Intraoperative Options to Stimulate the Reparative Liver Regeneration in the Experiment

Background. Primary and secondary malignant neoplasms and liver damage affect more than 500 million people worldwide; one million of these people die annually. Secondary malignant neoplasms of the liver occur in every fourth cancer patient, 60% of them require liver resection. As reported, post-resection liver failure occurs in 32–60% of cases. Thus, at the current stage of medicine development, the search for novel options to stimulate reparative liver regeneration remains a challenging issue in surgery. 
The aim of the study was to stimulate post-resection liver regeneration by intraoperative intrahepatic and intraperitoneal administration of cyanocobalamin and ademetionine in an experiment.
Materials and methods. This research is a prospective randomized study carried out at the Research Institute of Experimental Biology and Medicine, N.N. Burdenko Voronezh State Medical University (VSMU), Ministry of Health of the Russian Federation. Experiments involved 192 mature male Wistar rats, who underwent conventional liver resection (CLR) equal approximately to 70% of the initial liver volume, according to the approach proposed by G. Higgins and R. Anderson. The effect of intraperitoneal administration of ademetionine and cyanocobalamin on post-resection liver regeneration was investigated in the first block of the study. The effect of intraoperative intrahepatic injections and intrahepatic administration of drugs on post-resection liver regeneration was tested in the second block of the study. The combined use of ademetionine and cyanocobalamin and their effect on post-resection liver regeneration was studied in the third block of the study. Physical examination and laboratory findings were used to assess reparative processes. The data were processed statistically using the STATGRAPHICS Centurion 18 software package, version 18.1.12 (Statgraphics Technologies, Inc., USA). The analysis of variance (ANOVA) was applied to compare mean values for eight different group.
Results. The study detected that intraperitoneal administration of ademetionine helps to normalize the general condition and biochemical parameters in 77.78% of animals. Intraperitoneal administration of cyanocobalamin does not have a significant effect on biochemical parameters, including oxidative stress. Intrahepatic administration of cyanocobalamin helps to increase the reparative liver potential, results in decreased rates of cytolysis and cholestasis syndromes, restoration of carbohydrate and fat metabolism, and increased expression of growth factors. Intrahepatic administration of ademetionine leads to decreased regenerative liver potentials, disruption of its functional activity, and decreasd protective antioxidant properties. 
Conclusion. Thus, the optimal intraoperative option to stimulate reparative liver regeneration in the experiment is the intrahepatic administration of cyanocobalamin supplemented by intraperitoneal administration of ademetionine. In 7 days after liver resection, this helps normalize biochemical parameters, relieves oxidative stress, and increases IL-1β and TGF-β1. In 14 days after resection, the abovementioned events  lead to restoration of 95.04% of the initial liver weight, if compared with intraperitoneal administration of cyanocobalamin and ademetionine (p<0,05).