Objective Oxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws. Methods Arthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti–P2X7 receptor polyclonal antibody. Results Intraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune-cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells. Conclusion Oxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.

Exposure to environmental and occupational toxicants is responsible for adverse effects on human health. Chelation therapy is the only procedure able to remove toxic metals from human organs and tissue, aiming to treat damage related to acute and/or chronic intoxication. The present review focuses on the most recent evidence of the successful use of the chelating agent ethylenediaminetetraacetic acid (EDTA). Assessment of toxic-metal presence in humans, as well as the rationale of EDTA therapy in cardiovascular and neurodegenerative diseases, is reported.

Background: Resveratrol (a naturally occurring phytoalexin found in grapes and wine) has cardiovascular protective effects that suggest the antiatherogenic (ie, antiinflammatory) activities of the compound on endothelial cells. Objective: The antiinflammatory activity of resveratrol could be mediated by its interference with nuclear factor-κB (NF-κB)–dependent transcription. Thus, we studied the in vitro influence of physiologic concentrations of resveratrol (≤ 1 μmol/L) on the NF-κB signaling pathway after tumor necrosis factor α (TNF-α) stimulation of endothelial cells. Design: The effects of a 30-min (acute) and an overnight incubation of resveratrol on the nuclear appearance of p50-NF-κB and p65-NF-κB on serine and tyrosine phosphorylation of the inhibitory subunit κB α (IκBα), cytoplasmic concentrations of IκBα, NF-κB phosphorylation or nitrosylation, the reduction of the mitotic inhibitor p21, and the activation of peroxisome proliferator–activated receptor α were evaluated. Results: The nuclear appearance of p50-NFκB and p65-NFκB acutely induced by TNF-α was not modified by resveratrol but was increased after overnight incubation with resveratrol alone or in combination with TNF-α. Acute treatment with resveratrol did not modify TNF-α–induced cytoplasmic IκBα serine phosphorylation but did increase IκBα tyrosine phyophorylation. Resveratrol increased the tyrosine phosphorylation (but not nitrosylation) of immunoprecipitated NF-κB, did not decrease cellular p21, and did not increase peroxisome proliferator–activated receptor α activity. Conclusions: Acute resveratrol treatment does not inhibit the nuclear appearance of NF-κB in human umbilical vein endothelial cells, but overnight treatment does. The increase in tyrosine phosphorylation of IκBα, p50-NF-κB, and p65-NF-κB suggests the involvement of such alterations in the modulation of NF-κB transcription activity.

Neurotoxicity can be caused by numerous direct agents, of which toxic metals, organophosphorus pesticides, air pollution, radiation and electromagnetic fields, neurotoxins, chemotherapeutic and anesthetic drugs, and pathogens are the most important. Other indirect causes of neurotoxicity are cytokine and/or reactive oxygen species production and adoptive immunotherapy. The development of neurodegenerative diseases has been associated with neurotoxicity. Which arms are useful to prevent or eliminate neurotoxicity? The chelating agent calcium disodium ethylenediaminetetraacetic acid (EDTA)—previously used to treat cardiovascular diseases—is known to be useful for the treatment of neurodegenerative diseases. This review describes how EDTA functions as a therapeutic agent for these diseases. Some case studies are reported to confirm our findings.

The aetiology of neurodegenerative diseases (ND) seems to involve susceptibility genes and environmental factors. Toxic metals are considered major environmental pollutants. Following our study of a case of multiple sclerosis (MS) improvement due to removal of aluminium (Al) and other toxic metals, we have examined the possible relationship between Al intoxication and ND. We used the slow intravenous treatment with the chelating agent EDTA (calcium disodium ethylene diamine tetraacetic acid) (chelation test) to remove Al and detected it in the urine collected from the patients for 12 hours. Patients affected by MS represented 85.6% of total ND. Al was present in 44.8% of cases comprehensive of ND and healthy patients. Al levels were significantly higher in ND patients than in healthy subjects. We here show that treatment of patients affected by Al burden with ten EDTA chelation therapies (EDTA intravenous administration once a week) was able to significantly reduce Al intoxication.