Melatonin and senescence : study the modulation of the immune system during experimental infection with Trypanosoma cruzi.

• Grant number: 15/09806-3
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2015
• End date: January 31, 2019
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: José Clóvis do Prado Júnior
• Grantee: José Clóvis do Prado Júnior
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Despite all the scientific advances in recent decades in order to unravel the host's immune processes and the fparasite evasion, Chagas disease is still a major public health problem. Life expectancy in Brazil has increased every year and this growth allows the emergence of an elderly population at risk of contracting Chagas disease. The immune response as well as most of the physiological functions decline with age, being this fact a probable theoretical explanation of the aging process. An important factor that may be involved both in the progression of Chagas disease and along the immunosenescence is the production of Reactive Oxygen Species (ROS). It is known that high levels of ROS in the host's tissues contribute to oxidative stress causing tissue damage which reflect the severity of Chagas disease. Additionally, studies have shown that melatonin levels decrease along with the aging process contributing for the oxidative stress observed in these patients. Moreover, the beneficial effects of administration of this hormone have been reported. With this study, we will evaluate the cellular and molecular mechanisms involved in the changes of immunity throughout life expectancy and its consequences in chronic T. cruzi infected and aged hosts. The findings and the analysis of the involvement of apoptosis processes, oxidative stress and inflammation during Chagas disease will be of great importance in the development of future immune intervention strategies - therapy aimed enabling a more effective host's immune response during infection. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

COLATO, RAFAELA PRAVATO; BRAZAO, VANIA; DO VALE, GABRIEL TAVARES; SANTELLO, FABRICIA HELENA; SAMPAIO, PEDRO ALEXANDRE; TIRAPELLI, CARLOS RENATO; PEREIRA-DA-SILVA, GABRIELA; DO PRADO, JR., JOSE CLOVIS. Cytokine modulation, oxidative stress and thymic dysfunctions: Role of age-related changes in the experimental Trypanosoma cruzi infection Check for updates Age-related thymic dysfunctions and Trypanosoma cruzi infection. CYTOKINE, v. 111, p. 88-96, NOV 2018. (14/00303-6, 15/09806-3)

BRAZAO, VANIA; SANTELLO, FABRICIA HELENA; COLATO, RAFAELA PRAVATO; DUARTE, ANDRESSA; GOULART, AMANDA; SAMPAIO, PEDRO ALEXANDRE; NARDINI, VIVIANI; SORGI, CARLOS ARTERIO; FACCIOLI, LUCIA HELENA; DO PRADO JR, JOSE CLOVIS. Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1866, n. 11, NOV 1 2020. (15/09806-3)

BRAZAO, VANIA; SANTELLO, FABRICIA HELENA; COLATO, RAFAELA PRAVATO; PRADO, JOSE CLOVIS. T. cruzi infection among aged rats: Melatonin as a promising therapeutic molecule. Experimental Gerontology, v. 135, JUL 1 2020. (11/20673-4, 10/02222-2, 15/09806-3)

BRAZAO, VANIA; COLATO, RAFAELA PRAVATO; SANTELLO, FABRICIA HELENA; DUARTE, ANDRESSA; GOULART, AMANDA; SAMPAIO, PEDRO ALEXANDRE; SILVA, CARLA B. PACHECO; TIRAPELLI, CARLOS RENATO; COSTA, RAFAEL M.; TOSTES, RITA C.; et al. Melatonin regulates antioxidant defense and inflammatory response by activating Nrf2-dependent mechanisms and inhibiting NFkappaB expression in middle-aged T. cruzi infected rats. Experimental Gerontology, v. 167, p. 9-pg., 2022-07-26. (15/09806-3)

BRAZAO, VANIA; COLATO, RAFAELA PRAVATO; SANTELLO, FABRICIA HELENA; DO VALE, GABRIEL TAVARES; GONZAGA, NATALIA DE ALMEIDA; TIRAPELLI, CARLOS RENATO; DO PRADO, JR., JOSE CLOVIS. Effects of melatonin on thymic and oxidative stress dysfunctions during Trypanosoma cruzi infection. Journal of Pineal Research, v. 65, n. 3, OCT 2018. (15/09806-3)