Abstract
Non-steroidal anti-inflammatory drugs (NSAID) are widely used as anti-inflammatory agents, but they have serious side effects. In an attempt to reduce these side effects, a series of new compounds have been recently synthesized in which a nitric oxide (NO)-releasing group has been linked to the parent NSAID. Among them are nitro-aspirins NCX-4016 and NCX-4040. Apoptosis of inflammatory cells is a critical event in the resolution of inflammation and manipulation of the apoptosis could be of therapeutic benefit. We studied the effect of aspirin and its nitro derivatives, NCX4016 and NCX4040, on the apoptosis of the neutrophils in vivo. We used a model of inflammation by implanting polyvinyl sponges under the skin of Albino Oxford (AO) rats. Apoptosis was measured 6 and 24 hours after implantation of the sponges and application of aspirin or nitro-aspirins. Apoptosis was detected by morphological criteria after the fixation and staining the cells with Turk reagent. Also, we measured the production of NO in inflammatory exudate and in supernatants of these cells. We found that inflammatory exudate in vitro in a statistically significant manner, decreased spontaneous apoptosis as well as apoptosis induced by nitro-aspirins. In vivo the NCX4040 induced apoptosis of the neutrophils in lower concentration than NCX4016. These nitro-aspirins could be new powerful drugs for use in human and veterinary medicine.
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