Early heart mitochondrial dysfunction in Diabetes induced by Streptozotocin

VALDEZ LB; VALDEZ LB; BOMBICINO SS; BOMBICINO SS; RUKAVINA MIKUSIC IA; RUKAVINA MIKUSIC IA

Mar del Plata

Congreso; LXI Reunión anual de SAIC, LXIV Reunión anual de SAI, XLVIII Reunión anual de SAFE, VII Reunión anual de NANOMEDAR, V Congreso Nacional de AACYTAL; 2016

SAIC, SAI, SAFE, NANOMEDAR y AACYTAL

Ventricular dysfunction in the absence of hypertension or coronary arterial disease is a complication of Diabetes Mellitus (DM) that could be associated to mitochondrial dysfunction. Results from our laboratory have shown a mitochondrial dysfunction in rat heart, 28 days after Streptozotocin (STZ)-injection, without alterations in cardiac performance in resting conditions but with a cardiac compromise against a work overload. The aim is to study early events in heart of diabetic rats concerning mitochondrial function and nitric oxide and hydrogen peroxide metabolisms, using an experimental model of type 1 DM. Diabetes was induced by a single dose of STZ (60 mg/kg, ip.) in male Wistar rats. Glycemia values after 3 days of injection were 2826 mg/dl. At 7, 10 or 15 days after STZ-injection, animals were sacrificed. Results were compared with ones obtained at 28 days after STZ administration. At 10, 15 and 28 days, the state 3 respiration sustained by malate-glutamate (30814 ng-atO/min.mg protein) or by succinate (26232 ng-atO/min.mg protein) were reduced by 20-22% or by 15-16%, respectively. Because of resting mitochondrial respiration rates were not modified in diabetic rats respect to control animals (malate-glutamate and succinate: 362 and 9512 ng-atO/min.mg protein) respiratory controls were declined. Moreover, respiratory complexes activities (I-III, II-III and IV) were significantly reduced (20-22%) at 15 and 28 days, but slightly declined (10%) at 10 days post-STZ administration. After 7 days of injection, no difference in oxygen uptake and complexes activities were detected. Thus, an incipient heart mitochondrial dysfunction was observed after 10 days of STZ administration, a process that could be triggered in response to 7 days of a sustained hyperglycemia. More studies are going to be performed at 10 days post-STZ injection, in order to study the role of nitric oxide and hydrogen peroxide as molecules involved in mitochondrial-cytosol signaling.