Redox state evaluation of hepatocytes treated with 5-aminolevunic acid

• Grant number: 10/51068-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: September 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Janice Onuki
• Grantee: Janice Onuki
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

5-Aminolevulinic acid (ALA) is the first precursor of heme, accumulated especially in the liver in some types of hepatic porphyrias, such as acute intermittent porphyria (AIP) and lead poisoning, due to a decrease in the porphobilinogen deaminase enzyme activity. Symptomatic patients of AIP present a higher incidence of hepatocellular carcinoma (HCC). In vitro, ALA produces reactive oxygen species (ROS) through the metal-catalyzed oxidation, triggering oxidative damage to DNA and proteins, which could be involved in the initiation and promotion of cancer. The final product of ALA oxidation, 4,5-dioxovaleric acid (DOVA) and the ALA condensation product, 6-dihydropyrazine-2,5-dipropanoic acid (DHPY) could also contribute to the deleterious potential of ALA. It has already been demonstrated that ALA is able do induce DNA damage such as single-strand breaks, increase in the level of 8-oxodGuo and 5-OHdCyd in organs of ALA-treated rats and increase in the formation of several modified DNA bases in vitro. ALA and DOVA also showed to be mutagenic in the Salmonella microssuspension mutagenicity assay and in SOS Chromotest. This project aims to evaluate several oxidative stress parameters and alteration in the gene and protein expressions related to apoptosis, cell cycle and DNA repair, promoted by ALA in primary hepatocytes. The investigation of ALA effecst in the cellular redox state and in the cell signaling pathways related to carcinogenesis is essential to understanding the molecular mechanisms involved in the correlation of ALA and its derivatives with the higher incidence of HCC im AIP patients, and also shed light into the ALA participation in tirosynosis, lead poisoning and photodynamic therapy. (AU)

Scientific publications

(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)

MENEZES, P. R.; GONZALEZ, C. B.; DESOUZA, A. O.; MARIA, D. A.; ONUKI, J.. Effect of 5-aminolevulinic acid on the expression of carcinogenesis-related proteins in cultured primary hepatocytes. MOLECULAR BIOLOGY REPORTS, v. 45, n. 6, p. 2801-2809, DEC 2018. (10/51068-6, 07/01966-5)

MENEZES, PATRICIA REGINA; TRUFEN, CARLOS EDUARDO MADUREIRA; LICHTENSTEIN, FLAVIO; PELLEGRINA, DIOGO VIEIRA DA SILVA; REIS, EDUARDO MORAES; ONUKI, JANICE. Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity. Archives of Biochemistry and Biophysics, v. 738, p. 10-pg., 2023-03-06. (10/51068-6, 07/01966-5)