Premium
Pyruvate‐Enhanced Cardiocerebral Resuscitation Via Nrf2/ARE Pathway
Author(s) -
Scott Gary
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.673.6
Subject(s) - glutamate receptor , excitotoxicity , chemistry , pyruvic acid , ischemia , medicine , endocrinology , biochemistry , receptor
Background Cardiac arrest‐cardiocerebral resuscitation (CA‐CCR) inflicts ischemia‐reperfusion (I/R) brain injury and glutamate excitotoxicity‐related cognitive deficits. Plasma pyruvate lowers blood glutamate to enhance brain glutamate efflux and neurocognition. Purpose: To test pyruvate reduction of plasma glutamate via Nrf2/antioxidant response element (ARE) regulated pathways. Methods: Swine subjected to CA received iv pyruvate or NaCl infusion to 4 mM during CCR. Carotid artery and frontal cortex lysates were assessed for Nrf2/ARE binding activity and glyoxalase1 (GLO1) activity, and pre‐ and post‐CA glutamate concentrations were measured in plasma. Results: In carotid artery and cortical lysates, Nrf2/ARE activity and Nrf2‐regulated GLO1 reductions were rescued by pyruvate. Plasma glutamate increased after CA‐CCR, but was sharply reduced by pyruvate. Conclusions Nrf2/ARE binding and GLO1 activity in cortex and carotid arteries were suppressed after CA‐CCR but partly restored by pyruvate. Similarly, post‐CA plasma glutamate surges were reversed by pyruvate in a manner supporting Nrf2‐regulated mechanisms of brain glutamate clearance, reduced excitotoxicity and brain protection.