Mitochondrial H2O2 and NO are involved in early stages of cardiac mitochondrial dysfunction in a Type 1 Diabetes Mellitus model

RUKAVINA-MIKUSIC IA; VALDEZ LB; REY M

Ferrara

Congreso; SFRR-E 2019 Annual Meeting. Redox homeostsis: from signaling to damage?; 2019

Society for Free Radical Research-Europe

The aim was to study the early events that take place in heart mitochondrial dysfunction in a Type 1 DM model, in which hyperglycemia happens without the presence of insulin resistance, obesity, hypercholesterolemia and hypertension. Diabetes was induced by Streptozotocin (1 dose,60 mg/kg,ip.) in male rats (glycemia, C:130±5, DM:413±26 mg/dl). Animals were sacrificed at day 10. The state 3 O2 consumption sustained by malate-glutamate (22%) and the respiratory control (39%) were lower in heart from DM animals, in accordance with the reduction in complex I-III activity (19%). No differences in O2 uptake sustained by succinate and in complexes II-III or IV activities were observed. H2O2 (96%) and NO (25%) production rates, and NOS expression (79%) were higher in DM group. Mitochondrial [GSSG+GSH] was lower in DM rats, but there was no difference in GSH/GSSG ratio. PGC-1α expression was similar in both groups, suggesting that mitochondrial biogenesis has not been triggered yet. After 7 days of hyperglycemia, heart mitochondrial dysfunction was observed, with complex I being the only complex modified. Linear correlations between the modified mitochondrial parameters and glycemia were obtained. H2O2 and NO could be upstream molecules to de novo synthesis of mitochondria in response to hyperglycemia