Esculetin Loaded Chitosan Nanoparticles (ESC-CNPs) Ameliorates 7, 12 Dimethylbenz [a] Anthracene (DMBA) Induced Breast Cancer in Rat Model

Aim: This study aimed to explore the chemopreventive potential of Esculetin-loaded Chitosan Nanoparticles (ESC-CNPs) against mammary carcinogenesis induced by 7,12-Dimethylbenz[a]Anthracene (DMBA) in female Sprague-Dawley rats. Materials and Methods: DMBA, administered subcutaneously at a dose of 25 mg/rat near the mammary gland, triggered the formation of breast tumors. Female Sprague-Dawley rats were induced with mammary tumors via a single subcutaneous injection of DMBA. The treatment groups received ESC-CNPs orally at dosages of 25, 50 and 100 mg/kg body weight (bw). Biochemical parameters, including lipid peroxidation (TBARS and LOOH), antioxidant status (SOD, CAT, GPX and GSH), phase I (CYP450, Cyt-b5) and phase II (GST, GR) enzymes and lipid profiles (TC, TG, PL, FFA), were evaluated in plasma and breast tissues. Additionally, the expression of VEGF, NF-kB and Cyclin D1 was analyzed through histopathology and western blotting. Results: DMBA-induced rats exhibited decreased body weight, increased tumor volume and incidence, elevated lipid peroxidation, reduced antioxidant status, altered liver and mammary tissue enzyme levels and disrupted lipid profiles. ESC-CNPs treatment, particularly at 100 mg/kg bw, significantly reduced tumor occurrence, normalized biochemical markers and downregulated VEGF, NF-kB and Cyclin D1 expression in mammary tissues. Conclusion: ESC-CNPs, at a dose of 100 mg/kg bw, demonstrated a potent chemopreventive effect against DMBA-induced mammary cancer, as evidenced by biochemical, histopathological and molecular findings.