Maternal treatments with a mitochondrial antioxidant prevents maternal diabetes-induced programming of heart alterations

SABRINA LORENA ROBERTI; MARÍA BELÉN MAZZUCCO; ALICIA JAWERBAUM; ROMINA HIGA

Congreso; lnternational Association of the Diabetes and Pregnancy Study Groups (IADPSG); 2016

Maternal diabetes induces a pro-inflammatory and pro-oxidant environment and can program metabolic and cardiovascular diseases in the offspring. Idebenone is a coenzymeQ analogue, acting as a transporter in the mitochondrial electron transport chain and as an antioxidant. Mitochondrial biogenesis and function are regulated by peroxisome proliferator-activated receptor coactivator 1 alpha (PGC-1 alpha). Aims: To analyze the effect of idebenone administration during pregnancy on pro-inflammatory and pro-oxidant markers and on PGC-1alpha protein expression in the hearts of offspring from control and diabetic rats. Methods: Diabetes was induced by neonatal streptozotocin administration (90 mg/kg), leading to adult diabetic animals with fasting glycemia values between 130 and 230 mg/dl. Control and diabetic adult females were mated with control males. During pregnancy, rats were treated with idebenone (100 mg/kg, oral treatment) or vehicle (water). The heart was explanted in 21-day-old offspring for further evaluation of the levels of nitrotyrosine (a marker of peroxynitrite-induced damage), MMP9 (matrix metalloproteinase-9), CTGF (connective tissue growth factor, a pro-inflammatory and pro-fibrotic marker) and PGC-1alpha by immunohistochemisty. Results: We found increased protein nitration (p