Characterization of mechanisms of action of in vivo hydroquinone exposure on lung mast cells and macrophages

• Grant number: 09/03964-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2009
• End date: March 31, 2011
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Sandra Helena Poliselli Farsky
• Grantee: Ana Lucia Borges Shimada
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The aim of this project is investigate the lung inflammatory reaction in Male Swiss mice exposed to hydroquinone (HQ), a phenolic agent obtained from benzene biotransformation, and an important compound of cigarette, medicines and foods. It will be employed concentrations equivalent to those allowed by Legislative Agencies, 0,75mg/60mL/1h (12,5ppm); 1,5mg/60mL/1h (25ppm) or 3mg/60mL/1h (50 pppm), once a day, during 5 days, by inhalatory pathway, as it is the main via of exposure. Control animals will receive the same amount of vehicle. Three hours after the induction of inflammatory reaction (LPS of E. coli; 0.1 mg/mL; 10 min inhalatory pathway), the bronchoalveolar fluid will be collected to quantify the concentrations of cytokines (IL-1beta, IL-6, MCP-1, RANTES, MIP3alpha, TNF-alpha, IFN-gamma, by ELISA) eicosanoids (PGE2 and LTB4, by ELISA) and nitric oxide (by Greiss reaction). Additionally, resident cells from respiratory tract (mast cell and macrophages) will be collected from exposed animals to investigate their functions. Macrophages will be collected from bronchoalveolar fluid and mast cells from distal region of trachea. The ability of these cells to secrete TNF-alpha and LTB4 will be evaluated after in vitro LPS stimulation. The ability of macrophages to phagocyte and kill Candida albicans will be investigated by optical microscopy. Data here obtained may contribute to clarify the toxic mechanism of action of HQ and to provide end points more sensitive to intoxications.

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)

BORGES SHIMADA, ANA LUCIA; TEROSO RIBEIRO, ANDRE LUIZ; BOLONHEIS, SIMONE MARQUES; FERRAZ-DE-PAULA, VIVIANE; HEBEDA, CRISTINA BICHELS; POLISELLI FARSKY, SANDRA HELENA. In vivo hydroquinone exposure impairs MCP-1 secretion and monocyte recruitment into the inflamed lung. Toxicology, v. 296, n. 1-3, p. 20-26, JUN 14 2012. (09/03964-5)

BORGES SHIMADA, ANA LUCIA; LINO-DOS-SANTOS-FRANCO, ADRIANA; BOLONHEIS, SIMONE MARQUES; NAKASATO, ANDRE; DAMAZO, AMILCAR SABINO; TAVARES-DE-LIMA, WOTHAN; POLISELLI FARSKY, SANDRA HELENA. In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells. Toxicology Letters, v. 211, n. 1, p. 10-17, 2012. (09/03964-5)

Academic Publications

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

SHIMADA, Ana Lucia Borges. Effects of in vivo hydroquinone exposure on functions of alveolar macrophages and tracheal tissue in mice. 2011. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.