title: Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine inhibit cytochrome C oxidase in mouse brain regions.
abstract: The highly active antiretroviral therapy completely changed the clinical evolution of HIV infection, reducing the morbidity and mortality among human immunodeficiency virus (HIV)-1 infected patients. Therefore, in the present study we evaluated the effect of chronic efavirenz (EFV) and nevirapine (NVP) administration on mitochondrial respiratory chain complexes activities (I, II, II-III, IV) in different brain regions of mice. Mice were orally administered via gavage with EFV 10 mg/kg, NVP 3.3 mg/kg or vehicle (controls) once a day for 36 days. We observed that the complex IV activity was inhibited by both EFV and NVP in cerebral cortex, striatum and hippocampus of mice, but not in cerebellum, as compared to control group. In contrast, chronic EFV and NVP administration did not alter complexes I, II and II-III. We speculated that brain energy metabolism dysfunction could be involved in the CNS-related adverse effects.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av Universitária, 1105 Bairro Universitário, Criciúma, SC 88806-000, Brazil. emiliostreck@gmail.com
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
authors.forename: Gabriela K
authors.initials: GK
authors.lastname: Ferreira
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.forename: Gislaine T
authors.initials: GT
authors.lastname: Rezin
authors.forename: Cinara L
authors.initials: CL
authors.lastname: Gonçalves
authors.forename: Isabela C
authors.initials: IC
authors.lastname: Jeremias
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Zugno
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Ferreira
authors.forename: Jeverson
authors.initials: J
authors.lastname: Moreira
authors.forename: Celine M
authors.initials: CM
authors.lastname: Fochesato
authors.forename: Pedro R T
authors.initials: PR
authors.lastname: Romão
mesh_terms: D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D003521:Cyclopropanes; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D019829:Nevirapine / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D003576:Electron Transport Complex IV; C098320:efavirenz