ABSTRACT
Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to prevent cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr in experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 h, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔÑ°m) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔÑ°m caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.
Subject(s)
Canavalia , Pancreatitis , Acute Disease , Animals , Anti-Inflammatory Agents , Canavalia/chemistry , Lectins/pharmacology , Male , Mice , Necrosis/drug therapy , Pancreatitis/chemically induced , Pancreatitis/drug therapy , Plant Lectins/chemistry , Seeds/chemistryABSTRACT
A mucosite intestinal é um dos efeitos adversos mais incidentes do tratamento com 5-Fluorouracil. Nesse contexto, microrganismos probióticos são cada vez mais utilizados como alternativas para proteção da mucosa gastrintestinal deste efeito colateral e distúrbios associados. Este estudo teve como objetivo avaliar o efeito de Probiotil®composto pelosprobióticos Lactobacillus acidophilus e Bifidobacterium lactis, e Probiatop® composto porLactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus rhamnosus eBifidobacterium lactis na mucosite intestinal experimental induzida por 5-FU. Para aexecução do protocolo utilizou-se camundongos machos Swiss (25-30g) que foram tratadoscom dose única intraperitoneal de 5-FU (450mg/Kg i.p.), com exceção dos controles (Salina eDMSO). Os grupos probióticos foram tratados com o Probiotil®ou Probiatop®1h, 24h e 48h(v.o.) após a indução por 5-FU, sendo eutanasiados após 72h da indução de mucosite.Segmentos do duodeno, jejuno e íleo foram obtidos para as seguintes avaliações: mensuração da relação vilo/cripta; escores histológicos; dosagem de glutationa (GSH), malondialdeído(MDA), citocinas pró-inflamatórias (TNF-α e IL-6) e atividade da enzima mieloperoxidase(MPO). Além disso, avaliou-se a análise ponderal, leucograma, esvaziamento gástrico etrânsito intestinal dos animais. Observou-se que Probiatop®diminuiu a perda de peso induzida por 5-FU, mas este efeito não foi demonstrado pelo Probiotil®...
Intestinal Mucositis is a higher adverse effects of treatment with 5-fluorouracil. In thiscontext, probiotics are widely used to protect gastrointestinal disorders. Here we report theeffect Probiotil®composed by probiotics Lactobacillus acidophilus and Bifidobacteriumlactis, and Probiatop®composed by Lactobacillus acidophilus, Lactobacillus paracasei,Lactobacillus rhamnosus and Bifidobacterium lactis in intestinal mucositis induced by 5-FU.Such methodology was used male Swiss mice (25-30g), treated with a single intraperitonealdose by 5-FU (450 mg / kg ip), and controls with(saline and DMSO). In the Probiotics groupswas administrated Probiotil®or Probiatop®1h, 24h and 48h (V.O.) after induction by 5-FU .72h after 5-FU administration, mice was euthanized. Segments from Duodenum, jejunum andileum were removed for evaluations: measurement of villous / crypt ratio; Histological scores;concentration of glutathione (GSH), malondialdehyde (MDA), proinflammatory cytokines(TNF-α and IL-6) activity and myeloperoxidase (MPO). In addition, we investigated theweight analysis, leukogram, gastric emptying and intestinal transit of animals. Our resultsshowed that Probiatop®decreased the weight loss induced by 5-FU, but Probiotil®did notchange weight loss...
