Melatonin down-regulates steroidal hormones, thymocyte apoptosis and inflammatory cytokines in middle-aged T. cruzi infected rats

Author(s)

Brazao, Vania ^[1] ; Santello, Fabricia Helena ^[1] ; Colato, Rafaela Pravato ^[1] ; Duarte, Andressa ^[1] ; Goulart, Amanda ^[1] ; Sampaio, Pedro Alexandre ^[1] ; Nardini, Viviani ^[1] ; Sorgi, Carlos Arterio ^[1] ; Faccioli, Lucia Helena ^[1] ; do Prado Jr, Jose Clovis

Affiliation

^[1] Univ Sao Paulo, Coll Pharmaceut Sci Ribeirao Preto FCFRP, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1866, n. 11 NOV 1 2020.
• Web of Science Citations: 0

Abstract

Chagas disease, triggered by the flagellate protozoan Trypanosoma cruzi (T. cruzi) plays a potentially threat to historically non-endemic areas. Considerable evidence established that the immuno-endocrine balance could deeply influence the experimental T. cruzi progression inside the host's body. A high-resolution multiple reaction monitoring approach (MRMHR) was used to study the influence of melatonin on adrenal and plasma steroidal hormones profile of T. cruzi infected Wistar rats. Young (5 weeks) and middle-aged (18 months) male Wistar rats received melatonin (5 mg/Kg, orally) during the acute Chagas disease. Corticosterone, 11-dehydrocorticosterone (11-DHC), cortisol, cortisone, aldosterone, progesterone and melatonin concentration were evaluated. Interleukin-1 alpha and beta (IL-1 alpha and beta), IL-6 and transforming growth factor beta (TGF-beta) were also analyzed. Our results revealed an increased production of corticosterone, cortisone, cortisol and aldosterone in middleaged control animals, thus confirming the aging effects on the steroidal hormone profile. Serum melatonin levels were reduced with age and predominantly higher in young and middle-aged infected rats. Melatonin treatment reduced the corticosterone, 11-DHC, cortisol, cortisone, aldosterone and progesterone in response to T. cruzi infection. Decreased IL-1 alpha and beta concentrations were also found in melatonin treated middle-aged infected animals. Melatonin treated middle-aged control rats displayed reduced concentrations of TGF-beta. Melatonin levels were significantly higher in all middle-aged rats treated animals. Reduced percentages of early and late thymocyte apoptosis was found for young and middle-aged melatonin supplemented rats. Finally, our results show a link between the therapeutic and biological effects of melatonin controlling steroidal hormones pathways as well as inflammatory mediators. (AU)

• FAPESP's process: 15/09806-3 - Melatonin and senescence : study the modulation of the immune system during experimental infection with Trypanosoma cruzi.
• Grantee: José Clóvis do Prado Júnior
• Support Opportunities: Regular Research Grants