Metabolomic investigation of cocaine toxicity on sleep deprived rats, using liquid chromatography attached to mass spectrometry

Author(s)

Lucas André Lobo Gomes

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2013-08-05

Examining board members

Marina Franco Maggi Tavares; Ernani Pinto Junior; Altay Alves Lino de Souza

• Advisor: Marina Franco Maggi Tavares

Abstract

In a society that deals daily with pressure to complete its tasks, sleep deprivation is a common consequence. As an excuse to keep oneself fit to work but to have fun at night some people use cocaine, whose consumption is studied for decades, but the association with sleep deprivation had not yet been evaluated by toxicology. This study uses metabolomics to generate a map of metabolic abnormalities associated with these conditions and its iteration. Using liquid chromatographic in HILIC mode and \"time of flight\" mass spectrometry (TOF), mass chromatograms of urine from 60 male Wistar rats were analysed using XCMS package (Bioconductor) running on R platform. Statistical data treatment (PCA, OPLS-DA, MANOVA) were performed using the programs SIMCA P + 11 and IBM SPSS, culminating in putative metabolites assignments that discriminate the conditions in the study (cocaine effect, total sleep deprivation effect and their combined effect). We highlighted five biological markers of damage associated with cocaine, three associated with sleep deprivation and their iteration. These metabolites were putatively identified by public databases (Metlin, MassTrix, HMDB, Lipidmaps) and their associated metabolic pathways were assessed through KEGG database. There are significant differences on metabolic pathways of the tyrosine cycle, the dopaminergic system and the citrate cycle. (AU)

• FAPESP's process: 11/13161-7 - METABOLOMIC INVESTIGATION OF COCAIN TOXICITY IN MICE, USING CAPILAR ELECTROFORESIS COUPLED TO MASS SPECTROMETRY.
• Grantee: Lucas André Lobo Gomes
• Support Opportunities: Scholarships in Brazil - Master