Background and Objectives: This study aimed to evaluate the association between systemic nicotine administration and histological and biochemical repair endpoints in an acetic acid-induced rat oral ulcer model. Materials and Methods: Thirty-six male Wistar rats were assigned to control, oral ulcer + saline, and oral ulcer + nicotine (1 mg/kg/day, s.c.) groups. Oral ulcers were induced with 70% acetic acid. After 15 days, buccal mucosa and plasma samples were collected for histopathological and biochemical analyses. Epithelial thickness and fibrosis were assessed histologically, while malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor-A (VEGF-A), and epidermal growth factor receptor (EGFR) were quantified. Results: Relative to controls, ulcer induction was associated with reduced epithelial thickness and increased fibrosis, MDA, and TNF-α levels. Compared with the oral ulcer + saline group, the nicotine-treated group showed greater epithelial thickness, lower fibrosis, lower MDA and TNF-α levels, and higher VEGF-A and EGFR levels at the study endpoint. No significant difference in VEGF-A was observed between the control and oral ulcer + saline groups. Conclusions: In this acetic acid-induced rat model, systemic nicotine administration was associated with improved endpoint histological and biochemical indices of oral ulcer repair. Because macroscopic wound closure, dose–response relationships, route comparisons, and direct mechanistic experiments were not included, these findings should be interpreted as preliminary preclinical associations rather than evidence of a direct causal effect of nicotine on wound healing.
Acu et al. (2026) studied this question.