Effect Of Buflomedil On The Neutrophil-Endothelial Cell Interaction Under Inflammatory And Hypoxia Conditions

Abstract

In hypoxia/ischaemia and ischaemia/reperfusion, human neurophils are likely to play an important role in the development of endothehal cell damage in the microcirculation. Buflomedil hypochloride improves the capillary perfusion in such related situations, evoking a possible effect upon neutrophils. Using in vitro models of cell adhesion, buflomedil decreased 100% of histamin related neutrophil adhesion (flow sytem) and partially inhibited adhesion after IL-1–4 hours (flow and stable systems). Hypoxia induced neutrophil adhesion (4 hours) was also reduced by buflomedil, which decreased the expression of P-selectin at the surface of endothehal cells. As adenosin (NECA) exhibited the same results in hypoxia and theophylline inhibited them, such results support an action of buflomedil presumably via the A2 receptor.

Protective Effect of Buflomedil in a Rat Model of Moderate Cerebral Ischemia

“…Recently, Capecchi and coworkers [30] reported that buflomedil infusion increases plasma levels of adenosine and adenine nucleotides in humans, very likely through an enhanced release (rather than a cell uptake inhibition) of adenosine. Moreover, Boisseau and coworkers [4] demonstrated that the buflomedil-induced reduction in neutrophil adhesion following hypoxia is very likely mediated by activation of the A 2 receptor. Adenosine has been shown to be a sensitive indicator of cerebral ischemia and a modulator of cerebral perfusion.…”

“…Furthermore, in vitro studies on human neutrophils showed that buflomedil reduces aggregation, pseudopod formation, adhesion and degranulation of lisosomial enzymes. Boisseau and coworkers [4] report that buflomedil reduces hypoxia-induced neutrophil adhesion and P-selectin expression at the endothelial cell surface, suggesting that the drug acts through the A 2 receptor. Moreover, in a porcine model of hyperdynamic endotoxemia, buflomedil proved to be able to suppress systemic activation of circulating and emigrated polymorphonuclear leukocytes [5].…”

Acceleration of wound healing by topical drug delivery via liposomes

“…A variety of therapeutic regimes have therefore been investigated in experimental and clinical settings for improvement of microvascular perfusion and acceleration of wound healing [3,4,5,6,7,8,9]. Buflomedil hydrochloride has been shown to ameliorate microcirculation, probably due to its vasodilatory and rheological properties [10,11,12,13] and, consequently, wound healing [14]. However, oral and parenteral application of drugs can be accompanied by the risk of serious side effects or the disadvantage of early inactivation of the drug.…”