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Correlation between dietary intake of Aflatoxin B1, hepatic expression of the genes and proteins related to hepatocarcinogenesis, and concentration of AFB1-adducts in serum, urine and liver of wistar rats

Grant number: 13/04627-8
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2013
Effective date (End): October 19, 2014
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Fernando Silva Ramalho
Grantee:Mauricio de Rosa Trotta
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:10/20895-4 - Evaluation of AFB1-Lisin and AFB1-N7-guanin aducts as biomarkers of human and animal exposure to aflatoxins, AP.TEM


Aflatoxins are mycotoxins produced by fungi of the genus Aspergillus, which in Brazil have ideal conditions for its growth, mainly as a contaminant of grains and cereals. These substances, especially aflatoxin B1 (AFB1), possess remarkable power toxigenic. AFB1 is highly mutagenic and potent liver carcinogen in different species, including humans. After oral ingestion of AFB1, its biotransformation occurs in the liver and yield of metabolites (adducts) that can be present in different tissues and body fluids. However, no correlations has been established between intake of various concentrations of AFB 1 in the diet and its metabolites in the liver, serum and urine as well as the intensity of hepatic expression of genes and proteins related to hepatocarcinogenesis. Male Wistar rats will receive AFB1 at different doses by oral route, constituting four experimental groups. An additional group will reveive receive, besides the AFB1, diet containing 5% ethanol. Control animals will not expose to mycotoxin or ethanol. After chronic exposure for 90 days, the animals will be euthanized for collection of serum and hepatic parenchyma. Urine will be collect during the last week of exposure to the toxin. It will make eterminations of the levels of adducts of AFB1 in serum, urine and liver, and changes in hepatic expression of genes and proteins related to the process of hepatocarcinogenesis (p53, p21WAF1/CIP1, p27KIP1, Rb, p16INK4D, b-catenin, cyclin D1, prohibitin and glutathione-S-transferase-p1) using immunohistochemical, western-blotting and real-time PCR techniques. Histopathological changes in liver and serum biochemistry will also be assessed.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
TROTTA, Mauricio de Rosa. Correlation between aflatoxin B1 intake and serum and urinary concentrations of AFB1-adducts and hepatic expression of molecular markers related to hepatocarcinogenesis in rats. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto Ribeirão Preto.

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