Liver regeneration after extensive hepatectomy in rats: effect of preoperative chemotherapy with intravenous 5-fluorouracil.

IF 1.1 4区医学 Q3 SURGERY

Acta cirurgica brasileira Pub Date : 2022-01-01 DOI:10.1590/acb370901

Marciano Anghinoni, Edimar Leandro Toderke, Thaísa Sami Nakadomari, Tiago Kuchnir Martins de Oliveira, Felipe Pedrotti Locatelli, Jorge Eduardo Fouto Matias

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Abstract

Purpose: To evaluate the effect of preoperative intravenous chemotherapy with 5-fluorouracil on liver regeneration in an experimental model of major hepatectomy in rats.

Methods: Wistar rats were divided into two groups of 20 animals each and submitted to 70% hepatectomy 24 h after intravenous injection of 5-fluorouracil 20 mg/kg (fluorouracil group, FG) or 0.9% saline (control group, CG). After hepatectomy, each group was subdivided into two subgroups of 10 animals each according to the day of sacrifice (24 h or 7 days). Liver weight during regeneration, liver regeneration rate using Kwon formula, and the immunohistochemical markers proliferating cell nuclear antigen (PCNA) and Ki-67 were used to assess liver regeneration.

Results: At early phase (24 h after hepatectomy) it was demonstrated the negative effect of 5-fluorouracil on liver regeneration when assessed by Kwon formula (p < 0.0001), PCNA analysis (p = 0.02). With regeneration process complete (7 days), it was possible to demonstrate the sustained impairment of chemotherapy with 5-fluorouracil on hepatocytes regeneration phenomenon when measured by Kwon formula (p = 0.009), PCNA analysis (p = 0.0001) and Ki-67 analysis (0.001).

Conclusions: Preoperative chemotherapy with intravenous 5-fluorouracil negatively affected the mechanisms of liver regeneration after major hepatectomy in rats.

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大鼠广泛肝切除术后肝再生:术前静脉注射5-氟尿嘧啶化疗的影响。

目的:探讨术前5-氟尿嘧啶静脉化疗对大鼠肝切除术后肝脏再生的影响。方法:Wistar大鼠分为两组，每组20只，在静脉注射5-氟尿嘧啶20 mg/kg(氟尿嘧啶组，FG)或0.9%生理盐水(对照组，CG) 24 h后行70%肝切除术。肝切除术后，每组按献祭日期(24 h或7 d)再分为2个亚组，每组10只。肝再生过程中肝脏重量、Kwon配方肝再生率、增殖细胞核抗原(PCNA)和Ki-67免疫组化标志物评价肝再生。结果:在早期(肝切除术后24 h)，采用Kwon公式评估5-氟尿嘧啶对肝再生的影响(p < 0.0001)， PCNA分析(p = 0.02)。再生过程完成(7天)后，通过Kwon公式(p = 0.009)、PCNA分析(p = 0.0001)和Ki-67分析(0.001)，可以证明5-氟尿嘧啶化疗对肝细胞再生现象的持续损害。结论:术前静脉注射5-氟尿嘧啶化疗对大鼠肝切除术后肝脏再生机制有负面影响。

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