title: Cocaine-induced status epilepticus and death generate oxidative stress in prefrontal cortex and striatum of mice.
abstract: Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) with cocaine 90 mg/kg and observed during 1h. After this cocaine overdose some animals presented status epilepticus (SE) while some died after seizures. These animals were divided in two groups, SE and death. A group with an association of the antioxidant Vitamin E (Vit E, 400mg/kg, i.p.) plus Coc 90 (Vit E plus Coc 90) was undertaken to assess the neuroprotective effect of Vit E. Neurochemical analyses were carried out in prefrontal cortex (PFC) and striatum (ST). GSH levels increased only after cocaine-induced death in both areas studied. Cocaine-induced SE has increased nitrite/nitrate content in PFC and ST, while after death the increase was only in PFC. MDA (the lipid peroxidation marker) was elevated after SE and death in ST and only after death in PFC. Antioxidant treatment significantly reduced the GSH, nitrite/nitrate in ST and MDA levels. Only nitrite/nitrate content in PFC has not been decreased by Vit E pretreatment. The results relate that oxidative stress occurs after cocaine-induced toxicity mainly after death indicating that probably the increase of OS in the animal's brain leads to seizures and death, also showing a protective effect of Vit E in this process. Together with previous results this study contributes to the knowledge of cocaine-induced toxicity and possible in the near future to the use of antioxidants in the prevention of cocaine-induced CNS toxicity.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. daniellesm2000@yahoo.com
authors.forename: Danielle Silveira
authors.initials: DS
authors.lastname: Macêdo
authors.forename: Silvânia Maria Mendes
authors.initials: SM
authors.lastname: Vasconcelos
authors.forename: Manoel
authors.initials: M
authors.lastname: Andrade-Neto
authors.forename: Luciana Dias
authors.initials: LD
authors.lastname: Belchior
authors.forename: José Eduardo Ribeiro
authors.initials: JE
authors.lastname: Honório Júnior
authors.forename: Danilo Oliveira
authors.initials: DO
authors.lastname: Gonçalves
authors.forename: Marta Maria França
authors.initials: MM
authors.lastname: Fonteles
authors.forename: Maria Izabel Gomes
authors.initials: MI
authors.lastname: Silva
authors.forename: Lissiana Magna Vasconcelos
authors.initials: LM
authors.lastname: Aguiar
authors.forename: Glauce Socorro Barros
authors.initials: GS
authors.lastname: Viana
authors.forename: Francisca Cléa Florenço
authors.initials: FC
authors.lastname: de Sousa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D003042:Cocaine / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003645:Death, Sudden / Q000209:etiology*; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013226:Status Epilepticus / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D024505:Tocopherols / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D018765:Dopamine Uptake Inhibitors; D009566:Nitrates; D009573:Nitrites; D008315:Malondialdehyde; D005978:Glutathione; D003042:Cocaine; D024505:Tocopherols