Inhibitory effect of local anesthetics on complex I inhibition-stimulated mitochondrial reactive oxygen species production

• Grant number: 12/18351-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2012
• End date: June 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Roger Frigério Castilho
• Grantee: Ivan Gallo Cappelli
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 11/50400-0 - Mitochondrial energy metabolism, redox state and functionality in cell death and cardiometabolic and neurodegenerative disorders, AP.TEM

Abstract

Parkinson´s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compact. Post-mortem studies showed a partial inhibition (20 - 40 %) of the mitochondrial respiratory chain complex I and oxidative damage in brain tissue from patients with idiopathic Parkinson´s disease. In the present study, the effect of local anesthetics will be evaluated on complex I inhibition-stimulated mitochondrial reactive oxygen species production. The experiments will be conducted with isolated rat brain mitochondria treated with rotenone, a classical respiratory complex I inhibitor. The effect of the local anesthetics dibucaine, procaine, lidocaine, and bupivacaine will be evaluated on mitochondrial oxygen consumption and reactive oxygen species production. The results may support the proposition of new interventions that are able to prevent, or at least reduce, the increased mitochondrial production of reactive oxygen species induced by partial inhibition of complex I of the respiratory chain.(AU)