Proliferative Activity in Ischemia/Reperfusion Injury in Hepatectomized Mice: Effect of N-Acetylcysteine

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Silva, S. M.
Carbonel, Adriana Aparecida Ferraz [UNIFESP]
Taha, Murched Omar [UNIFESP]
Simoes, M. J.
Montero, Edna Frasson de Souza [UNIFESP]
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Background. Dysfunction of the liver after transplantation may be related to the graft size and ischemia/reperfusion (I/R) injury. N-Acetylcysteine (NAC) exerts beneficial effects on livers undergoing ischemia reperfusion. We sought to evaluate NAC modulation on reduced livers associated with I/R injury.Methods. Male C57BL/6 mice of 8 weeks of age were divided into groups: 50% hepatectomy (G-Hep); NAC (G-Hep + NAC [150 mg/kg]) via vena cava 15 minutes before hepatectomy; ischemia (G-Hep + IR); NAC with hepatectomy (G-IR + Hep + Nac); and IR using 30 minutes selective hepatic occlusion and reperfusion for 24 hours. After 24 hours, the remaining liver was removed, for staining with hematoxylin and eosin or labeling by proliferating cell nuclear antigen. Blood was collected for biochemical evaluations. Significance was considered for P <= .05.Results. Aspartate aminotransferase was high in all studied groups reflecting the hepatectomy and intervention. injuries. However, when assessing alanine aminotransferase, which depicts liver function, induction of IR promoted a greater increase than hepatectomy (P = .0003). NAC decreased ALT activity in all groups, even in association with I/R (P < .05), reflecting a modulation of the injury. Necrosis resulting from IR was mitigated by NAC. the experimental model of 50% reduced live promoted regeneration of the hepatic remnant, which was accentuated by NAC, according to the total number of hepatocytes and PCNA values.Conclusion. NAC preserved the remnant liver in mice and stimulates regeneration even after IR injury.
Transplantation Proceedings. New York: Elsevier B.V., v. 44, n. 8, p. 2321-2325, 2012.