Activation of peroxisome proliferator-activated receptor (PPAR) by pioglitazone in oral traumatic ulcers in female rats

This study aimed to evaluate the effect of pioglitazone treatment on oral ulcer healing in rats, given its potential to modulate inflammatory processes. Thirty-two animals were randomly allocated into four groups: one control and three treated with different doses of pioglitazone (5, 15, and 45 mg/kg). Oral mucosal ulceration was induced one hour after treatment using a 6 mm diameter and 1 mm deep punch. Samples were collected on days 1, 3, 7, and 14 for histological analysis with optical microscopy, while immunohistochemistry was performed to assess expression of inflammatory markers across five fields. Ulcer size significantly decreased in groups treated with 15 and 45 mg/kg compared with the control group on days 1, 3, and 7. By day 14, no differences were observed between groups, although all groups exhibited progressive reduction from day 7 onward. Histological scoring demonstrated reduced acute inflammation in pioglitazone-treated animals by day 3, evolving into mild inflammation by day 7 and minimal levels by day 14. Additionally, Pioglitazone treatment also reduced TNF-α, IL-6, and NFkB p65 levels compared to controls. This study demonstrates that pioglitazone accelerates oral healing by modulating inflammatory mediators, suggesting a novel therapeutic role in wound management.