Hepatocellular necrosis, apoptosis, and proliferation after transcatheter arterial embolization or chemoembolization in a standardized rabbit model

J Vasc Interv Radiol. 2011 Nov;22(11):1606-12. doi: 10.1016/j.jvir.2011.08.005. Epub 2011 Sep 29.

Abstract

Purpose: To evaluate the effect of transcatheter arterial chemoembolization versus transcatheter arterial embolization on hepatocellular damage, apoptosis, proliferation, and proinflammatory response in a rabbit VX2 tumor model.

Materials and methods: Rabbits implanted with VX2 tumors in left liver lobes were randomly divided into three groups: a control group (n = 9) that underwent infusion of distilled water into the left hepatic artery, an embolization group (n = 15) that underwent left hepatic artery embolization with polyvinyl alcohol (PVA) particles, and a chemoembolization group (n = 15) that underwent left hepatic artery infusion of a mixture of 10-hydroxycamptothecin and iodized oil followed by PVA embolization. Serum and liver samples were collected at 6 hours, 3 days, and 7 days postoperatively. Liver damage was measured by liver function tests and histologic analysis. Ki-67 immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling were performed to quantify proliferating and apoptotic cells. Serum tumor necrosis factor (TNF)-α levels were measured to assess proinflammatory response.

Results: Compared with embolization, chemoembolization caused liver injury with a greater increase in serum alanine aminotransferase and aspartate aminotransferase levels on days 3 and 7; histologic analysis showed increased hepatic necrosis in adjacent liver tissue beginning at day 3 and increased serum levels of TNF-α at 6 hours. By contrast, chemoembolization resulted in a slower increase in hepatocyte proliferation. Additionally, increased apoptotic hepatocytes were observed after embolization and chemoembolization.

Conclusions: In contrast to embolization, nonsuperselective transcatheter arterial chemoembolization increased hepatocellular damage and stimulated systemic proinflammatory cytokine release, but inhibited hepatocyte proliferation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine Transaminase / blood
  • Angiography, Digital Subtraction
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Apoptosis / drug effects*
  • Aspartate Aminotransferases / blood
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Proliferation / drug effects*
  • Chemoembolization, Therapeutic* / adverse effects
  • Embolization, Therapeutic* / adverse effects
  • Hepatic Artery*
  • In Situ Nick-End Labeling
  • Iodized Oil / administration & dosage
  • Ki-67 Antigen / metabolism
  • Liver Function Tests
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / pathology
  • Liver Neoplasms, Experimental / therapy*
  • Liver Regeneration / drug effects
  • Magnetic Resonance Imaging
  • Necrosis
  • Polyvinyl Alcohol / administration & dosage
  • Rabbits
  • Time Factors
  • Tomography, X-Ray Computed
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Antineoplastic Agents, Phytogenic
  • Ki-67 Antigen
  • Tumor Necrosis Factor-alpha
  • Iodized Oil
  • Polyvinyl Alcohol
  • 10-hydroxycamptothecin
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Camptothecin