Evaluation of reactive oxygen species on the epithelial and stromal prostate cell lines viability and prostate fragments of undergoing prostate resection patient reactivity.

• Grant number: 22/11621-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Pharmacology - Autonomic Pharmacology
• Principal Investigator: Fabíola Taufic Monica Iglesias
• Grantee: Gabriela Reolon Passos
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/15175-1 - Modulation of soluble guanylate cyclase and the intracellular levels of cyclic nucleotides in the lower urinary tract and prostate, AP.TEM
• Associated scholarship(s): 24/00216-8 - EVALUATION OF MULTIDRUG RESISTANCE PROTEINS TYPE 4 AND 5 IN CONTROLLING INTRACELLULAR LEVELS OF cAMP AND cGMP AND CELL PROLIFERATION IN PROSTATIC CELLS., BE.EP.PD

Abstract

Benign prostatic hyperplasia (BPH) is one of the most common prostatic disorders. Epidemiological studies indicate that BPH occurs in approximately 50% of men aged between 50-60 years, reaching about 90% in the ninth decade of life. Oxidative stress has been identified as one of the main causes of vascular complications associated with obesity. The reactive oxygen species (ROS) form under normal physiological conditions and is originated from molecular oxygen (O2) metabolism. Under physiological conditions, O2 is reduced, resulting in water formation. During this process, reactive intermediates are formed, such as superoxide anion (O2), hydrogen peroxide (H2O2) and hydroxyl (OH). Although oxidative pathways are important for many physiological processes, when there is an imbalance between the pro- and anti-oxidant systems, with a predominance of oxidants, oxidative stress occurs, contributing to several pathological states development, including BPH. In patients who had adenoma and prostate cancer, it was possible to observe a high level of ROS, especially H2O2 and the superoxide radical. The excessive production of ROS may be linked to exposure to androgens, which are directly linked to the development of prostate diseases, and are directly linked to occurrence, recurrence and progression. Recently, the interest in identifying sources that generate ROS and the development of pharmacological therapies targeting specific ROS generators has been gaining attention. Based on information above, our hypothesis is that ROS production is upregulated in response to BPH, probably with the specific contribution of different isoforms of NAPDH oxidase, NOX. Excessive generation of ROS, mainly superoxide, directly affects the intracellular signaling pathways essential to prostatic smooth muscle function, such as the NO-GCs-cGMP pathway, contributing to the previously observed hypercontractility state, in addition to pro-proliferative pathways in cells linages. Therefore, the aim of this study is evaluate the effect of ROS inhibition in epithelial (healthy and hyperplasic) and stromal myofibroblast cell lines and human smooth muscle prostate; and study the effect of ROS generation in epithelial (healthy and hyperplasic) and stromal myofibroblast cell lines and human smooth muscle prostate