Hepatic increases of microsomal lipid peroxidation (LPO), mitochondrial pro-apoptotic protein (Bax) and cytosolic cytochrome c (cyt c) in early stages of regeneration after partial hepatectomy (PH) in diabetic rats.

FRANCÉS, DANIEL; RONCO, MARÍA TERESA; MONTI, JUAN ALBERTO; QUIROGA, ARIEL DARÍO; PARODY, JUAN PABLO; ALVAREZ, MARÍA DE LUJÁN; CARRILLO, MARÍA CRISTINA; CARNOVALE, CRISTINA ESTER

Montevideo, Uruguay

Congreso; V Meeting of SFRBM. South American Group. V Internacional Conference on Peroxinitrite and Reactive Nitrogen Species.; 2007

Society of Free Radicals Biology and Medicine

Introduction: In diabetes has been observed a retard in the liver regeneration. In prior studies we showed that the hepatic LPO plays an important role in the early stages of the liver regeneration process. Objective: Analyze the levels of LPO, the percentage of oxidized glutathione (%GSSG) and the balance of the pro-apoptotic (Bax) and anti-apoptotic (Bcl-xL) proteins in the first hours post-hepatectomy in diabetic rats. Methods: Male Wistar adult rats were divided into two groups: Control (C) (n=20), injected i.p. with buffer citrate pH=4.5 and Diabetic (D) (n=20) injected i.p. with streptozotocin (SZ) 60mg/kg b.w. After 15 days the groups were subdivided in: Control (c, no surgery), Sham (Sh, surgery simulated) and Hepatectomized (PH, hepatectomy of the 65%). The animals of all subgroups were sacrificed 1 (1) and 5 hours (5) post-surgery. Results: Blood glucose (g/l): C=1.1±0.1; D=4.3±0.4*. Insulin (Radio immuno assay, UI/ml): C=59.6±3.1; D=38.4±2.9*. LPO (Ohkawa method, nmol of malondialdehyde/mg of prot.): Cc=0.63±0.28; CHP1=0.97±0.34*; CHP5=0.94±0.30*; Dc=1.28±0.54*; DHP1=2.01±0.38; DHP5=0.98±0.39*. Cytosolic GSSG (Tietze method, %): Cc=6.4±0.7; CHP1=12.7±1.6*; CHP5=10.6±0.7*; Dc=11.4±0.5*; DHP1=11.2±0.2*; DHP5=8.1±0.7. Mitochondrial Bax protein levels (Western Blot) showed significant increases vs. Cc (100%): CHP1=32%*; CHP5=60%*; Dc=76%*; DHP1=97%*; DHP5=79%*. Mitochondrial Bcl-xL protein levels (Western Blot) showed significant increases vs. Cc (100%): CHP5=76%*; Dc=40%*; DHP1=18%; DHP5=107%*#. Cytosolic Cytochrome c protein levels (Western Blot) showed significant increases vs. Cc (100%): CHP1=19%*; CHP5=81%*; Dc=124%*; DHP1=140%*; DHP5=300%*#. (*p<0.05 vs. Cc; #p<0.05 vs. Dc). Not differences in the levels of the parameters studied between the subgroups c and Sh existed in C as in D groups. Conclusion: The high production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) responsible for the LPO, are seen enlarged in the diabetic basal state (Dc). This would be able to explain that be erased the fine regulation that exert ROS and RNS on Bax and Bcl-xL proteins in the early stages of the liver regeneration in the diabetic state.