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THE MRNA EXPRESSION OF SERCA AND NCX IN ACUTE PANCREATITIS MODEL UNDER MELATONIN AND TRISULFATE DISSACHARIDE ACTION
Enio R. Vasques*1, José Eduardo M. Cunha1, Marcia S. Kubrusly1, Ana Maria M. Coelho1, Sandra N. Sampietre1, Tiago Rodrigues2, Helena Nader3, Ivarne S. Tersariol3, Marcelo A. Lima3, Eleazar Chaib1, Luiz Augusto C. D'Albuquerque1 1GASTROENTEROLOGY, UNIVERSITY OF SAO PAULO MEDICAL SCHOOL, SAO PAULO, SAO PAULO, Brazil; 2FEDERAL UNIVERSITY OF ABC, SAO PAULO, Brazil; 3FEDERAL UNIVERSITY OF SAO PAULO, SAO PAULO, Brazil
Introduction: The injury of the pancreatic cells in acute pancreatitis (AP) has as precipitating factor the intracellular calcium overload, whose homeostasis depends crucially on calcium excess withdrawal by means of Plasma Membrane Calcium ATPase (PMCA), but with joint participation of Sarcoplasmic Reticulum Calcium ATPase (Serca) for calcium uptake to the sarcoplasmic reticulum, and the Sodium Calcium Exchanger (NCX) by the withdrawal of calcium to the extracellular medium. Melatonin, through its antioxidant action and cell structure and function protection and the ultra-low molecular weight heparin fragment Trisulfate Disaccharide (TD) with action on intracellular calcium withdrawal by the acceleration of sodium calcium exchanger leading to cellular protection, could influence the cellular injury determined by pancreatitis, through the protection of the structures involved in calcium homeostasis and/or decreased intracellular calcium by the acceleration of the sodium calcium exchanger. Objective: to evaluate the mRNA expression of Serca and NCX in a taurocholate model of experimental AP in Wistar rats pre-treated with melatonin and/or TD. Materials and methods: Adult male Wistar rats (n = 25) were divided into 5 groups: I-Control (no pancreatitis), II- taurocholate 3% AP, III-AP with melatonin pre-treatment, IV-TD and V-melatonin associated with the TD. In the animals treated pharmacologically, melatonin 50 mg/kg and TD 0.2 mg/kg were injected intraperitoneally 30 min and 10 minutes before AP, respectively. Pancreatic tissue samples were collected after 2 hours for the detection of mRNA levels of Serca2 and NCX1 for analysis of polymerase chain reaction. Results: There was an increase of the expression in Serca2 in the melatonin group (III), but no increase in expression of NCX. The TD did not affect levels of Serca 2 and NCX. The set treatment with melatonin and TD reduced the expression of Serca 2. Conclusion: The effect of melatonin is restricted to Serca 2 expression increase. TD has no action on gene expression, however, when associated with melatonin its action in accelerating the withdrawal of calcium exchanger can explain the slightest expression of Serca 2 by a joint action of drugs with different and possibly complementary mechanisms.
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