Inhibition of Endotoxin-Induced Depression of Cellular Proliferation by Ascorbic Acid

Abstract

Abstract

Previous studies have shown that cementum-bound endotoxin or endotoxin-like products from untreated periodontally involved teeth depress the proliferation of, and have direct toxic effects on, cultured fibroblasts. The purpose of this investigation was to study the effect(s) of ascorbate and several other compounds on the toxicity of commercially prepared endotoxin. The 3T6 fibroblasts were grown in Dulbecco—Vogt modification of Eagles' medium containing 10% heat-inactivated calf serum. Replicate cultures were prepared and grown for 5 days. The proliferation of endotoxin-challenged cells was monitored in the presence of either l-ascorbate, d-isoascorbate, dehydroascorbate, carbonylcyanide m-chlorophenylhydrazone, or cycloheximide. Under very specific conditions, ascorbate reversed the endotoxin-mediated depression of cellular proliferation. An uncoupler of oxidative phosphorylation, carbonylcyanide m-chlorophenylhydrazone also effectively reversed the effect of endotoxin while cycloheximide had no effect. Aside from the known involvement of ascorbate in connective tissue metabolism and repair, the findings in the study suggest that acute or prolonged ascorbate deficiency may potentially compromise host defenses to endotoxin. If endotoxin is involved as one of the factors in the initiation and progression of periodontal disease, as has been suggested, the probable connection between ascorbate deficiency and periodontal disease appears to be at least twofold: primarily, in etiology; and, second, in tissue repair and return to normal function.