Hyperglycemia Induces Apoptosis in Rat Liver Through Hydroxyl Radical (OH·) Increase. New Insight in Insulin Effect.

FRANCÉS D. E.; RONCO M. T.; MONTI J. A.; INGARAMO P. I.; PISANI G. B.; PARODY J. P.; PELLEGRINO J. M.; CARRILLO M. C.; CARNOVALE C. E.

Santiago

Congreso; Free Radicals and antioxidants in Chile; 2009

SFRBM-South American Group

Hyperglycemia-derived oxygen free radicals are mediators of diabetic complications. Aim: We analyzed liver apoptosis through the bax-caspase pathway in hyperglycemia and the contribution of HO·. Experimental procedures: Male adult Wistar rats were randomized in 5 groups: control (C) (citrate buffer, ip), streptozotocin (STZ)-induced diabetic (D) (STZ 60mg/kg bw, ip), insulin-treated D (D+I) (15 days post-STZ injection, D received insulin s.c., three times a day, 15 days). Desferoxamine-treated (D+DES) (100mg/kg bw, ip, 15 days) and Tempol-treated (D+TEMP) (20mg/kg bw, iv, 15 days). Rats were autopsied on day 30. Results: D showed a significant increase (56%) in liver HO· production (as 2,3-dihydroxybenzoic acid/Salicylic Acid ratio, HPLC) which correlated with lipid peroxidation levels (MDA). Besides, HO· significantly increase mitochondrial Bax/Bcl-xL proteins ratio (270%), cytosolic cyt c levels (120%), and caspase-3 activity (40%) leading to an increase in apoptosis index (170%) (p