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.
Methods: Eighty male-Wistar rats were grouped as toxicity analysis (sham-operated rats-OS-) and regenerationafter-
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).
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
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.