Efeitos do butafosfan sobre o processo inflamatório em camundongas desafiadas com endotoxina bacteriana

Abstract

Butafosfan is an organic source of phosphorus, used to improve cellular energy production, and it has been demonstrated that its use may potentiate the humoral and cellular immune response; however, the means by which it acts is still not clear. Thus, the aim of the study was to evaluate the effect of subcutaneous administration of butaphosphan on pro-inflammatory markers and neutrophil activity index in mice challenged with bacterial lipopolysaccharide. Forty-two mice were randomly divided into three groups: Butaphosphan 50 (BUT50, n=14), that received subcutaneous injections of 50 mg/kg of butaphosphan; Butaphosphan 200 (BUT200, n=14), that received subcutaneous injections of 200 mg/kg of butaphosphan and Control (CTL, n=15), that received placebo via subcutaneous. Injections were realized by eight consecutive days, twice a day, and once a day the animals were weighed. In the last experimental day, half of animals per group were randomly selected to be challenged with bacterial endotoxin (lipopolysaccharide – LPS). Two hours after the challenge animals were euthanized and blood and spleen were collected to analyze hematological parameters, circulating levels of interleukin 6 (IL-6), 1β (IL-1B) and myeloperoxidase (MPO) tissue activity. Animals of BUT200 group demonstrated reduction of body weight during the experiment (P = 0.024). Groups treated with butaphosphan, independent of dose had higher red cell count than control (P < 0.05). A marked decrease was observed in white cell count in BUT200/LPS group, as a result of 50% [decrease in neutrophil count in the same group compared to the other two challenged groups (P < 0.001). The challenge with LPS increased the concentrations of interleukin-6 (IL-6) in all groups (P < 0.001). Animals not challenged, treated with the highest butaphosphan dose had increased neutrophil (P < 0.01) and lymphocyte (P < 0.05) counts, higher IL-6 concentration (P < 0.001), and higher body temperature (P = 0.019) prior to challenge with LPS related to BUT 50 and CTL groups. The use of butafosfan in non-challenged animals was demonstrated to be positive, with increased hematopoiesis, independent of the dose used, and the increase in the circulatory pool of defense cells, IL-6 concentrations and body temperature in the group treated with the highest dose. This modulatory effect could be interesting in the prevention of situations of great immune challenge, where an increased number of inflammatory markers is important, as cancer and the transition period, in production animals. Faced with the challenge with bacterial endotoxin, the group treated with the highest dose of butafosfan maintained neutrophil levels similar to the not challenged group, reiterating the modulating effect. Thus, it is primordial that studies involving the relationship of phosphorus and immune system be enhanced, to this molecule that is present in several energetic reactions of the organisms could be directed to the improvement of the immune and general health status, both in animals and humans.