Pyruvate preserves antiglycation defenses in porcine brain after cardiac arrest
An article published in Experimental Biology and Medicine (Volume 242, Issue 10, May, 2017) identifies a new treatment that may protect the brain from irreversible damage caused by cardiac arrest. The study, led by Dr. Robert Mallet, Professor of Cardiovascular and Metabolic Diseases at University of North Texas Health Science Center, showed that administration of pyruvate, an energy fuel and antioxidant, preserved brain function during cardiac arrest in a swine model.
The brain consumes enormous amounts of metabolic energy, and is utterly dependent on its blood supply to deliver energy-yielding fuels and oxygen. Consequently, interruptions in the brain’s blood supply can cause devastating effects. The depletion of energy stores and accumulation of toxic metabolites damages brain cells and can cause permanent impairment of brain function.
Methylglyoxal, a by-product of sugar metabolism, irreversibly damages proteins by a process termed glycation and accumulates in the brain when the oxygen supply is compromised. Glyoxalase, a special enzyme that decomposes methylglyoxal and prevents its accumulation, is also vulnerable to glycation. Thus, preventing the inactivation of glyoxalase could improve clinical outcomes for patients experiencing interruptions in the brain’s blood supply.
Pyruvate is a natural metabolite, and has been shown to protect the brain from injury. In this study, Dr. Mallet and coworkers investigated the impact of pyruvate on brain injury after cardiac arrest and cardiopulmonary resuscitation (CPR) in a swine model. They found that glyoxalase and other protective enzymes were inactivated in brains of anesthetized pigs following cardiac arrest and CPR. However, intravenous infusion of pyruvate preserved the activities of glyoxalase and other protective enzymes, and prevented methylglyoxal-induced protein glycation. According to Dr. Mallet, “cardiac arrest is devastating because it severely injures the brain. Moreover, those who are fortunate enough to survive cardiac arrest may be at increased risk of developing senile dementia. We are excited that pyruvate preserves the brain’s natural defenses against methylglyoxal when given in a timely fashion.”
Dr. Gary Scott, the lead author on the study, added that “this knowledge could foster development of treatments like pyruvate that augment the mechanisms protecting the brain from methylglyoxal and other toxic metabolites.”
Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, said, “Mallet and colleagues have demonstrated that pyruvate can block protein glycation upon cardiac arrest and cardio-cerebral resuscitation-induced ischemia-reperfusion. They further demonstrate that the mode of action of pyruvate is protection of the glyoxalase system. This opens the door to determining whether pyruvate can play a similar role in TBI and other neurological disorders.”