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

SIMPLE SUMMARY: 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 µm(2), and 49.91 ± 15.38 µm(2); 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.