Pyrvinium Attenuates Amiodarone-Induced Pulmonary Fibrosis in Male Rats: Association with Modulation of Wnt/β-Catenin Related Proteins

Background/Objectives: Amiodarone (AmoD) is an effective antiarrhythmic drug whose use is limited by life-threatening pulmonary fibrosis. Although Wnt/β-catenin signaling contributes to several lung diseases, its involvement in AmoD-induced pulmonary fibrosis remains unknown. This study investigated whether Wnt/β-catenin signaling is altered during AmoD-induced pulmonary fibrosis and whether its pharmacological modulation with pyrvinium (Pyrv) attenuates this toxicity.

Methods

Rats were allocated into four groups and treated for five weeks as follows: normal control, AmoD (30 mg/kg/day), Pyrv (60 µg/kg/day), and AmoD + Pyrv. Pulmonary injury and fibrosis were evaluated using histopathological examination, Masson’s trichrome staining, immunohistochemical assessment of collagen I, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1), and measurement of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and Th1/Th2-related cytokines. Wnt/β-catenin-associated proteins, including Wnt3a, active β-catenin, and glycogen synthase kinase-3β (GSK-3β), were evaluated by Western blotting.