Protective Effects of Esculetin at two Different Doses on Oxidative Stress, Inflammation, and Fibrotic Changes in AlCl₃-Induced Cardiotoxicity in Rats

Objective: Aluminum chloride (AlCl₃) is an environmental toxicant that promotes cardiotoxicity primarily by inducing oxidative stress and inflammatory responses. Esculetin (ESC), which is a naturally occurring coumarin derivative, possesses antioxidant, anti-inflammatory, and antifibrotic activities. This study evaluated the protective effects of ESC against AlCl₃-induced cardiotoxicity, with a focus on dose-related responses.Methods: 35 male Wistar albino rats were randomly assigned to five experimental groups (n=7 per group): Control, Vehicle, AlCl₃ (10 mg/kg), AlCl₃ + ESC50 (50 mg/kg), and AlCl₃ + ESC100 (100 mg/kg). All experimental treatments were administered orally once daily throughout the 14-day study period. Cardiac tissue levels of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were determined to assess oxidative stress. Tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) were measured to evaluate the inflammatory response. Histopathological changes and the immunoreactivity of inducible nitric oxide synthase (iNOS) and alpha-smooth muscle actin (α-SMA) were also evaluated.Results: AlCl₃ exposure led to increased MDA levels and decreased GSH levels, with reduced SOD and CAT activities in heart tissue (P