In obese placentas, a non-significant trend towards decreased TBARS levels as a lipid peroxidation biomarker was found (~25%, 0.05 relative to the lean group. decrease in C=O and TBARS levels in obese pregnancies. Although total SOD and catalase concentrations were shown to be increased, both activities were significantly downregulated in obese pregnancies, along with total antioxidant capacity. Inducible nitric oxide sintase levels were increased in the obese group compared to the lean group, accompanied by an increase in nitrotyrosine residues levels and lower levels of nitrosothiol groups in proteins such as ERK1/2. These findings reveal a reduction in oxidative damage, accompanied by a decline in antioxidant response, and an increase via NO-mediated nitrative stress in placental tissue from metabolically healthy pregnancies with obesity. All this plausibly points to a placental adaptation of the affected antioxidant response towards a NO-induced option pathway, through changes in the ROS/RNS balance, in order to reduce oxidative damage and preserve placental function in pregnancy. is an important source of production of pro-oxidant brokers in normal pregnancy, mainly due to the presence of a high mitochondrial metabolic activity and the action of enzymes such as NADPH oxidase or xanthine oxidase, responsible for the production of reactive oxygen species (ROS) such as superoxide anion (O2?) or hydrogen peroxide (H2O2). Under normal physiological conditions, these reactive species play important functions as second messengers in the cell signaling regulation. In pregnancy, these pathways can respond to a variety of stimuli or insult related to perturbations in the maternal blood supply to the placenta and inflammation. On the other hand, the placenta has a Targapremir-210 complex system of antioxidant response, including superoxide dismutase (SOD) or catalase (CAT) enzymes, which usually maintains the action of ROS in balance [15,16]. When the production of ROS exceeds the endogenous antioxidant defenses, a process known as oxidative stress (OS) occurs. OS is now recognized to play an essential role in certain placental-related disorders in pregnancy such as GDM, PE, and intrauterine growth retardation [17,18,19,20]. Nevertheless, the impact of an obesogenic milieu on placental redox status is still not completely understood. In this line, the maternal obesity associated with metabolic alterations seems to lead to the appearance of an elevated placental OS compromising both placental metabolism and antioxidant status. In contrast, no clear evidence has been found of increased OS in human placenta associated with increasing maternal body mass index (BMI), especially in overweight pregnant women [21,22]. Interestingly, pregravid maternal obesity contributes to the development of placental oxidative stress already in the first trimester of pregnancy [23]. In addition to ROS, the placenta can also generate reactive nitrogen species (RNS) in response to Targapremir-210 different inflammatory and metabolic mediators. Among them, nitric oxide (NO) is usually a pleiotropic signaling agent able to regulate key biological processes at the cellular level. An overproduction of Targapremir-210 Rabbit Polyclonal to STRAD NO by the nitric oxide synthase (NOS) enzyme has been widely implicated in the pathogenesis of different disorders, including cancer, diabetes, autoimmune, and cardiovascular diseases, along with pregnancy-related pathologies [24]. In these events, NO disrupts protein signaling pathways by mechanisms termed post-translational modifications (PTMs), including protein S-Nitrosylation and Nitration, which may affect its biological functions by forming NO-derived complexes known as S-nitrosothiol (?SNO) and nitrotyrosine (?NO2), respectively. Our group has recently pointed out S-Nitrosylation as a crucial mechanism through which NO specifically regulates certain key placental proteins in pregnancies with GDM [25]. This phenomenon has also been proposed to play a role in the placental pathophysiology in PE, both leading to nitrosative stress [26]. Moreover, the combination of NO and O2? produces peroxynitrites (ONOO?), a powerful pro-oxidant that can exert different deleterious effects by protein nitration, forming nitrotyrosine residues [27]. In this line, many relevants cellular proteins are potential ONOO? targets, including transporters, enzymes, structural proteins, and signal transduction.
In obese placentas, a non-significant trend towards decreased TBARS levels as a lipid peroxidation biomarker was found (~25%, 0
