Cyclooxygenase-2 (COX-2) is an inducible enzyme believed to be responsible for prostaglandin synthesis at the site of inflammation. Recently, the activation of COX-2 expression may be one of the important pathogenesis of root canal sealers-induced periapical inflammation. However, little is known about whether chemical interaction can modulate the epoxy resin-based root canal sealers-induced cytotoxicity as well as COX-2 expression. The aim of the present study was to investigate the effects of antioxidants catalase, superoxide dismutase (SOD), and N-acetyl-L-cysteine (NAC) on AH26- and Topseal-induced COX-2 mRNA gene and cytotoxicity in human osteoblastic cell line U2OS cells. The results showed that both epoxy resin-based root canal sealers were cytotoxic to U2OS cells in a concentration-dependent manner (p<0.05). AH26 and Topseal were found to induce COX-2 mRNA gene expression in U2OS cells. The addition of glutathione (GSH) precursor NAC led to decrease the induction of COX-2 mRNA gene expression and cytotoxicity by both AH26 and Topseal (p<0.05). However, catalase and SOD lacked the ability to prevent AH26-and Topseal-induced cytotoxicity and COX-2 mRNA gene expression (p>0.05). Taken together, the activation of COX-2 mRNA gene expression may be one of the pathogenesis of epoxy resin-based root canal sealers-induced periapical inflammation. In addition, GSH depletion, but not the attack of oxygen free radicals, could be the mechanism for epoxy resin-based root canal sealers-induced cytotoxicity and COX-2 mRNA gene expression. Factors that induce GSH synthesis may appear useful in preventing cell damage mediated by epoxy resin-based root canal sealers.
