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