Liposomal Nano-Curcumin Attenuates Cisplatin-Induced Hepatotoxicity in Rats with Concomitant Regulation of Wnt/β-Catenin/GSK-3β and Nrf2 Signaling

Abstract

Objective: This research examined the effectiveness of liposomal N-Curcumin (N-Cur) against Cis-diamminedichloroplatinum (CDDP)-induced hepatotoxicity, specifically examining its ability to influence the Wnt/β-catenin/GSK-3 pathway and associated molecular markers. Methods: Male Wistar rats were treated for 14 days with oral N-Cur (80 mg/kg) and with a single intraperitoneal dose of CDDP (7 mg/kg) administered on day 7. Hepatic integrity was assessed through liver injury markers, histopathological examination, and biochemical analysis of oxidative stress (SOD, GSH, and MDA), inflammation (IL-10, TNF-α, CRP, and NF-κB p65), and signaling protein expression (β-catenin, Nrf2, and GSK-3). Results: CDDP administration resulted in significant hepatic damage, characterized by elevated injury markers and distorted tissue architecture. It induced severe oxidative stress (increased MDA; decreased GSH and SOD) and a robust inflammatory response. At the molecular level, CDDP suppressed the cytoprotective β-catenin and Nrf2 pathways while increasing GSK-3. Conversely, N-Cur treatment effectively reversed these pathological shifts by restoring antioxidant defenses, inhibiting pro-inflammatory mediators, and normalizing the Wnt/β-catenin/GSK-3 signaling axis. Conclusions: Liposomal N-Cur demonstrates significant potential as a hepatoprotective agent when administered concomitantly with CDDP chemotherapy. N-Cur mitigates oxidative damage and inflammation, thereby preserving hepatic function during CDDP-based chemotherapy. In addition, these favorable effects were associated with modulation of the Wnt/β-catenin/GSK-3 and Nrf2 pathways.