Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Gutiérrez Sáenz de Santa María, Jorge; Herrero de la Parte, Borja; Gutiérrez-Sánchez, Gaizka; Ruiz Montesinos, Inmaculada; Iturrizaga Correcher, Sira; Mar Medina, Carmen; García-Alonso, Ignacio

doi:10.3390/cancers14020371

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Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Jorge Gutiérrez Sáenz de Santa María

¹,

Borja Herrero de la Parte

^2,3,*

Gaizka Gutiérrez-Sánchez

⁴,

Inmaculada Ruiz Montesinos

^2,5,*,

Sira Iturrizaga Correcher

⁶

Carmen Mar Medina

⁶

and

Ignacio García-Alonso

^2,3

Department of Orthopedic Surgery, Central University Hospital of Asturias (HUCA), ES33011 Oviedo, Spain

Department of Surgery and Radiology and Physical Medicine, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, ES48940 Leioa, Spain

Interventional Radiology Research Group, Biocruces Bizkaia Health Research Institute, ES48903 Barakaldo, Spain

⁴

Department of Anesthesiology, Santa Creu i Sant Pau University Hospital, ES08025 Barcelona, Spain

⁵

Department of Gastrointestinal Surgery, Donostia University Hospital, ES20014 Donostia, Spain

⁶

Department of Clinical Analyses, Galdakao-Usansolo Hospital, ES48960 Galdakao, Spain

Authors to whom correspondence should be addressed.

Academic Editors: Ryota Masuzaki and Tatsuo Kanda

Cancers 2022, 14(2), 371; https://doi.org/10.3390/cancers14020371

Received: 30 November 2021 / Revised: 30 December 2021 / Accepted: 7 January 2022 / Published: 12 January 2022

(This article belongs to the Special Issue Liver Cancer: Improving Standard Diagnosis and Therapy)

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Fewer than 30% of patients with liver metastases are eligible for major liver resection, because liver remaining after such a surgery would be insufficient to cover the patient’s needs; this is called a low percentage of future liver remnant (FLR). Folinic acid (FA) has been shown to play a crucial role in cellular synthesis, regeneration, and nucleotide and amino acid biosynthesis. The aim of this piece of research was to evaluate the effect of FA as a potential hypertrophic hepatic enhancer agent after selective portal vein ligation (PVL) to ensure adequate FLR. We have confirmed in our rodent model that FA accelerates liver regeneration after PVL and enhances recovery of liver function. These findings may allow more patients to be eligible for liver resection without jeopardizing postoperative liver function.

Abstract

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm², and 49.91 ± 15.38 µm²; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL. View Full-Text

Keywords: selective portal vein ligation; folinic acid; hepatotrophic; rodent model; future liver remnant

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MDPI and ACS Style

Gutiérrez Sáenz de Santa María, J.; Herrero de la Parte, B.; Gutiérrez-Sánchez, G.; Ruiz Montesinos, I.; Iturrizaga Correcher, S.; Mar Medina, C.; García-Alonso, I. Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats. Cancers 2022, 14, 371. https://doi.org/10.3390/cancers14020371

AMA Style

Gutiérrez Sáenz de Santa María J, Herrero de la Parte B, Gutiérrez-Sánchez G, Ruiz Montesinos I, Iturrizaga Correcher S, Mar Medina C, García-Alonso I. Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats. Cancers. 2022; 14(2):371. https://doi.org/10.3390/cancers14020371

Chicago/Turabian Style

Gutiérrez Sáenz de Santa María, Jorge, Borja Herrero de la Parte, Gaizka Gutiérrez-Sánchez, Inmaculada Ruiz Montesinos, Sira Iturrizaga Correcher, Carmen Mar Medina, and Ignacio García-Alonso. 2022. "Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats" Cancers 14, no. 2: 371. https://doi.org/10.3390/cancers14020371

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Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

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