Inflammation and cancer: evaluation of Ccl2 and TGF-beta pathways in prostatic carcinogenesis in old rats submitted to maternal protein restriction and sugar consumption until adult life.

Author(s)

Matheus Naia Fioretto

• Document type: Master's Dissertation
• Press: Botucatu. 2021-04-28.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2021-02-24
• Advisor: Luis Antonio Justulin

Abstract

Epidemiological and experimental studies have been demonstrated higher rate of obesity, diabetes and cardiovascular diseases in the adult population of individuals whose mothers had inadequate conditions during pregnancy, such as maternal low protein diet (LPD). Recently, experimental studies have demonstrated that the reproductive system are also affected by maternal LPD in the offspring rats. Linked to this, the increasing consumption of "added sugar" in the world has been associated to the global increase of metabolic diseases cases. Thus, maternal LPD and sugar consumption may be associated with inflammatory processes in the prostate with aging. Therefore, this project aims to investigate the role of inflammation pathways in rats submitted to maternal LPD, which together were exposed to sugar consumption, focusing on the ventral prostate (VP). Male Sprague Dawley offspring rats submitted or not to maternal LPD was used (CEUA951). Rats born from dams fed with control diet (CTR, 17% protein) or low protein diet (GLLP, 6% protein) during gestation and lactation period were divided in 4 experimental groups: Control (CTR) consumed control diet and water until PND 90; Control+sugar (CTR+SUG) consumed control diet and sugar solution (10% diluted in water) until PND 90; Gestational and Lactational Low Protein (GLLP) received normal water until PND 90; and GLLP+SUG consumed sugar solution until PND 90. On PDN 540 they were anesthetized, weighed, and euthanized. The collected blood was used for systemic analysis and the VP for morphological and molecular analysis. The results demonstrate a reduction in body weight in the GLLP and GLLP+SUG, an increase in the prostate relative weight, in addition to a lower amount of total fat. Metabolic parameters such as glucose, triglycerides and total proteins did not show significant differences, as well as oxidative stress parameters, which demonstrates that adverse conditions were not sufficient to trigger processes such as obesity, diabetes, and metabolic syndrome. Tissue changes in VP were observed in all experimental groups, with an emphasis on inflammatory infiltrate and inflammation for the GLLP and GLLP+SUG groups. Regarding inflammatory parameters, there was an increase in mast cells and CD68 macrophages in the VP of all groups when compared to CTR, in addition to the incidence of carcinoma in some animals in these groups. We observed a systemic and intra-prostate high expression of IL-6 molecules in the GLLP and an increase in TGF-b1 in the animals of the GLLP +SUG group. Associated with this, the phosphorylated SMAD2 3 was reduced, which can demonstrate that this inflammation pathway is exacerbated in the group that was submitted to both adverse conditions. With these results, it is possible to observe an influence of inflammation in the harmful processes related to aging, both in animals submitted to maternal LPD, and in the consumption of sugar, but with greater emphasis on those that presented both adverse conditions. This demonstrates that maternal LPD and sugar consumption negatively and directly affect prostatic homeostasis in senility, with the influence of inflammatory parameters, which may be related to the biology of cancer in this tissue. (AU)

• FAPESP's process: 19/10410-8 - Inflammation and cancer: evaluation of CCL2 and TGF-beta pathways in prostatic carcinogenesis in old rats submitted to maternal protein restriction and sugar consumption until adult life
• Grantee: Matheus Naia Fioretto
• Support Opportunities: Scholarships in Brazil - Master