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Aged-Depend Vulnerability to Experimental Acute Pancreatitis Is Associated With Previous Liver Mitochondrial Damage
ANA Maria M. Coelho*, Sandra N. Sampietre, Marcel C. Machado, José Eduardo M. Cunha, Eleazar Chaib, Luiz Augusto C. D'Albuquerque
Gastroenterology, University of Sao Paulo, Sao Paulo, Brazil
Introduction/Background: It has been widely accepted that the functional impairment of mitochondria is central to the multifactorial process of ageing. Acute pancreatitis (AP) in elderly patients in spite of similar occurrence of local complications is followed by a substantial increase in multiple organ failure, including liver failure. We have previously demonstrated a disruption of liver mitochondrial function in rats with AP. However, studies of the effects of ageing on liver mitochondrial function after AP induction have not been previously reported. The aim of the present study was to evaluate the effect of ageing on liver mitochondrial function after AP induction.
Methods: Wistar rats were divided into two groups: Young (3 months old rats, n= 20) and Aged (18 months old rats, n= 20). Both groups were subdivided into two experimental groups: (1) Sham group: rats submitted to the operative procedure without induction of AP and (2) AP group. AP was induced by intraductal 2.5% taurocholate injection. Two hours after AP or sham-operation, blood samples were collected for determinations of amylase, AST and ALT. Liver tissue was evaluated for mitochondrial function and malondialdehyde (MDA) content. Mitochondrial oxidation and phosphorylation were measured polarographically by determining oxygen consumption.
Results: A significant increase in serum amylase, AST, ALT was observed in the Aged group compared to the Young group (p<0.05). Two hours after AP a transient liver mitochondrial dysfunction occurred in young animals, mainly due to uncoupling of oxidative phosphorylation, and that was partially recovered. Liver mitochondrial dysfunction did not occur in the Sham group of young animals. However, in aged animals two hours after AP there was a liver mitochondrial dysfunction that was also noted in sham aged animals, suggesting a previous degenerative process similar to that found in cellular ischemia. Likewise, it was observed an increase of MDA content in young animals two hours after AP in comparison to the sham group. The aged animals showed an increase of MDA content both in the sham group and in the AP group.
Conclusion: This study demonstrates that liver mitochondrial function is transiently compromised in young animals submitted to AP. However, in aged animals unexpectedly the pre-existing severe mitochondrial dysfunction remained unchanged after induction of AP associated with a sustained oxidative stress. These findings may have significant therapeutic implications in the clinical setting.
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