Evaluation of protein expression and biochemical parameters related to diabetes mellitus type II and dyslipidemias in animals exposed to the contaminants bisphenol A and S

• Grant number: 16/10456-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2016
• End date: March 29, 2020
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Fernando Barbosa Júnior
• Grantee: Lara Ferreira Azevedo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/19554-0 - Assessment of mechanisms associated with energy homeostasis disruption after bisphenol A or S exposures through untargeted metabolomics, BE.EP.DD

Abstract

Recent studies address the adverse effects caused by the emerging contaminant bisphenol A, compound commonly used to manufacture a variety of products and classified as an endocrine disruptor, once it has proven estrogenic activity in vitro and in vivo. Regarding the increasing concern about exposure to bisphenol A, many countries have begun to prohibit its use in consumer products and its analogue, bisphenol S, has been proposed as an alternative to replace the original one. However not much is known about this substance and some studies demonstrate that its toxicity is similar to bisphenol A. Currently, studies demonstrate that the exposure to bisphenols A and S can be correlated with the development of metabolic disorders, such as diabetes mellitus type II and dyslipidemias, yet the cellular and molecular mechanisms by which these compounds would be triggering such disorders are not well established, what demonstrates the need of new studies to elucidate these mechanisms. In this way, the present project aims to evaluate changes in protein expression in rats chronically exposed to bisphenols A and S. For this purpose, the animals will be divided into 7 groups (n=6) which will receive, via drinking water, weekly determined concentrations of both compounds, taking into account the average daily water intake and an average weight of animals, in order to expose them throughout the experiment to approximately 50 ¼g/kg/day (concentration 1) and 500 ¼g/kg/day (concentration 2) of bisphenols. The animals will be distributed as follows: (I) control - water containing 0.1% ethanol; (II) bisphenol A concentration 1; (III) bisphenol S concentration 1; (IV) both compounds (bisphenol A and S) concentration 1; (V) bisphenol A concentration 2; (VI) bisphenol S concentration 2; (VII) both compounds concentration 2. The assessment of protein alterations will be performed by proteomic analysis of liver and pancreas of all groups exposed to bisphenols. Besides that, it will be determinated biochemical parameters such as, plasmatic levels of triglicerides, cholesterol, LDL cholesterol, HDL cholesterol, glicose, alanine transaminase and aspartate transaminase shortly after the exposure period. At last, it will be conducted glucose tolerance test and insulin tolerance test in all the treated groups in the end of the exposure period. (AU)

Scientific publications

(4)

(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)

AZEVEDO, LARA FERREIRA; HORNOS CARNEIRO, MARIA FERNANDA; ROBERTO PORTO DECHANDT, CARLOS; CASSOLI, JULIANA SILVA; ALBERICI, LUCIANE CARLA; BARBOSA JR, FERNANDO. Global liver proteomic analysis of Wistar rats chronically exposed to low-levels of bisphenol A and S. Environmental Research, v. 182, MAR 2020. (18/24069-3, 16/10456-0)

AZEVEDO, LARA FERREIRA; PORTO DECHANDT, CARLOS ROBERTO; DE SOUZA ROCHA, CECILIA CRISTINA; HORNOS CARNEIRO, MARIA FERNANDA; ALBERICI, LUCIANE CARLA; BARBOSA JR, FERNANDO. Long-term exposure to bisphenol A or S promotes glucose intolerance and changes hepatic mitochondrial metabolism in male Wistar rats. Food and Chemical Toxicology, v. 132, OCT 2019. (18/24069-3, 16/23509-4, 16/10456-0)

AZEVEDO, L. FERREIRA; MASIERO, M. MIGUEL; CHERKAOUI, S.; CARNEIRO, M. F. HORNOS; JR, F. BARBOSA; ZAMBONI, N.. The alternative analog plasticizer BPS displays similar phenotypic and metabolomic responses to BPA in HepG2 and INS-1E cells. Food and Chemical Toxicology, v. 167, p. 14-pg., 2022-07-12. (18/24069-3, 16/10456-0, 18/19554-0)

AZEVEDO, LARA FERREIRA; KARPOVA, NINA; ROCHA, BRUNO ALVES; BARBOSA JR, FERNANDO; GOBE, GLENDA CAROLYN; CARNEIRO, MARIA FERNANDA HORNOS. Evidence on Neurotoxicity after Intrauterine and Childhood Exposure to Organomercurials. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 20, n. 2, p. 19-pg., 2023-01-01. (16/10456-0, 18/24069-3, 18/19554-0, 16/07661-0, 14/06744-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

AZEVEDO, Lara Ferreira. Use of omic approaches (proteomics and metabolomics) to elucidate bisphenols A and S mechanisms of toxicity in in vivo and in vitro models. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.