Hepatic Inflammation and Apoptosis in Socially Isolated Rats: Effects of Vortioxetine Treatment

Background: Depression and chronic psychosocial stress can induce systemic inflammation and oxidative stress that may extend beyond the central nervous system to peripheral organs such as the liver. Social isolation is a widely used rodent model in depression research; however, its hepatic consequences and the potential protective effects of antidepressant treatment remain incompletely characterized. Objectives: This study aimed to investigate whether social isolation induces hepatic inflammation and apoptosis in rats and to evaluate the effects of vortioxetine treatment on these hepatic alterations. Methods: Forty male Wistar albino rats were randomly allocated into four groups (n = 10/group): Control (C), Social Isolation (SI), Vortioxetine (V), and Social Isolation + Vortioxetine (SI+V). Social isolation was maintained for four weeks. Vortioxetine (10 mg/kg/day, intraperitoneally) or vehicle (dimethyl sulfoxide, 1 mL/kg) was administered from days 17 to 31. Liver tissues were examined histopathologically using hematoxylin-eosin and Masson's trichrome staining. Apoptosis was assessed using a terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and caspase-3 immunoreactivity. Immunohistochemical analyses were performed for tumor necrosis factor-alpha, nuclear factor-kappa B p65, and cytokeratin-18. Hepatic interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Results: The SI group exhibited marked sinusoidal dilatation, erythrocyte extravasation, hepatocellular ballooning, and inflammatory infiltration, accompanied by increased tumor necrosis factor-alpha, nuclear factor-kappa B p65, and caspase-3 immunoreactivity; increased terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity; and elevated hepatic interleukin-6 levels (P < 0.001). Vortioxetine treatment in isolated rats attenuated these inflammatory and apoptotic responses, resulting in lower histopathological damage scores and better cytokeratin-18 preservation than in the SI group. Masson's trichrome staining showed no significant collagen accumulation among groups (P > 0.05). Conclusions: Social isolation was associated with increased hepatic inflammation and apoptosis, as demonstrated by histopathological, immunohistochemical, and biochemical findings. Vortioxetine treatment was associated with partial attenuation of these alterations. These findings are limited to the measured endpoints and do not establish direct functional effects.