Cardiac oxidative stress is involved in heart failure induced by thiamine deprivation in rats

Abstract

Thiamine is an important cofactor of metabolic enzymes, and its deficiency leads to cardiovascular dysfunction. First, we characterized the metabolic status measuring resting oxygen consumption rate and lactate blood concentration after 35 days of thiamine deficiency (TD). The results pointed to a decrease in resting oxygen consumption and a twofold increase in blood lactate. Confocal microscopy showed that intracellular superoxide (approximately 40%) and H(2)O(2) (2.5 times) contents had been increased. In addition, biochemical activities and protein expression of SOD, glutathione peroxidase, and catalase were evaluated in hearts isolated from rats submitted to thiamine deprivation. No difference in SOD activity was detected, but protein levels were found to be increased. Catalase activity increased 2.1 times in TD hearts. The observed gain in activity was attended by an increased catalase protein level. However, a marked decrease in glutathione peroxidase activity (control 435.3 + or - 28.6 vs. TD 199.4 + or - 30.2 nmol NADPH x min(-1) x ml(-1)) was paralleled by a diminution in the protein levels. Compared with control hearts, we did observe a greater proportion of apoptotic myocytes by TdT-mediated dUTP nick end labeling (TUNEL) and caspase-3 reactivity techniques. These results indicate that during TD, reactive oxygen species (ROS) production may be enhanced as a consequence of the installed acidosis. The perturbation in the cardiac myocytes redox balance was responsible for the increase in apoptosis.

Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

“…It is well known that severe thiamine deficiency is often accompanied by acute congestive heart failure. A recent study showed that thiamine deficiency-induced heart failure in the rat involves oxidative stress induced apoptosis [97]. Furthermore, thiamine deficiency impairs contractile function in cardiomyocytes [98].…”

Thiamine Therapy for Heart Failure: a Promise or Fiction?

“…However, animal experiments have shown that thiamine depletion causes increased reactive oxygen species concentrations and increased cardiomyocyte apoptosis [16,17].…”

HDAC2 is required by the physiological concentration of glucocorticoid to inhibit inflammation in cardiac fibroblasts

“…In the way of reducing the activity and expression of HDAC2, oxidative stress may down-regulate the actions of GCs on inflammation, thereby contribute to the inflammatory response and GC resistance. Actually, that may be the cases for cardiovascular diseases and CHF, in which both of increased oxidative stress and chronic inflammation were increasingly recognized as important D r a f t 17 pathogenic mechanisms (Chen et al 2004;Gioda et al 2010;Grieve and Shah 2003;Xu et al 2011). Thus, the simply anti-inflammatory treatment with exogenous glucocorticoids for those patients with CHF always failed to delay the potential heart failure events in the clinic practice.…”