Fraxinus excelsior L. for Prevention of Capecitabine-induced Enterocolitis in Rat: An Integrated Biochemical, Molecular, and Histopathological Study

Abstract

Background: Chemotherapy drugs damage intestinal cells, weakening the intestinal barrier. This damage results in higher permeability, which enables bacteria and toxins to enter the intestinal tissue. Purpose: This study aimed to explore the protective effects of Fraxinus excelsior L. (F. excelsior) extract against Capecitabine (CT)-induced enterocolitis. Methods: Fifty Wistar rats were divided into five groups: sham, F. excelsior (750 mg/kg orally), CT (500 mg/kg orally), and two co-treatment groups receiving CT with F. excelsior (500 and 750 mg/kg orally). After 50 days, rats were sacrificed, and blood samples were collected for various analyses. Biochemical assessments included measurements of serum nitric oxide, catalase, glutathione peroxidase, and superoxide mutase enzymes. Tissue oxidative stress was evaluated through FRAP, thiol, and TBARS levels. Pro-inflammatory cytokines were quantified using ELISA, and apoptosis was assessed through the evalution of p53/Bax/Bcl-2 pathway. Histopathological examination affirmed the preservation of tissue structure in groups treated with F. excelsior extract. Results: F. excelsior extract reduced intestinal cell apoptosis and elevated the expression of intestinal aquaporin (AQP) genes/proteins by enhancing antioxidant enzymes and diminishing free radicals. Additionally, the extract modulated inflammatory cytokine levels, regulated antidiuretic hormone (ADH) and arginine vasopressin (AVP) levels, maintaining serum and intestinal osmotic balance. The study also revealed decreased expression of pro-inflammatory cytokines and a positive impact on water homeostasis-related genes (AQP3, AQP8, AQP10). Conclusion: The study concludes that F. excelsior extract exhibits potential benefits in treating enterocolitis in individuals undergoing chemotherapy, emphasizing its ability to mitigate oxidative stress, inflammation, apoptosis, and maintain osmotic balance.