The effectiveness of citicoline administration on hepatic regeneration in an experimental hepatectomy model

Objective: This study aimed to assess the effects of citicoline on liver regeneration following experimental partial hepatectomy in rats using biochemical, histopathological, and immunohistochemical methods. The hypothesis was that citicoline would exhibit hepatoprotective and regenerative benefits in this model. Materials and Methods: Wistar rats underwent 30% partial hepatectomy and were randomized into citicoline-treated and control groups. The treatment group received intraperitoneal citicoline postoperatively. Biochemical assessments included aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and direct bilirubin, albumin, prothrombin time (PT), and international normalized ratio (INR). Relative liver weight (RLW) was calculated. Histopathological evaluation comprised necrosis, polymorphonuclear leukocyte (PMNL) infiltration, cytoplasmic vacuolization, bile duct proliferation, binucleation, central vein expansion, mitotic count, and a composite histopathological score. Proliferation was assessed immunohistochemically with Ki-67 staining. Statistical analysis used appropriate parametric or non-parametric tests, with chi-square for categorical variables (p<0.05). Results: Mean total and direct bilirubin levels were 0.05 mg/dL, albumin was 3.28 g/dL, and coagulation parameters remained within physiological ranges across groups. While percentage weight loss was lower in the treatment group (5.51±6.92%) than controls (10.89±11.30%), this was not statistically significant (p=0.745). Citicoline significantly reduced necrosis (30.0% vs. 72.2%; p=0.023) and PMNL infiltration (40.0% vs. 72.2%; p=0.046). The treatment group showed greater cytoplasmic vacuolization (50.0% vs. 16.7%; p=0.031) and bile duct proliferation (dense: 45.0% vs. 11.1%; p=0.049). RLW favored citicoline (p=0.043). There were no significant differences in the composite histopathological score or Ki-67. Conclusion: In this model, citicoline administration was associated with lower transaminase levels, reduced necrosis and inflammation, and increased bile duct proliferation, cytoplasmic vacuolization, and RLW, suggesting anti-inflammatory, hepatoprotective, and regeneration-supporting effects. The lack of group differences in Ki-67 and the overall score may reflect dependencies on timing, dosage, or marker sensitivity. Larger, multi-time-point studies are warranted to clarify citicoline's regenerative potential. Keywords: Partial hepatectomy, Citicoline, Liver, Regeneration