Bevacizumab Allows Preservation of Liver Function and its Regenerative Capacity after Major Hepatectomy

Author(s):

Amparo Valverde, Rubén Ciria, Javier Caballero-Villarraso*, Patricia Aguilar-Melero, Gustavo Ferrín, Isidora Ranchal, Clara Linares, Carmen Herencia, Sandra González-Rubio, Manuel de la Mata, Álvaro Naranjo and Javier Briceño   Pages 1388 - 1398 ( 11 )

Abstract:

Background: Parallel to the safety of liver resections, new chemotherapy drugs have emerged for the control of liver metastases. However, there is unclear evidence about the combination of intensive BVZ-therapy and extended resections. The main aim was to analyse the impact of Bevacizumab (BVZ) in terms of liver safety and tolerability in two experimental models: a basal-toxicity situation and after major hepatectomy. <p></p> Methods: Eighty male-Wistar rats were grouped as toxicity analysis (sham-operated rats-OS-) and regeneration after- surgery analysis (hepatectomy rats-H-). Eight further subgroups were created according to sacrifice (6- hours-6h- or 24-hours-24h-) and dose (μg) of BVZ (none, 100, 200, 400). Several measurements were performed, including biochemical serum samples, histopathological analysis, cytokines (IL-6, TNF-α, TGF-β), oxidative-stress (GSH/GSSG, ATP), lipid-peroxidation (TBARS) and epidermal and vascular endothelium growth-factors (EGF and VEGF). <p></p> Results: In the toxicity analysis, safe results with BVZ were observed, with no significant differences among the groups. A trend towards a lower oxidative status was observed in the OS 6 h-100, -200 and -400 versus the OS 6 h-none group. Similar results were observed in the hepatectomy model, with stable oxidative-stress-index and IL-6, TNF- α, and TGF- β levels. Despite higher lipid peroxidation status, overall regeneration was preserved. As expected, VEGF was almost undetectable in BVZ-treated groups after resection, but not in the non-resection group. <p></p> Conclusion: It was concluded that liver status was not impaired by BVZ even at the high-dose. Similarly, liver regeneration after extended hepatectomy in BVZ-treated animals was well-preserved. Extended liver resections may be encouraged in BVZ-treated patients due to its excellent tolerability and good liver regeneration status.

Keywords:

Neoadjuvant chemotherapy, angiogenesis inhibitor, monoclonal antibody, regeneration, liver toxicity, hepatotoxicity, hepatectomy.

Affiliation:

Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Clinical Analyses Service & Department of Biochemistry and Molecular Biology, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Liver Research Unit, IMIBIC/Reina Sofia Hospital/University of Cordoba, Cordoba, Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba, Unit of Hepatobiliary Surgery and Liver Transplantation, IMIBIC/Reina Sofia Hospital/University of Cordoba, Córdoba

Graphical Abstract:

Read Full-Text article