Regular Article
Regenerative Capacities of Normal and Cirrhotic Livers Following 70% Hepatectomy in Rats and the Effect of α-Tocopherol on Cirrhotic Regeneration

https://doi.org/10.1006/jsre.2000.5825Get rights and content

Abstract

Background. The regeneration of normal and cirrhotic liver has been very well demonstrated after partial hepatectomy; although the tissue regenerated by cirrhotic liver is also cirrhotic. The structural differences of the regenerated tissues between normal and cirrhotic livers may also indicate different regeneration capacities. The objective of this study was to compare the regeneration capacities of normal and cirrhotic livers by bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) labeling indices in replicating nuclei and mitotic figures in cells in partially hepatectomized normal and cirrhotic rats and to study the effect of α-tocopherol on cirrhotic liver regeneration.

Methods. Five groups of adult Wistar rats comprised normal livers, cirrhotic livers, regenerated normal livers, regenerated cirrhotic livers, and α-tocopherol-treated regenerated cirrhotic livers. Cirrhosis was induced by intragastric administration of carbon tetrachloride and phenobarbital in the drinking water of the rats. Liver regeneration capacities in normal and cirrhotic rats and following partial hepatectomy in normal and cirrhotic rats and cirrhotic rats that were administered α-tocopherol were evaluated through BrdU incorporation, PCNA labeling, and mitotic indices.

Results. BrdU and PCNA labeling and mitotic indices were zero for normal rats and 4.3 ± 3.5, 6.5 ± 5, and 2.5 ± 1.5 for cirrhotic rats, respectively. The values after partial hepatectomy in normal and cirrhotic rats were 46.2 ± 8.7 and 27.8 ± 7.5 for BrdU labeling, 83.7 ± 6.5 and 51.3 ± 6.8 for PCNA labeling, and 31.8 ± 4.2 and 18.6 ± 3.4 for mitotic index, respectively. For the fifth group comprising cirrhotic rats that were administered α-tocopherol and had undergone partial hepatectomy, BrdU incorporation, PCNA labeling, and mitotic indices were 37.5 ± 6.3, 76.5 ± 6.2, and 27.2 ± 4.2, respectively. When the cirrhotic liver regeneration group was compared with the normal liver regeneration group, rates of liver regeneration in the cirrhotic group were significantly depressed (P < 0.01). Although the BrdU incorporation and PCNA labeling indices of the α-tocopherol-administered cirrhotic liver regeneration group indicated significantly lower rates of liver regeneration when compared with the normal liver regeneration group (P < 0.05), the liver regeneration rates of the α-tocopherol-administered cirrhotic group were also significantly higher than those of the cirrhotic liver regeneration group that was not administered α-tocopherol (P < 0.01).

Conclusions. Cirrhotic livers revealed a significantly depressed capacity for regeneration following partial hepatectomy. α-Tocopherol administration seemed to improve the rates of regeneration in cirrhotic rats with respect to the BrdU incorporation, PCNA labeling, and mitotic indices.

References (36)

  • P.M. Lindroos et al.

    Hepatocyte growth factor rapidly increases in plasma before DNA synthesis and liver regeneration stimulated by partial hepatectomy and carbontetrachloride administration

    Hepatology

    (1991)
  • A.H. Islami et al.

    Regenerative hyperplasia of the cirrhotic liver following partial hepatectomy

    Cancer

    (1958)
  • S. Bengmark et al.

    The influnce of partial hepatectomy in experimental nutritional cirrhosis in the rat

    Acta Chir. Scand.

    (1966)
  • G.K. Michalopoulos et al.

    Liver regeneration

    Science

    (1997)
  • F. Tamura et al.

    Fukumoto, Nakamura, T

    J. Gastroenterol. Hepatol.

    (1998)
  • A. Francavilla et al.

    Hepatic regeneration and growth factors

    J. Surg. Oncol. Suppl.

    (1993)
  • A.C. Selden et al.

    Growth factors and the liver

    Gut

    (1991)
  • Cited by (39)

    • Superparamagnetic iron oxide magnetic nanomaterial-labeled bone marrow mesenchymal stem cells for rat liver repair after hepatectomy

      2014, Journal of Surgical Research
      Citation Excerpt :

      Hepatectomy may induce a number of complications (including intraperitoneal encapsulated fluid, wound infections, bile leakage, postoperative abdominal bleeding, bile impairment, and lung infections), but the most serious one is liver failure, because it is the primary cause of death during the operation or shortly after [16]. In addition, some conditions such as cirrhosis impair the natural regenerative capacity of the liver, further complicating hepatectomy and recovery [17]. Consequently, the use of BMSCs transplantation could improve the postoperative safety of hepatectomy, and reduce complications and deaths.

    • Vitamin E Requirements in Parenteral Nutrition

      2009, Gastroenterology
      Citation Excerpt :

      Low levels of vitamin E and other antioxidants frequently have been detected in patients on PN or as a result of major trauma.78 It has been suggested that depleted levels of vitamin E are associated with increased risk of liver damage caused by major liver surgery.81,82 The function of vitamin E is believed to be mediated by its antioxidant action as a membrane stabilizer.83

    • Serum Endostatin Levels and Regenerative Capacities of Normal and Cirrhotic Livers Following Partial Hepatectomy in Mice: The Response to Different Resection Sizes

      2007, Journal of Surgical Research
      Citation Excerpt :

      This ability is called regeneration. The regeneration of normal and cirrhotic liver has been very well demonstrated after partial hepatectomy [1, 2]. At the cellular level, this process is heralded by the occurrence of active cell division (hyperplasia).

    • Mechanisms of liver fibrosis

      2006, Clinica Chimica Acta
    View all citing articles on Scopus

    This study was performed thanks to support from The Scientific and Technical Research Council of Turkey (TUBITAK).

    2

    To whom correspondence should be addressed. Fax: +90 312 311 55 41. E-mail: [email protected].

    View full text