Abstract / Summary
Thiamine (vitamin B1) deficiency is known to cause predominantly neurological and cardiovascular symptoms due to the metabolic function of its diphosphate derivative as a coenzyme. A variety of natural and synthetic thiamine antimetabolites can simulate this deficiency. Oxythiamine may be spontaneously produced from thiamine itself and is known to accumulate in patients with kidney disorders. In this study, tissue specificity of chronic oxythiamine administration was investigated in male rats, focusing on changes in the physiology and thiamine-dependent enzyme activities of the cerebral cortex and heart. While oxythiamine treatment significantly reduced the pyruvate dehydrogenase activity in both tissues, its cerebral effects also included mild downregulation of another thiamine-dependent enzyme, 2-oxoglutarate dehydrogenase, indicating higher susceptibility of the cerebral metabolism to oxythiamine exposure. The oxythiamine neurological effects were also reflected in the rats’ altered anxiety-like behavior and heart rate regulation. Further investigation of the cerebral effects of oxythiamine identified elevated 3-hydroxybutyrate and protein acetylation as indicators of perturbed acetyl-CoA utilization in the TCA cycle. Some heart-specific changes, such as decreased glutathione level, were also observed upon oxythiamine treatment. The present results highlight the consequences of chronic oxythiamine exposure. These finding are potentially relevant for understanding the metabolic changes in the brain and heart upon pathophysiological oxythiamine accumulation.