Exposure to ketamine, ethanol and ketamine-ethanol combination: neurotoxicity evaluation in SH-SY5Y neural cells

• Grant number: 17/21834-8
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2018
• End date: April 30, 2020
• Field of knowledge: Health Sciences - Pharmacy - Toxicological Analysis
• Principal Investigator: Raphael Caio Tamborelli Garcia
• Grantee: Raphael Caio Tamborelli Garcia
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The illegal use of synthetic anesthetic ketamine in adolescents and young adults is high. Also, it is important to mention its therapeutic use by depressive patients who do not respond to the conventional antidepressants drugs, besides the illegal use by health professionals due to the easiest access to obtain this anesthetic. Moreover, it is noteworthy the ubiquity of alcohol and its high consumption in Brazil, especially during adolescence, being consumed along with other substances, such as new psychotropic drugs (e.g. ketamine), which can cause irreversible damage to the central nervous system due to dangerous combinations. Thus, the aim of this study is to investigate the mechanisms underlying cell death after the exposure to ketamine (KT), ethanol (EtOH) and the KT-EtOH combination using SH-SY5Y human neuroblastoma cell culture. Concentration-response curves for the substances will be performed using cell viability assays (XTT, LDH and annexin / propidium iodide - flow cytometry). Proteins involved in the intrinsic (caspase-9, Bax and Bcl-2) and extrinsic (caspase-8 / 10) apoptosis; caspase-3/-7; cleaved and non-cleaved PARP-1; apoptosis independent of the caspase activation (AIF and ENDOG) and the autophagic process (LC3-II) will be evaluated. Methods described in this project include western blot, flow cytometry and immunofluorescence. (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)

REIS ASSUNCAO, HENRIQUE CHARLANTI; COELHO CRUZ, YAN MILEN; BERTOLINO, JESSICA SILVA; TAMBORELLI GARCIA, RAPHAEL CAIO; FERNANDES, LILIAM. Protective effects of luteolin on the venous endothelium. Molecular and Cellular Biochemistry, v. 476, n. 4, JAN 2021. (17/22028-5, 17/21834-8)

DOS SANTOS, LAISA ALIANDRO; DOS SANTOS, GABRIELA SALLES; BORGES FERNANDES, GUSTAVO ARIEL; CORREA, MICHELLE FIDELIS; DE FARIA ALMEIDA, CAROLINA APARECIDA; FERNANDES, LILIAM; MARCOURAKIS, TANIA; FERNANDES, JOAO PAULO S.; TAMBORELLI GARCIA, RAPHAEL CAIO. Neurotoxicity Assessment of 1-[(2,3-Dihydro-1-Benzofuran-2-yl)Methyl]Piperazine (LINS01 Series) Derivatives and their Protective Effect on Cocaine-Induced Neurotoxicity Model in SH-SY5Y Cell Culture. NEUROTOXICITY RESEARCH, v. 40, n. 6, p. 11-pg., 2022-11-07. (17/21834-8, 16/23139-2)