Anhydroecgonine methyl ester (AEME), a cocaine pyrolysis product, impairs glutathione-related enzymes response and increases lipid peroxidation in the hippocampal cell culture

Author(s)

Tamborelli Garcia, Raphael Caio ^{[1, 2]} ; Torres, Larissa Lobo ^{[1, 3]} ; Munhoz Dati, Livia Mendonca ^[1] ; de Melo Loureiro, Ana Paula ^[1] ; Afeche, Solange Castro ^[4] ; Lopes Sandoval, Maria Regina ^[4] ; Marcourakis, Tania ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Av Prof Lineu Prestes 580, Bl 13B, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, Dept Pharmaceut Sci, Rua Sao Nicolau 210, 1 Andar, BR-09913030 Diadema, SP - Brazil

^[3] Univ Fed Alfenas, Sch Pharmaceut Sci, Dept Food & Drugs, Rua Gabriel Monteiro Silva 700, BR-37130001 Alfenas, MG - Brazil

^[4] Butantan Inst, Lab Pharmacol, Av Vital Brasil 1500, BR-05503900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: TOXICOLOGY REPORTS; v. 6, p. 1223-1229, 2019.
• Web of Science Citations: 0

Abstract

Crack cocaine smokers inhale, alongside with cocaine, its pyrolysis product, anhydroecgonine methyl ester (AEME). We have previously described AEME neurotoxic effect and its additive effect when co-incubated with cocaine. Our aim was to evaluate, the effect of AEME, cocaine and AEME-cocaine combination on glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activities after 3 and 6 h of exposure, periods previous to neuronal death. Lipid peroxidation was evaluated through malonaldehyde (MDA) levels at 3, 6, 24 and 48 h of exposure. All treated groups reduced neuronal viability after 24 h of exposure. AEME and cocaine decreased GPx, GR and GST activities after 3 and 6 h, with an increase in MDA levels after 48 h. AEME-cocaine combination decreased the enzymes activities after 3 and 6 h, showing an additive effect in MDA levels after 48 h. These data show that the glutathione-related enzymes imbalance caused by AEME, cocaine or AEME-cocaine combination exposure preceded neuronal death and lipid peroxidation. Moreover, the additive effect on lipid peroxidation observed with AEME-cocaine exposure after 48 h, suggest a higher neurotoxic effect after crack cocaine use when compared to cocaine alone. (AU)

• FAPESP's process: 11/02734-6 - Neuronal death pathway induced by methylecgonidine, cocaine pyrolysis product, and its involvement in addiction
• Grantee: Tania Marcourakis
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/11149-0 - Caracterization of death pathway, induced by metilecgonidine, product by cocaine pirolise.
• Grantee: Lívia Mendonça Munhoz Dati
• Support Opportunities: Scholarships in Brazil - Master