CHLORHEXIDINE IS an antibacterial agent that has been used extensively in recent years outside of the United States as a mouthwash for the prevention of periodontal disease. The observations of diminished plaque for mation and decreased severity of gingival inflammation have been confirmed in studies on monkeys.' Chlor hexidine also has been reported to increase the gingival healing rate following periodontal surgery, when incor porated into the periodontal dressing. Inflammatory and ulcerative lesions have been described in some pa tients using therapeutic doses of the drug as a mouth wash. However, the safety of the drug in humans has been emphasized in a number of reports, in which var ious medical parameters were found to be normal after 2 years of continuous daily use of the agent. Keratinization of palatal mucosa was found to be normal, the metabolism of oral epithelium, as determined by the activity of oxidative enzymes, was normal, and there was no evidence of inflammation or premalignant changes. The drug has been reported to be relatively nontoxic in experimental animals. Rats were able to tolerate 0.2% aqueous solutions as the only source of drinking water for periods of 6 months, with no obvious interference in growth and reproduction. Tissue culture studies, on the other hand, have demonstrated a high degree of toxic ity. 4 Exposure of human gingival fibroblasts, human newborn fibroblasts and HeLa cells to Chlorhexidine at concentrations as low as 0.004% resulted in impaired cellular function or cell death. Exposure of cells to 0.2% Chlorhexidine for 30 seconds produced suppression of protein synthesis as evidenced by release of radioactive chromium. Chlorhexidine was also found to be toxic to polymorphonuclear leukocytes, using the trypan blue dye technique. In view of the wide use of Chlorhexidine, the fact that some oral changes have been reported in humans and the absence of oral mucosal studies in experimental animals, the present study was undertaken to investigate the effect of Chlorhexidine ingestion on rat oral mucosa. The tongue was selected as the oral mucosal site of interest for several reasons. The tongue would be most likely to come in contact with the compound if delivered via the drinking water. In addition, the histol ogy of normal tongue in laboratory rats has been well described, and the organ presents two different surfaces for study. The dorsal surface is well keratinized and composed of highly specialized papillary structures, while the ventral surface is smooth and relatively nonkeratinized.
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