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

ABSTRACT

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.