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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effects of sarpogrelate on superoxide production by human neutrophils.

BACKGROUND AND OBJECTIVES: Superoxide anion (O2-) released from neutrophils plays an important role in antibacterial host defense system and tissue auto-injury. Sarpogrelate, a serotonin-receptor antagonist, has been successfully used for management of chronic pain caused by arterial occlusive or ischemic vascular diseases, or by microcirculation disturbances. Suppression of O2- generation may be detrimental to infection or contribute to the therapeutic approach to these diseases, the pathogenesis of which probably includes neutrophil activation. No data regarding the effects of sarpogrelate on neutrophil functions are available despite the possible clinical concern. The purpose of this study was to determine whether sarpogrelate reduces O2- production by human neutrophils using an in vitro system. In addition, we examined changes in concentrations of the intracellular calcium ion ([Ca2+]i), which is responsible for one of the mechanisms of the neutrophils' O2- production. METHODS: The O2- production by human neutrophils or the xanthine-xanthine oxidase system and [Ca2+]i were measured in the absence and the presence (at clinically relevant concentrations: 0.1x, 10x, and 100x these concentrations) of sarpogrelate. RESULTS: Sarpogrelate inhibited O2- production of neutrophils in a dose-dependent manner. The drug at a clinically relevant concentration suppressed this neutrophil function. In contrast, sarpogrelate failed to inhibit O2-generation by the cell-free (xanthine-xanthine oxidase) system. Elevation of [Ca2+]i in neutrophils stimulated by a chemotactic factor was dose-dependently attenuated with sarpogrelate. CONCLUSIONS: These findings suggest that sarpogrelate (even at clinically relevant concentrations) is able to inhibit O2- production by neutrophils. However, the drug failed to quench an excessive amount of O2- (similar to the level produced by neutrophils). There is a possibility that the inhibitory effect of the drug on [Ca2+]i response in neutrophils may contribute to impairment of the neutrophils' O2- production. Further studies using in vivo systems are required to elucidate the inhibitory effects of sarpogrelate on O2- in clinical settings.[1]


  1. The effects of sarpogrelate on superoxide production by human neutrophils. Mikawa, K., Akamatsu, H., Nishina, K., Shiga, M., Maekawa, N., Obara, H., Niwa, Y. Regional anesthesia and pain medicine. (2000) [Pubmed]
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