M. Fink
Dec 1, 2010
Citations
0
Influential Citations
7
Citations
Journal
The Journal of surgical research
Abstract
Pyruvate, the anionic form of a simple a-keto acid, plays a key role in intermediary metabolism, being the end-product of glycolysis and the starting substrate for the tricarboxylic acid (TCA) cycle. Additionally, pyruvate reacts rapidly and non-enzymatically with the reactive oxygen species (ROS), hydrogen peroxide (H2O2). Scavenging of H2O2 by endogenously generated pyruvate is probably a key cellular defense against oxidative stress, particularly in proliferating cells [1, 2]. As both a metabolic substrate and an effective ROS scavenger, pyruvate would seem to be an attractive candidate molecule for the treatment of conditions such as ischemia/reperfusion (I/R) injury or hemorrhagic shock, which are associated with impaired adenosine triphosphate production and/or oxidative stress. Indeed, administration of pyruvate to experimental animals has been shown to ameliorate organ damage and, in some instances, improve survival in various animal models of hemorrhagic shock [3–5] as well as myocardial [6, 7], intestinal [8, 9], hepatic [10], or central nervous system [11, 12] I/R injury. In an article recently published in the Journal of Surgical Research, this line of investigation has been extended by Petrat and coworkers, who report that intravenous administration of sodium pyruvate solution ameliorated gut mucosal damage and arterial hypotension in rats subjected to mesenteric I/R [13]. In the study by Petrat et al., treatment with sodium pyruvate was started before the induction of mesenteric ischemia, and treatment was continued through the first 60 min of the 120-min reperfusion period. The total dose of sodium pyruvate administered was 50, 250, or 1000 mg/kg. Only the middle dose of sodium pyruvate (250 mg/kg) significantly increased arterial blood pressure compared with untreated controls during the reperfusion phase. For other key read-outs, such as the extent of microscopic mucosal damage, the three doses of sodium pyruvate provided approximately equivalent degrees of protection, although for most of these other end-points, 250 mg/kg appeared to be the most effective dose. The findings reported by Petrat and colleagues are convincing, and represent a valuable contribution to the field. A few points, however, warrant comment. First, as noted already, the study employed a pretreatment design. Accordingly, the findings might not be applicable to a more clinically relevant scenario, wherein treatment is started only after mesenteric ischemia is already present. In this regard, it is noteworthy that in rodent models of transient cerebral ischemia, treatment with sodium pyruvate was shown to be effective when given before or shortly after the onset