STUDY OF HYPOXYA AND OXIDATIVE STRESS AT DIFFERENT LIFE PERIOD OF THE RATS AND THEIR OFFSPRING IN THE DIABETIC STATUS

• Grant number: 11/16241-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): January 01, 2012
• Effective date (End): December 31, 2014
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Débora Cristina Damasceno
• Grantee: Bruna Dallaqua
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 12/16084-6 - Study of hypoxya and oxidative stress markers at different life period of diabetic rats, BE.EP.DR

Abstract

Diabetes mellitus (DM) is a chronic disorder caused by the lack of insulin synthesis by pancreatic-beta cells or for defect in insulin receptors on target cells. There is evidence that hyperglycemia induces increased production of reactive oxygen species (ROS) due to increased intake of reducing the mitochondrial electron transport chain. To quantify the pro-oxidant agents exist biological markers thiobarbituric acid reactive species (TBARS), as malonaldehyde (MDA). The non-enzymatic endogenous and enzymatic antioxidants, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px, are responsible for defense mechanism against oxidative damage. The main source intracellular of ROS is the mitochondria and alterations associated to the mitochondrial phenotype in the diabetes have been widely described. To promote the mitochondrial biogenesis, studies show that peroxisome proliferator-activated receptor coactivator 1 alfa (PGC-1alfa) plays an important role. In addition, this protein is widely distributed in tissues and plays a key role in regulating cellular development and homeostasis of oxygen (O2). It has been shown that the mitochondrial biogenesis induced by PGC-1alpha increases O2 consumption, leading to decreased intracellular oxygen availability to HIF-hydroxylase enzymes, stabilizing the HIF-1alpha. The hypoxia-inducible factors (HIF) are among the transcription proteins more defined and identified as being regulated by intracellular redox state. HIF-1alpha is the main regulator of the O2 homeostase. In low concentrations of O2, there is activation of other factors to increase the liberation of O2 for the cells, facilitating the production of ATP, which is essential for embryonic development and earlier placentation. In order to understand more the main responsible mechanisms for alterations caused by diabetes, the use of laboratory animals is of great importance, because it offers essential tools for study the mechanisms involved in this syndrome. The literature shows that the induction of experimental diabetes with streptozotocin (STZ) before the 10th day of life of animal leads to partial destruction of beta cells, however, this regeneration occurs until the 10th day of life. With this, our research group aims to analyze hypoxia and oxidative stress markers in liver and blood of animals with mild diabetes, aiming to explain the mechanisms by which the hyperglycemia, post-excretion of STZ, leads to the hypoxia and oxidative stress along of the life. Moreover, it is of interest to investigate if the adverse intrauterine environment compromise the fetal programming, especially in relation to hypoxia and oxidative stress markers in these newborns, which would limit their growth and perinatal development.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DALLAQUA, Bruna. Influence of diabetes on oxidative stress status in different life moments of rats and their offpring. 2015. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.