The in vitro cytotoxicity of
sanguinarine chloride, a dental product used in the treatment of
gingivitis and plaque, was compared using cell lines and primary cells from oral human tissues. For the established cell lines,
sanguinarine chloride exhibited similar potencies to S-G gingival epithelial cells and to KB
carcinoma cells, whereas HGF-1 gingival fibroblasts were more tolerant. However, a gingival primary cell culture was more sensitive to
sanguinarine chloride than were the established cell lines. Detailed studies were performed with the S-G cells. The 24-hr midpoint (NR50) cytotoxicity value towards the S-G cells was 7.6 microM, based on the
neutral red cytotoxicity assay; vacuolization and multinucleation were noted. When exposed to
sanguinarine chloride for 3 days, a lag in growth kinetics was first observed at 1.7 microM. Damage to the integrity of the plasma membrane was evident, as leakage of
lactic acid dehydrogenase occurred during a 3 hr exposure to
sanguinarine chloride at 0.1275 mM and greater. The cytotoxicity of
sanguinarine chloride to the S-G cells was lessened in the presence of an S9 hepatic microsomal fraction from
Aroclor-induced rats or by including
fetal bovine serum (15%) in the exposure medium. Progressively increasing the pH from 6.0 to 7.8 enhanced the potency of
sanguinarine chloride, presumably due to the enhanced uptake of the lipophilic alkanolamine form, as compared to that of the cationic iminium form.