The m-rna, expression of serca2 and ncx1 in the process of pharmacological cell protection in experimental acute pancreatitis induced by taurocholate / Expressão do rna-m, da serca2 e do ncx1 no processo de proteção celular farmacológica na pancreatite aguda experimental induzida por taurocolato

ABSTRACT Background: Intracellular calcium overload is known to be a precipitating factor of pancreatic cell injury in acute pancreatitis (AP). Intracellular calcium homeostasis depends of Plasmatic Membrane Calcium ATPase (PMCA), Sarcoplasmic Endothelial Reticulum Calcium ATPase 2 (SERCA 2) and the Sodium Calcium Exchanger (NCX1). The antioxidant melatonin (Mel) and Trisulfate Disaccharide (TD) that accelerates NCX1 action could reduce the cell damage determined by the AP. Aim: To evaluate m-RNA expressions of SERCA2 and NCX1 in acute pancreatitis induced by sodium taurocholate in Wistar rats pre-treated with melatonin and/or TD. Methods: Wistar rats were divided in groups: 1) without AP; 2) AP without pre-treatment; 3) AP and Melatonin; 4) AP and TD; 5) AP and Melatonin associated to TD. Pancreatic tissue samples were collected for detection of SERCA2 and NCX1 m-R NA levels by polymerase chain reaction (PCR). Results: Increased m-RNA expression of SERCA2 in the melatonin treated group, without increase of m-RNA expression of the NCX1. The TD did not affect levels of SERCA2 and NCX1 m-RNA expressions. The combined melatonin and TD treatment reduced the m-RNA expression of SERCA2. Conclusions: The effect of melatonin is restricted to increased m-RNA expression of SERCA2. Although TD does not affect gene expression, its action in accelerating calcium exchanger function can explain the slightest expression of SERCA2 m-RNA when associated with Melatonin, perhaps by a joint action of drugs with different and but possibly complementary mechanisms.

RESUMO Racional: A lesão celular da pancreatite aguda (PA) envolve sobrecarga de cálcio, regulada pela atividade da Cálcio ATPase de membrana (PMCA), Cálcio ATPase do Retículo (SERCA2) e pelo Trocador Sódio Cálcio (NCX1). A melatonina (antioxidante) e o Dissacarídeo Trissulfatado (acelerador do NCX1) poderiam reduzir a lesão celular na PA. Objetivo: Avaliar a expressão do RNAm da SERCA2 e NCX1 em modelo animal de pancreatite aguda tratados com melatonina e/ou dissacarídeo trissulfatado (DT). Método: Ratos Wistar foram divididos em grupos: 1) sem pancreatite aguda; 2) com pancreatite aguda por taurocolato; 3) PA e Melatonina; 4) PA e DT; 5) PA e Melatonina com DT. Amostras de tecido foram colhidas para detecção dos níveis de RNAm da SERCA2 e NCX1 por PCR. Resultados: Houve aumento da expressão do RNAm da SERCA2 no grupo com PA tratados com Melatonina, porém sem aumento de expressão do NCX1. O DT não afetou os níveis de SERCA2 e NCX1. O tratamento conjunto com Melatonina e DT diminuiu a expressão da SERCA2. Conclusões: O efeito da Melatonina é restrito ao aumento da expressão da SERCA2. O DT não tem ação na expressão gênica, porém sua ação na aceleração do trocador na retirada do cálcio pode explicar a menor expressão da SERCA2 quando associado à Melatonina, pela ação conjunta de drogas com mecanismos diferentes e possivelmente complementares.

Metabolic analysis of the effect of rheum on a taurocholate-induced acute pancreatitis rat model

ABSTRACT The effects of rheum on serum parameters in a taurocholate-induced acute pancreatitis (AP) rat model were investigated using pathological and biochemical tests, and a proton nuclear magnetic resonance (1H NMR)-based metabonomic strategy. Healthy rats and rats with AP were either treated with rheum (7.5% at a dose of 1.5 g/kg) or left untreated. Serum samples were collected from the AP and rheum-treated groups at 6, 12, and 24 h after treatment. The effect of rheum on pathological changes in the pancreatic was investigated to validate the AP model. We obtained 1H NMR spectra and analyzed the results using the partial least squares discriminant method. The results of the pathological and metabolic analyses revealed an amelioration of multiple metabolic abnormalities and an increase in the aerobic respiration ratio after treatment, compared with the AP groups. These results were attributed to improvements in energy supply and the elimination of metabolic products. The study also promoted NMR-based metabonomic analysis as a feasible method of assessing traditional Chinese drugs.

Estudo da celularidade do parenquima pulmonar distal em ratos pelo metodo do lavado bronco-alveolar na pancreatite aguda / A study of the distal pulmonary cells obtained by broncho alveolar lavage in rats with acute pancreatitis

Alteracoes celulares do lavado bronco-alveolar (LBA) em ratos com pancreatite aguda necro-hemorragica (PANH) foram estudadas nos tempos de duas e oito horas apos indicao de PANH por injecao de solucao de acido taurocolico a 2,5 por cento no ducto hepatico. Grupo controle-dez ratos, Grupo PANH-nove ratos (2hs) Grupo PANH (8hs)-oito ratos. A comparacao entre os grupos mostrou aumento significativo no numero de Macrofagos/ml, segmentados/ml e linfocitos/ml no LBA (p<0,05). Assim os autores concluem que a PANH aumenta o numero de celulas inflamatorias principalmente dos neutrofilos segmentados no LBA de ratos o que e compativel com uma pneumopatia inflamatoria aguda