Abstract

Pyruvic acid, an intermediate metabolite of glucose, an effective scavengerof reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signalingpathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2),iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa,and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potentanti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its actionon glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndromeX, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhancedTNF-? production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassiumregimen in these clinical conditions, sepsis, and cancer.

Keywords: Cytokines - metabolism, Antioxidants - metabolism, Anti-Inflammatory Agents, Non-Steroidal - metabolism, Free Radicals - metabolism, Glucose - metabolism, Insulin - metabolism, Macrophage Migration-Inhibitory Factors - metabolism, Pyruvates - pharmacology, Pyruvic Acid - metabolism, Sepsis - metabolism, Tumor Necrosis Factor-alpha - metabolism