Treatment with losartan of acute and delayed damages induced by ionizing radiation on testes: a potential strategy for oncofertility?

• Grant number: 19/09488-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2021
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Maria Angélica Spadella Santos
• Grantee: Maria Angélica Spadella Santos
• Host Institution: Faculdade de Medicina de Marília (FAMEMA). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). Marília , SP, Brazil
• Associated researchers: Agnaldo Bruno Chies ; Marco Aurélio Gouveia Alves

Abstract

Radiotherapy is a common treatment of cancer. However, exposure to ionizing radiation alters cellular morphology due to oxidative stress in both tumoral and healthy tissues. This therapy been increasingly used, especially to treat prostate cancer, one of the most common types of cancer among the men. Furthermore, there is a high number of children, adolescents and young adults being suggested to radiotherapy due to oncologic diagnosis and this exposure may severely affect their reproductive ability in the long-term. However, the mechanisms that mediate those radiation effects in testis remains unknown. Overall, to prevent or minimize cellular and tissue damage, the use of radioprotective agents can raise the radioresistence threshold of adjacent healthy tissues, thus allowing the use of higher doses of radiation against tumor. The action of drugs that inhibit renin-angiotensin-aldosterone system (RAAS) in the radioprotection of cellular damage was evidenced in lung, kidney and brain. In addition, the presence of intrinsic RAAS in the male reproductive system has already been verified, where it participates in physiological processes such as spermatogenesis. Then, the aim of the present study is to unveil the molecular mechanisms mobilized by the RAAS, which radiation affects male reproductive system. In addition, we aim to study the effects of losartan, an AT1 antagonist, on acute and delayed damages in irradiated testes, and how it can protect the reproductive health of males subjected to this exposure. (AU)