Nanocurcumin Attenuates Doxorubicin‐Induced Cardiotoxicity by Activating the Wnt/β‐Catenin/GSK‐3β Signaling Axis in Wistar Rats

Doxorubicin (DOX)-induced cardiotoxicity remains a major therapeutic limitation, emerging at the intersection of oxidative stress, mitochondrial impairment, and disruption of survival signaling pathways. The Wnt/β‑catenin-GSK‑3β pathway is an essential regulator of cardiomyocyte survival. To assess the cardioprotective potential of nanocurcumin (N-Cur) in this condition, twenty-four Wistar rats were divided into four groups (N-Cur; 80 mg/kg, oral) was given for 2 weeks, while DOX was administered on day seven as a single dose. N-Cur treatment significantly standardized DOX‑induced elevations in cTnI and CK‑MB, restored cardiac antioxidants (GSH, SOD), decreased MDA levels with p ≤ 0.01, significantly restored Nrf2, and reduced pro‑inflammatory mediators (TNF‑α, IL‑6, NF‑κB‑p65) (p < 0.001), thereby augmenting its twin roles as a potent anti-inflammatory and antioxidant agent. The histopathological changes and inflammatory infiltration caused by DOX were significantly diminished following N-Cur treatment. Further, DOX inhibited Wnt/β‑catenin signaling and increased GSK‑3β expression, whereas N-Cur reversed these changes in immunohistochemistry studies. Collectively, these findings indicate that N-Cur provides significant cardiomyocyte protection and efficiently modifies the Wnt/β‑catenin-GSK‑3β axis.