Comparative histological and biochemical evaluation of phenytoin and nifedipine in enhancing wound healing in rat model

Abstract

Purpose: To investigate the regenerative effects of phenytoin and nifedipine in a full-thickness cutaneous wound model in male rats.Methods: Rats were randomly and equally divided into 4 groups. Group A was negative control (unwounded skin), group B was positive control (untreated wound), group C received phenytoin (1 % topical application, once daily), and group D received nifedipine (1 % topical application, once daily) for 12 consecutive days. Tissue levels of interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) were assessed after 6 and 12 days of treatment. Histopathological examination was performed to evaluate tissue regeneration and wound healing progression.Results: Phenytoin significantly increased IL-10 and reduced TNF-α compared to control groups (p < 0.05). Phenytoin also significantly increased VEGF (p < 0.05) and bFGF (p < 0.05) compared with the control, reflecting enhanced angiogenic and fibroblast activity. Furthermore, nifedipine significantly increased IL-10 and decreased TNF-α compared to positive control (p < 0.05). Phenytoin-treated wounds demonstrated advanced re-epithelialization, organized granulation tissue, and increased extracellular matrix deposition. Treatment with nifedipine showed moderate improvement characterized by reduced inflammation and progressing remodeling.Conclusions: Phenytoin significantly increased VEGF and bFGF levels compared to control, reflecting enhanced angiogenic and fibroblast activity. These findings support the potential therapeutic role of phenytoin and nifedipine in wound remodelling.