizu, K. Uetsuka, H. Nakayama, et al., Carbon tetrachloride-induced acute liver injury in Mini and Wistar rats, Exp. Toxicol. Pathol. 53, 11–17 (2001).

    Article  PubMed  CAS  Google Scholar 

  26. E. González-Reimers, A. Castañeyra-Perdomo, F. Santolaria-Fernández, et al., Effect of ethanol on liver cell development in the male albino mouse, Drug Alcohol Depend. 19, 35–44 (1987).

    Article  PubMed  Google Scholar 

  27. H. E. Ganther, D. G. Hafeman, R. A. Lawrence, et al., Selenium and glutathione peroxidase in health and disease, in Trace Elements in Health and Disease, A. S. Prasad and D. Oberleas, Academic, New York, pp. 165–234 (1976).

    Google Scholar 

  28. J. Aaseth, J. Alexander, Y. Thomassen, et al., Serum selenium levels in liver diseases, Clin. Biochem. 15, 281–283 (1982).

    Article  PubMed  CAS  Google Scholar 

  29. R. F. Burk, D. S. Early, K. E. Hill, et al., Plasma selenium in patients with cirrhosis, Hepatology 27, 794–798 (1998).

    Article  PubMed  CAS  Google Scholar 

  30. M. J. Valimaki, K. J. Harju, and R. H. Ylikahri, Decreased serum selenium in alcoholic—a consequence of liver dysfunction, Clin. Chim. Acta 130, 291–296 (1983).

    Article  PubMed  CAS  Google Scholar 

  31. J. Aaseth, A. Smith-Kielland, and Y. Thomassen, Selenium, alcohol and liver diseases, Ann. Clin. Res. 18, 43–47 (1986).

    PubMed  CAS  Google Scholar 

  32. H. Korpela, J. Kumpulainen, P. V. Luoma, et al., Decreased serum selenium in alcoholics are related to liver structure and function, Am. J. Clin. Nutr. 42, 147–151 (1985).

    PubMed  CAS  Google Scholar 

  33. P. J. Tuluvath and D. R. Triger, Selenium in chronic liver disease, J. Hepatol. 14, 176–182 (1992).

    Article  Google Scholar 

  34. M. Casaril, A. M. Stanzial, G. B. Gabrielli, et al., Serum selenium in liver cirrhosis: correlation with markers of fibrosis, Clin. Chim. Acta 182, 221–227 (1989).

    Article  PubMed  CAS  Google Scholar 

  35. A. Van Gossum and J. Neve, Low selenium status in alcoholic cirrhosis is correlated with aminopyrine breath test. Preliminary effects of selenium supplementation, Biol. Trace Element Res. 47, 201–207 (1995).

    Google Scholar 

  36. C. Loguercio, V. De Girolamo, A. Federico, et al., Trace elements and chronic liver disease, Trace Elements Med. Biol. 11, 158–161 (1997).

    CAS  Google Scholar 

  37. H. S. Lee and A. S. Csallany, The influence of vitamin E and selenium on lipid peroxidation and aldehyde dehydrogenase activity in rat liver and tissue, Lipids 29, 345–350 (1994).

    Article  PubMed  CAS  Google Scholar 

  38. J. Camps, T. Bargallo, A. Giménez, et al., Relationship between hepatic lipid peroxidation and fibrogenesis in carbon-tetrachloride-treated rats: effect of zinc administration, Clin. Sci. (Lond.) 83, 695–700 (1992).

    CAS  Google Scholar 

  39. H. Anttinnen, L. Ryhänen, U. Puistola, et al., Decrease in liver collagen accumulation in carbon tetrachloride injured and normal growing rats upon administration of zinc, Gastroenterology 86, 532–539 (1984).

    Google Scholar 

  40. E. Gaudio, L. Pannarale, A. Franchitto, et al., Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study, Int. J. Exp. Pathol. 74, 463–469 (1993).

    PubMed  CAS  Google Scholar 

  41. M. Cabré, J. Camps, J. L. Paternain, et al., Time-course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon-tetrachloride-induced cirrhosis, Clin. Exp. Pharmacol. Physiol. 27, 694–699 (2000).

    Article  PubMed  Google Scholar 

  42. M. Cabré, N. Ferré, J. Folch, et al., Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats, Hepatology 31, 228–234 (1999).

    Article  Google Scholar 

  43. J. M. Hsu, Biochemistry and metabolims of Zinc, in Zinc and Copper in Medicine, Z. A. Karcioglu and R. M. Sarper, eds., Charles C Thomas, Springfield, IL, pp. 66–93 (1980).

    Google Scholar 

  44. A. Conde-Martel, E. González-Reimers, F. Santolaria-Fernández, et al., Cambios hepáticos en la malnutrición proteica: estudio experimental en ratas, Nutr Hosp 8, 358–363 (1993).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

González-Reimers, E., López-Lirola, A., Martín Olivera, R. et al. Effects of protein deficiency on liver trace elements and antioxidant activity in carbon tetrachloride-induced liver cirrhosis. Biol Trace Elem Res 93, 127–139 (2003). https://doi.org/10.1385/BTER:93:1-3:127

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/BTER:93:1-3:127

Index Entries

Navigation