Cardioprotective Effects of Fisetin Against Sodium Arsenite-Induced Toxicity in Experimental Rats: Roles of the Nrf2/HO-1 and Bax/Bcl-2/Caspase-3 Pathways
Year: 2025
Type: article
Abstract: Background and Objective: Sodium arsenite, a pesticide, is well known to induce cardiotoxicity via myocardial apoptosis. Fisetin, a plant, has antioxidant, anti-inflammatory and anti-apoptotic potential. This study aimed to evaluate the putative mechanism of action of fisetin against sodium arsenite-induced cardiotoxicity in experimental rats. Materials and Methods: Cardiotoxicity was induced in male Sprague-Dawley rats (200–230 g, n = 15, in each group) using sodium arsenite (5 mL/kg, p.o., 28 days) and concomitantly treated with either coenzyme Q10 (10 mg/kg) or fisetin (5, 10 and 25 mg/kg, p.o.) orally for 28 days. Various biochemical, molecular, and histopathological analyses were performed to evaluate the efficacy of fisetin against cardiotoxicity. Data were analyzed by one-way Analysis of Variance (ANOVA), while Tukey’s multiple range tests were applied for post hoc analysis. Results: Chroni carsenite administration promoted a significant (p < 0.001) increase in relative heart weight and alterations in electrocardiographic, hemodynamic, and left ventricular function parameters, which were effectively and dose-dependently attenuated (p < 0.01 and p < 0.001) by fisetin (10 and 25 mg/kg). Moreover, fisetin treatment also markedly decreased elevated serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and lipid levels. Arsenite-induced elevated cardiac oxido-nitrosative stress was also efficiently and dose-dependently decreased (p < 0.01 and p < 0.001) by fisetin. Following arsenite exposure, the mRNA expressions of cardiac nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and B-cell lymphoma 2 (Bcl-2) were downregulated, and Bax and Caspase-3 mRNA were up-regulated; these expressions were likewise effectively and dose-dependently (p < 0.01 and p < 0.001) inhibited by fisetin. Histopathological observations of the heart suggested that fisetin attenuated arsenite-induced myocardial aberrations. Conclusion: Fisetin effectively mitigates sodium arsenite-induced cardiotoxicity in experimental rats. The protective effects of fisetin are associated with antioxidant (Nrf2/HO-1) and apoptotic (Bax/Bcl-2 and caspase-3) pathways in experimental rats. Thus, fisetin can be considered a potential phytoconstituent in managing pesticide-induced cardiotoxicity.
DOI: 10.31083/ijp44191
Authors: Ting Zhao, Li Xu
Institution: Qingdao Municipal Hospital
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4414064732