ABSTRACT
BACKGROUND AND OBJECTIVES: Serious functional and structural alterations of gastrointestinal tract are observed in failure of blood supply, leading to gastrointestinal dismotility. Activation of opioid receptors provides cardioprotective effect against ischemia-reperfusion (I/R) injury. The aim of the present study was to determine whether or not remifentanil could reduce I/R injury of small intestine. METHODS: Male Wistar Albino rats were subjected to mesenteric ischemia (30 min) followed by reperfusion (3 h). Four groups were designed: sham control; remifentanil alone; I/R control; and remifentanil + I/R. Animals in remifentanil + I/R group were subjected to infusion of remifentanil (2 ug kg-1 min-1) for 60 min, half of which started before inducing ischemia. Collecting the ileum tissues, evaluation of damage was based on contractile responses to carbachol, levels of lipid peroxidation and neutrophil infiltration, and observation of histopathological features in intestinal tissue. RESULTS: Following reperfusion, a significant decrease in carbachol-induced contractile response, a remarkable increase in both lipid peroxidation and neutrophil infiltration, and a significant injury in mucosa were observed. An average contractile response of remifentanil + I/R group was significantly different from that of the I/R group. Lipid peroxidation and neutrophil infiltration were also significantly suppressed by the treatment. The tissue samples of the I/R group were grade 4 in histopathological evaluation. In remifentanil + I/R group, on the other hand, the mucosal damage was moderate, staging as grade 1. CONCLUSIONS: The pretreatment with remifentanil can attenuate the intestinal I/R injury at a remarkable degree possibly by lowering lipid peroxidation and leukocyte infiltration.
JUSTIFICATIVA E OBJETIVOS: Alterações funcionais e estruturais sérias do trato gastrointestinal são observadas na insuficiência de irrigação sanguínea, levando a alterações da motilidade gastrointestinal. A ativação dos receptores opioides proporciona um efeito cardioprotetor contra a lesão de isquemia/reperfusão (I/R). O objetivo do presente estudo foi determinar se remifentanil pode ou não reduzir a lesão de I/R do intestino delgado. MÉTODOS: Ratos machos albinos, da linhagem Wistar, foram submetidos à isquemia mesentérica (30 minutos) seguida de reperfusão (3 horas). Quatro grupos foram designados: sham controle; remifentanil isolado; controle I/R; remifentanil + I/R. Os animais do grupo remifentanil + I/R foram submetidos à infusão de remifentanil (2 µg kg-1 min-1) por 60 min, metade dos quais iniciou antes da indução da isquemia. Coletando os tecidos do íleo, a avaliação dos danos foi baseada nas respostas contráteis ao carbacol, nos níveis de peroxidação lipídica e infiltração de neutrófilos e na observação das características histopatológicas no tecido intestinal. RESULTADOS: Após a reperfusão, uma diminuição significativa da resposta contrátil induzida por carbacol, um notável aumento tanto da peroxidação lipídica quanto da infiltração de neutrófilos e uma lesão significativa da mucosa foram observados. A média da resposta contrátil no grupo remifentanil + I/R foi significativamente diferente daquela do grupo I/R. A peroxidação lipídica e a infiltração de neutrófilos também foram significativamente suprimidas pelo tratamento. As amostras de tecido do grupo I/R apresentaram grau 4 na avaliação histopatológica. No grupo remifentanil + I/R, por outro lado, a lesão da mucosa foi moderada, apresentando estadiamento de grau 1. CONCLUSÕES: O pré-tratamento com remifentanil pode atenuar a lesão intestinal de I/R em um grau notável, possivelmente pela redução da peroxidação lipídica e da infiltração leucocitária.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease/physiopathology , Disease Progression , Cognitive Dysfunction/physiopathology , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Diagnostic Self Evaluation , Longitudinal Studies , Massachusetts , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Prognosis , Proportional Hazards Models , RiskABSTRACT
Background: To shed some light on full characterization and utilization of nonsteroidal anti-inflammatory drugs (NSAIDs) in veterinary medicine, this study, therefore, was designed to clarify the pharmacological effects of two NSAIDs (one selective, that is meloxicam, and the other is non-selective, that is piroxicam) on intestinal contractility of rabbit as a farm animal species. Methods: Rabbits were humanely slaughtered, and segments from different parts of intestinal tracts were dissected out and an intestinal segment of about 2 cm long was fixed in an organ bath containing warm oxygenated Tyrode’s solution at 37°C. The tissue was subjected to a resting tension of 2 g and allowed to equilibrate for 30 min and then the effects of graded increased concentrations of piroxicam and meloxicam were demonstrated on the normal rhythmic motility of the isolated intestinal segments. The sites of action of piroxicam and meloxicam were tried. Results: Piroxicam and meloxicam exhibited concentration-dependent relaxations of intestinal smooth muscle segments with minimal and maximal effects of more potency by prioxicam than meloxicam. Calculated inhibitory concentration 50% were 15.45 and 23.10 μg/ml bath for piroxicam and meloxicam, respectively. Effects of either piroxicam or meloxicam did not involve cholinergic, adrenergic, histaminergic, nitrergic, or purinergic pathways as the application of the corresponding agonists/ antagonists did not affect the inhibitory response of piroxicam and meloxicam. It was assumed that the effects of the drugs were attributed to the direct effects of the drugs on the intestines in addition to inhibiting endogenous prostaglandin synthesis activity via their cyclo-oxygenase inhibiting properties. Conclusions: Data of the present study may indicate that piroxicam and meloxicam could be used effectively and safely in rabbits for their anti-inflammatory actions in small therapeutic doses. However, in large doses, they (particularly, piroxicam) may produce depressant effects on gastrointestinal tract motility that should be taken in consideration in the case of introducing these drugs in therapy with larger doses.