Efeito da solução hipertônica (NaCI 7,5%) no estresse oxidativo e nos processos de morte celular e remodelamento tecidual hepático em pancreatite aguda experimental / Effect of hypertonic saline solution (NaCl 7.5%) on oxidative stress, apoptosis and hepatic tissue remodeling during acute pancreatitis




It has been shown an hepatic injury following pancreatitis and a positive correlation with severity of the disease. Hypertonic Solution (HS) reduced morbidity and mortality in experimental pancreatitis. We hypothesize that hypertonic solution resuscitation of acute pancreatitis (AP) may exert antiinflammatory effects by modulating hepatic oxidative stress, apoptosis and matrix extracellular remodeling in liver. Wistar rats were divided in four groups: C- control animals not subjected to insult or treatment; NT- subjected to pancreatitis induction and receiving no treatment; NS- subjected to pancreatitis induction and receiving normal saline (0.9% NaCl); HSsubjected to pancreatitis induction and receiving hypertonic saline (7.5% NaCl). AP was induced by retrograde infusion of 2,5% sodium taurocholate into the pancreatic duct transduodenally. At 4, 12 and 24 h following pancreatitis induction, liver tissue samples were assayed in order to analyse expression of metalloproteinases (MMPs) -2 and -9, iNOS, collagens (type I and III), Heat Shock Proteins (HSPs) 47, 60, 70 and 90, caspases -2 and -7, APAF-1 and AIF, production of the cytokines TNF-, IL-1, IL-6 and IL-10, Nitrite/nitrate and ALT, Lipid peroxidation and formation of Nytrotirosine. Hypertonic solution resuscitation significantly modulates the oxidative stress in liver by reduction of iNOS gene expression (p<0,01 vs. NS), nitrite and nitrate levels (p<0,01 vs. NS), lipid peroxidation (p<0,05 vs. NT), ALT release (p<0,01 vs. NS) and peroxinitrite inhibition after 12 hours of pancreatitis induction. Consequently, the HSP70 production has not been activated due to the hypertonic solution effect in hepatic protection. At 4 h and 12 h, MMP-9 expression and activity increased in the NS and NT groups, although remaining at basal levels in the HS group (p<0.05 vs. past, pas). At 12 h, MMP-2 expression increased in the NS group (p<0.05 vs. c) but not in the HS group. At 4 h after pancreatitis induction, HSP47 expression increased in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups than in the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. The proteins involved in apoptosis remained unchanged in all groups. Hypertonic saline is hepatoprotective, since it decreases oxidative stress in the critical time resulting in diminished liver damage, reducing hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during pancreatitis. Hypertonic saline-mediated regulation of MMP expression might have clinical relevance in pancreatitis-associated liver injury


pancreatite metalloproteases pancreatitis liver/injuries metaloproteases fígado/lesões hypertonic saline solution estresse oxidativo oxidative stress solução salina hipertônica

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