Effects of chlorpromazine on alveolar bone loss in experimental periodontal disease in rats

Chlorpromazine (CPZ), a phenothiazine derivative, possesses anti-inflammatory properties, inhibition of tumor neurosis factor-alpha (TNF-alpha) synthesis and bone resorption. TNF-alpha promotes inflammatory changes and bone resorption in periodontitis. We have studied the effect of CPZ in experimental periodontitis. Wistar rats were subjected to a ligature placement around the cervix of the right second upper molars. Alveolar bone loss was evaluated by the sum of the distances between the cusp tip and the alveolar bone along the axis of each molar root, which was subtracted from the contralateral side. Histopathological analysis of the periodontium was based on cell influx, osteoclast number, and alveolar bone and cementum integrity. Animals were weighed daily and total and differential peripheral white blood cell counts were performed 6 h and 1, 7 and 11 d after periodontitis induction. Groups were treated with CPZ 1 h before and daily up to the 11th d of periodontitis. Alveolar bone loss was inhibited 46%, 55.4%, and 76.5% by CPZ at 1, 3 and 9 mg/kg, respectively. Histological analysis showed a significant reduction of cell influx and osteoclast number, as well as preservation of the alveolar process and cementum. CPZ reversed leukocytosis but not weight loss. In conclusion, CPZ reduces bone loss in experimental periodontitis, probably via TNF-alpha blockade.