Platelet increases survival in a model of 90% hepatectomy in rats

Liver Int. 2014 Aug;34(7):1049-56. doi: 10.1111/liv.12326. Epub 2013 Oct 1.

Abstract

Background & aims: Ninety per cent hepatectomy in rodents is a model for acute liver failure. It has been reported that platelets have a strong effect enhancing liver regeneration, because of the production of several growth factors such as serotonin. The aim of this study was to investigate the role of microencapsulated platelets on 90% hepatectomy in rats.

Methods: Platelets (PLT) were microencapsulated in sodium alginate and implanted in the peritoneum of rats after 90% partial hepatectomy (PH). Control group received empty capsules (EC). Animals were euthanized at 6, 12, 24, 48 and 72 h post PH (n=9-12/group/time) to evaluate liver regeneration rate, mitotic index, liver content, serum and tissue levels of Interleukin 6 (IL-6) and serotonin and its receptor 5-hydroxytryptamine type 2B (5Ht2b). Survival rate in 10 days was evaluated in a different set of animals (n=20/group).

Results: Platelets group showed the highest survival rate despite the lowest liver regeneration rate at any time point. Mitotic and BrdU index showed no difference between groups. However, the number of hepatocytes was higher and the internuclear distance was shorter for PLT group. Liver dry weight was similar in both groups indicating that water was the main responsible factor for the weight difference. Gene expression of IL-6 in the liver was significantly higher in EC group 6 h after PH, whereas 5Ht2b was up-regulated at 72 h in PLT group.

Conclusions: Platelets enhance survival of animals with 90% PH, probably by an early protective effect on hepatocytes and the increase in growth factor receptors.

Keywords: acute liver failure; animal model of acute liver failure; capsules; hepatectomy; platelets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / physiology*
  • Disease Models, Animal*
  • Drug Compounding
  • Enzyme-Linked Immunosorbent Assay
  • Hepatectomy / methods*
  • Immunohistochemistry
  • Interleukin-6 / metabolism
  • Kaplan-Meier Estimate
  • Liver / metabolism
  • Liver Failure, Acute / etiology
  • Liver Failure, Acute / pathology*
  • Liver Regeneration / physiology*
  • Male
  • Oxazines
  • Platelet Transfusion / methods*
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric

Substances

  • Interleukin-6
  • Oxazines
  • nile red