Imaging of cyclooxygenase-2 (COX-2) expression: potential use in diagnosis and drug evaluation.

Cyclooxygenase is an enzyme that catalyzes the first two steps in the biosynthesis of prostanoids. The constitutively expressed isoform COX-1 is regarded as a housekeeping enzyme that is responsible for the normal production of prostanoids. The inducible isoform COX-2, on the other hand, is transiently induced during inflammation by various stimuli. Increasing evidence has shown that COX-2 is not only implicated in inflammation but also in oncogenesis. Overexpression of COX-2 has been observed in a variety of tumors. Prostaglandins produced by COX-2 affect important processes in carcinogenesis, including angiogenesis, tissue invasion, metastasis and apoptosis. Several studies indicate that COX-2 is also involved in neurological disorders, like Alzheimer's disease, Parkinson's disease and ischemia, where COX-2 overexpression leads to neurotoxicity. Many aspects of the role of COX-2 in (patho)physiology, however, remain unclear. At present, COX-2 expression is determined by ex vivo laboratory analysis, but the results could be greatly affected by the instability of COX-2 mRNA and protein and by sampling errors. A noninvasive imaging method to monitor COX-2 expression, like positron emission tomography (PET) or single photon emission computed tomography (SPECT), could overcome this complication and may provide novel insights in the role of COX-2, especially in neurological disorders where repetitive sampling is not possible. Such a technique could also be applied to the in vivo evaluation of novel selective COX-2 inhibitors and in dose-escalation studies. This review will present an overview of the developments in the recently emerging field of COX-2 imaging.

Protective effect of NAC on formaldehyde-containing-ZOE-based root-canal-sealers-induced cyclooxygenase-2 expression and cytotoxicity in human osteoblastic cells.

Cyclooxygenase-2 (COX-2) is an inducible enzyme believed to be responsible for prostaglandin synthesis at 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 COX-2 expression and cytotoxicity induced by formaldehyde-containing-ZOE-based root canal sealers. The aim of this study was to investigate the effects of antioxidants such as catalase, superoxide dismutase (SOD), and N-acetyl-L-cysteine (NAC) on N2- and endomethasone-induced COX-2 mRNA gene and cytotoxicity in human osteoblastic cell line U2OS cells. Our data demonstrated that both formaldehyde-containing-ZOE-based root canal sealers 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 N2 and Endomethasone (p < 0.05). However, catalase and SOD lacked the ability to prevent cytotoxicity and COX-2 mRNA gene expression induced by N2 and Endomethasone (p > 0.05). The data presented here demonstrated that the activation of COX-2 mRNA gene expression may be one of the pathogenesis of formaldehyde-containing-ZOE-based root-canal-sealers-induced periapical inflammation. In addition, GSH depletion, but not the attack of oxygen free radicals, could be the mechanism for cytotoxicity and COX-2 mRNA gene expression induced by formaldehyde-containing-ZOE-based root canal sealers. NAC appears as a useful agent in protecting cell damage mediated by formaldehyde-containing-ZOE-based root canal sealers.