Are COX-2 Inhibitors Active on Intracellular Oxidative Processes? A Study on In Vitro and Cellular Models

Book published by Nova Science Publishers, Inc. (2006)

In the last years, there has been an increasing interest of using cyclooxygenase-2 (COX-2) inhibitors to treat the inflammatory pain and chronic inflammatory diseases such as osteoarthritis and rheumatoid ... [more ▼]

In the last years, there has been an increasing interest of using cyclooxygenase-2 (COX-2) inhibitors to treat the inflammatory pain and chronic inflammatory diseases such as osteoarthritis and rheumatoid arthritis. The beneficial effects were to avoid the secondary adverse effects such as bleeding and gastric irritation, generally observed with aspirin and conventional NSAIDs. COX-1 is constitutively expressed in most tissues and involved in the regulation of normal homeostatic functions, while COX-2 is not detected in most tissues but induced by inflammatory stimuli. These outcomes motivated the commercial development of selective COX-2 inhibitors. Recent data suggested that the COX-2 enzyme can be expressed within atherosclerotic lesions and could play a crucial role in various types of cancers, by the way of its activity on the ROS production, gene transcription and prostaglandin (PGE2) production. Consequently, the COX-2 enzyme has become a real target for the study of various classes of compounds and specially the possible additional properties of COX-2 inhibitors. We and other groups have already investigated the pro or antioxidant profile of conventional NSAIDs and some COX-2 inhibitors. With the recent withdrawal of two compounds of the coxib’s family (rofecoxib and celecoxib), for adverse cardiovascular events, concerns regarding the safety of all COX-2 inhibitors have been raised. To answer to these concerns, different approaches were developed by studying on in vitro models, the potential inhibiting-or-stimulating activities on oxidative phenomena of new drugs with already recognized therapeutic effects. Preliminary data obtained with COX-2 inhibitors showed a moderate inhibiting effect on the intracellular oxidant processes and others a stimulating activity. New hypotheses for the treatment of inflammation are now suggested for compounds like nimesulide and its analogous, which are selective towards COX-2 with little activity on COX-1. Here, we reported the in vitro effects of some Cox-2 inhibitors, in comparison with traditional drugs (ibuprofen, diclofenac and aceclofenac) by using two cellular models: a human lung type II alveolar cell line (A549) and a human promonocyte cell line (THP-1). The direct interactions between the drugs and ROS were also investigated in cell-free systems. [less ▲]

Between Invention and Innovation : the Belgian Patent System (1830-1914)

Scientific conference (2006, December 22)

L’étude de la surface des cuivreux archéologiques : apports de l’analyse par faisceaux d’ion pour la compréhension de la physico-chimie

Scientific conference (2006, December 21)

L'alimentation hivernale des bovins

Conference given outside the academic context (2006)

Characterization of potato tuber ageing using physiological markers and proteomic data based on DIGE proteome analysis and antioxidant activities assessment

Poster (2006, December 18)

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

in Brain Research (2006), 1126

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms ... [more ▼]

Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain. (c) 2006 Elsevier B.V. All rights reserved. [less ▲]

Projet CLIP (the network of European cities for local integration policies of migrants)

Scientific conference (2006, December 18)

Numérique ? Vous avez dit numérique ?

Speech (2006)

Prosopographie des médecins de l’Asie Mineure pendant l'Antiquité classique

Doctoral thesis (2006)

Autopsie d'un patient atteint de syndrome de McCune-Albright

Scientific conference (2006, December 15)