Hepatic regeneration in a rat model is impaired by chemotherapy agents used in metastatic colorectal cancer

European Journal of Surgical Oncology : the Journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
C HubertI Leclercq

Abstract

Administering Oxaliplatin prior to resection of colorectal liver metastases often induces a Sinusoidal Obstruction Syndrome (SOS), which can affect postoperative patient outcome. Bevacizumab (Anti-VEGF-A) can decrease the severity of SOS and the associated risk of postoperative liver failure. We investigated the impact of both Oxaliplatin (Oxali) and Bevacizumab on liver regeneration in a rat model. Male Wistar rats underwent a 70% partial hepatectomy (PH) 3 days after a 2 ml intraperitoneal injection of either saline (controls, n = 17), or Oxaliplatin 10, 20 or 50 mg/kg, 5-Fluorouracil 100 mg/kg (5-FU) and Bevacizumab 5 or 10 mg/kg in various combinations (total 98 rats, 11 groups, n = 5-18/group). Liver regeneration was assessed by remnant liver weight recovery and cell proliferation by immunodetection of BrDU incorporation (days 1, 2, 3, 7). Hepatic mRNA expression levels of VEGF-A and of its 2 receptors (Flt-1 and KDR) were quantified by PCR technique. Liver regeneration was impaired for 3 days post PH by Oxali 20 alone and Oxali 10 + 5-FU, without any rescue effect by neither Bevacizumab 5 nor 10 mg/kg. Unlike in humans, there were no sinusoidal changes. VEGF-A mRNA expression and receptor 2 (KDR) expressions decreased 24 ...Continue Reading

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Citations

May 26, 2017·The British Journal of Surgery·J ZhaoUNKNOWN Chemotherapy-Associated Liver Injury (CALI) consortium
Oct 13, 2019·Cancer Chemotherapy and Pharmacology·Kazuhiro TadaMasafumi Inomata
Jun 18, 2020·Therapeutic Advances in Gastroenterology·Alexandra Gangi, Shelly C Lu
Nov 2, 2018·International Journal of Molecular Sciences·Ana Isabel Álvarez-MercadoCarmen Peralta

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