RESUMO
In Colombia, Lachesis acrochorda causes 2-3% of all snake envenomations. The accidents promote a high mortality rate (90%) due to blood and cardiovascular complications. Here, the effects of the snake venom of L. acrochorda (SVLa) were analyzed on human blood cells and on cardiovascular parameters of rats. SVLa induced blood coagulation, as measured by the prothrombin time test, but did not reduce the cell viability of neutrophils and platelets evaluated by the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction assay and by the lactate dehydrogenase (LDH) enzyme assay. In fact, SVLa increased the absorbance in tests made with platelets subjected to the MTT assay. SVLa induced platelet aggregation whose magnitude was comparable to that of the positive control adenosine diphosphate (ADP), and occurred earlier with increasing SVLa concentration. Acetylsalicylic acid (ASA, a cyclooxygenase inhibitor) or clopidogrel (an ADP receptor blocker) inhibited the aggregating effect of SVLa. Inhibition of SVLa-elicited platelet aggregation also resulted from the treatment with disodium ethylenediaminetetraacetate (Na2-EDTA; metalloproteinase inhibitor) and with 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF, serine protease inhibitor). In isolated right atrium of rats, SVLa increased slightly, but significantly, the magnitude of the spontaneous contractions and, in isolated rat aorta, SVLa relaxed KCl- or phenylephrine-induced contractions. In vivo, SVLa induced hypotension and bradycardia in rats, with detection of hemorrhage in pulmonary and renal tissues. Altogether, under experimental conditions, SVLa induced blood coagulation, platelet aggregation, hypotension and bradycardia. Part of the effects presented here may be explained by the presence of snake venom metalloproteinases (SVMPs) and snake venom serine proteases (SVSPs), constituents of SVLa.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Venenos de Víboras/toxicidade , Viperidae , Animais , Células Sanguíneas , Coagulação Sanguínea , Plaquetas , Colômbia , Fibrinogênio , Hemorragia , Humanos , Hipotensão , Metaloproteases , Agregação Plaquetária , Tempo de Protrombina , Ratos , Serina Endopeptidases , Serina Proteases , Inibidores de Serina Proteinase , Mordeduras de SerpentesRESUMO
NEW FINDINGS: What is the central question of this study? Is the responsiveness of isolated segments of the rat oesophagus to contractile or relaxant stimuli susceptible to acute luminal exposure of the oesophagus to an acid solution that contains pepsin and bile salt? What is the main finding and its importance? The study reveals that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophageal body, even in the absence of inflammation. ABSTRACT: We investigated whether the experimental simulation of duodenogastro-oesophageal reflux alters the contractile responsiveness of rat oesophageal strips. After 30 min of luminal exposure to a solution at acid pH that contained pepsin and taurodeoxycholic acid, isolated strips of the rat oesophagus and gastro-oesophageal junction were subjected to contractile or relaxing stimuli. Acid challenge decreased the responsiveness of oesophageal strips to contractile stimulation, especially in oesophageal preparations that were mounted following the circular orientation of the muscularis externa layer. The contractility of longitudinal preparations of the rat oesophagus appeared less susceptible to the deleterious effects of acid challenge. In contrast, the responsiveness of ring-like preparations from the gastro-oesophageal junction to contractile stimulation was unaltered by acid challenge. Taurodeoxycholic acid decreased the responsiveness of circular oesophageal preparations to KCl, an effect that was exacerbated by luminal acidity. On the contrary, although the relaxant ability of the rat oesophagus did not change, acid challenge increased the relaxant efficacy of sodium nitroprusside and isoprenaline in strips of the gastro-oesophageal junction. A significant decrease in transepithelial electrical resistance was seen when the oesophageal mucosa was challenged at pH 1 but not at pH 4. Treatment with alginate blunted the deleterious effects of acid challenge on transepithelial electrical resistance and the responsiveness of oesophageal preparations to KCl. The present findings support the notion that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophagus.