Nitric oxide (NO) regulation of C/EBP-alfa and Ref-1 in early stage of post-partial hepatectomy in streptozotocin (SZ)-induced diabetic rats

INGARAMO P I; RONCO M T; FRANCÉS D E; MONTI J A; CEBALLOS M P; CARRILLO M C; CARNOVALE C E

Congreso; VII meeting of the SFRBM-South American Group; 2011

Introduction: It is known that a decrease in liver regeneration exists in diabetes state. In previous works we showed that NO increased after partial hepatectomy (PH). We also demonstrated that it is augmented in diabetic state. The transcriptional factor C/EBPalfa may have an anti-proliferative function. Ref-1 is a protein that can regulate the redox state of diverse proteins and functions as a DNA repair endonuclease. Aim: To evaluate the NO regulation of C/EBPalfa and Ref-1 after 1 hour post-PH in liver of diabetic rats. Methodology: Adult male Wistar rats were randomized into 2 groups: control (C, citrate buffer pH=4.5, i.p.) and diabetic (D, SZ, 60 mg / kg of body weight, i.p.). Thirty days post-injection of either citrate or SZ, 10 rats of each group were subjected to PH of 70 % and were evaluated 1 h post-surgery. Five rats of each group were daily treated with 100 mg/kg body weight of aminoguanidine (AG), a selective inhibitor, on the 3 days previous to surgery (PH-C+AG and PH-D+AG). Results: Glycemia (enzymatic method, g/l): PH-C: 6,4±0,3; PH-D: 25,7±3,1*; Body weight (g): PH-C: 438±7; PH-D: 296±6*; (*p<0.05 vs. PH-C). AG did no modify these parameters. Liver NO (EPR) decreased significantly (p<0.05) in PH-C+AG (-56%) and PH-D+AG ( 39%), while it was increased (254%) in PH-D vs. PH. Western blot (as percentage of PH in total lysate): C/EBPalfa: PH-C: 100±15; PH-D: 675±58*; PH-C+AG: 279±3*†; PH-D+AG: 546±23*; Ref-1: PH-C: 100±9; PH-D: 53±8*; PH-C+AG: 281±23†*; PH-D+AG: 140±22†; *p<0.05 vs PH-C. †p<0.05 vs PH-D. Conclusion: Results indicate that diabetes increases C/EBPalfa and decreases Ref-1, and that NO exerts a key role on the regulation of both proteins 1 hour post-PH. This study may contribute to understand the mechanisms implicated in the delay of the regenerative process during diabetes.