title: Inhibition of brain citrate synthase activity in an animal model of sepsis.
abstract: OBJECTIVE
  An extensive body of evidence from experimental studies indicates that sepsis is associated with increased reactive oxygen species production, depletion of antioxidants, and accumulation of markers of oxidative stress. Moreover, mitochondrial dysfunction has been implicated in the pathogenesis of multiple organ dysfunction syndrome (MODS). Citrate synthase is an enzyme localized in the mitochondrial matrix and an important component of the Krebs cycle; consequently, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase activity in the brains of rats submitted to a cecal ligation puncture model of sepsis.
  
  
  METHODS
  At several times points (3, 6, 12, 24 and 48 hours) after the cecal ligation puncture operation, six rats were killed by decapitation. Their brains were removed, and the hippocampus, striatum, cerebellum, cerebral cortex and prefrontal cortex were dissected and used to determine citrate synthase activity.
  
  
  RESULTS
  We found that citrate synthase activity in the prefrontal cortex was inhibited 12, 24 and 48 hours after cecal ligation puncture. In the cerebral cortex, citrate synthase activity was inhibited 3, 12, 24 and 48 hours after cecal ligation puncture. Citrate synthase was not affected in the hippocampus, striatum or cerebellum up to 48 hours after cecal ligation puncture.
  
  
  CONCLUSIONS
  Considering that energy impairment due to mitochondrial dysfunction in sepsis has been well described and that oxidative stress plays a crucial role in sepsis development, we believe that energy impairment may also be involved in these processes. If citrate synthase inhibition also occurs in a sepsis model, it is tempting to speculate that a reduction in brain metabolism may be related to the pathophysiology of this disease.
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Natália
authors.initials: N
authors.lastname: Rochi
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Joana
authors.initials: J
authors.lastname: Benedet
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Gabriela Kozuchovski
authors.initials: GK
authors.lastname: Ferreira
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Brena Pereira
authors.initials: BP
authors.lastname: Teodorak
authors.affiliation: Laboratório de Neurociências, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Clarissa Martinelli
authors.initials: CM
authors.lastname: Comim
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Larissa de Souza
authors.initials: Lde S
authors.lastname: Constantino
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Francieli
authors.initials: F
authors.lastname: Vuolo
authors.affiliation: Laboratório de Neurociências, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Leandra Celso
authors.initials: LC
authors.lastname: Constantino
authors.affiliation: Laboratório de Neurociências, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.affiliation: Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol