Hepatotrophic effect of folinic acid in rats

Hepatic ischemia hinders the proliferative response of hepatocytes, necessary to restore the liver/body ratio after liver resection/transplantation. Folinic acid administered during the ischemic period following 70% hepatectomy plus 15 min of normothermic liver ischemia has restored the regenerative response to the levels of normoperfused livers. This unexpected finding has guided us to design the present study in order to find out whether the folinic acid is an hepatotrophic substance or not. Sprague-Dawley rats submitted to partial (40 or 70%) hepatectomies were used. Saline (2 cc) or folinic acid (2.5 mg/kg) have been administered i.v. Forty-eight hours after hepatectomy the hepatocyte's DNA content has been assessed by means of a cytophotometric technique, and the percentage of regenerating hepatocytes (PRH) has been calculated. Folinic acid administration has significantly increased the PRH in both resting (5.1 vs 1.2) and regenerating livers (70% hepatectomy) (22.2 vs 41) when compared with nontreated groups. Folinic acid administration after liver ischemia plus hepatectomy has shown similar results, corroborating our previous study. Although its mechanisms of augmentation of liver regeneration remain unclear and further studies are required, folinic acid seems to be a promising therapeutic tool in liver surgery.