Nanocurcumin mitigates Fluoxetine-induced hepatotoxicity: histological, immunohistochemical and molecular in vivo study

Fluoxetine (FUX) is a selective serotonin reuptake inhibitor commonly used as a first-line treatment for depression. However, there are concerns about its potential hepatotoxicity. On the other hand, nanocurcumin (N-CUR) has anti-inflammatory, antioxidant, anticancer, and antimicrobial properties, showing promise in various disorders treatment. This study aims to investigate the potential protective role of N-CUR against FUX-induced hepatotoxicity. Four groups of healthy adult male Wistar albino rats, each consisting of 12 rats, were used. The control group received a vehicle, while the other groups were administered N- CUR (100 mg/kg/day), FUX (10 mg/kg/day), or a combination of both treatments via gavage for 8 weeks. Liver biopsies from all rats were subjected to histological, immunohistochemical, mRNA gene expression, and oxidative stress assessments. FUX Exposure induced hepatic vascular abnormalities, inflammation, bile duct proliferation, cholangitis, steatosis, fibrosis, glycogen depletion, Kupffer cells hyperplasia, mast cells, and stellate cell proliferation. In addition, FUX downregulated mRNA gene expressions of PPAR-γ but boosted Nrf2 and heme oxygenase-1 (HO-1). Furthermore, FUX increased iNOS protein expression and dysregulated oxidative/antioxidant balance. On the other hand, N-CUR supplementation mitigated partially or completely the FUX-induced histological alterations, upregulated Nrf2, HO-1, PPAR-γ immunohistochemical and mRNA gene expressions, ameliorated oxidative stress, decreased inflammation and apoptosis. The present study’s findings confirm the protective role of N-CUR against FUX-induced hepatotoxicity and indicate its antioxidant, anti-inflammatory, and antifibrotic properties. However, further research is needed to elucidate the underlying mechanisms and the molecular pathway involved in the protective role of N-CUR in FUX- induced hepatotoxicity.