DIABETIC EMBRYOPATHY: ADDRESSING THE EFFECT OF A MITOCHONDRIAL ANTIOXIDANT

HIGA R, ROBERTI S, MAZZUCCO MB, WHITE V, JAWERBAUM A

Málaga

Congreso; 47 th Annual Meeting of the Diabetes Pregnancy Study Group (DPSG); 2015

A pro-oxidant intrauterine environment has been involved in the embryo damage induced by maternal diabetes even in mild experimentalmodels of this metabolic disease. The mitochondrion is the main source ofreactive oxygen species in different tissues. Aiming to address whether mitochondrial-induced oxidative stress is involved in diabetic embryopathy, weanalyzed the effect of maternal treatments with idebenone (a mitochondrial antioxidant) in pro-oxidant and pro-inflammatory pathways on E10.5 embryos fromcontrol and mild diabetic rats. A pregestational model of mild diabetes was inducedby neonatal streptozotocin administration (90 mg/dl). Maternal treatments with idebenone(100 mg/kg, oral treatment) or vehicle (water) were performed from day 1 to10.5 of gestation. Embryos were explanted and preserved for the evaluation of theexpression of genes involved in redox balance (NRF2, MnSOD), in the pro-inflammatorystate (TNFalpha) and in mitochondrial biogenesis and function (NRF1, PGC-1alpha). Inaddition, protein expression of the mitochondrial protein COX-IV was immunolocalized, peroxynitrite-induced damage was evaluated by anti-nitrotyrosine immunostaining and PARP was immunolocalized as a marker of apoptotic pathways.We found that NRF2 expression was increased in embryos from diabetic rats and decreased when the diabetic rats were treated with idebenone (p