Oxidative stress, thiamine deficiency

Oxidative stress contributes to selective neuronal cell death in thiamine-deficiency 600... 

Moreover, targeted disruption (knock-down) of the eNOS gene attenuates the neuronal cell death in thiamine-deficient mice (Gibson and Zhang, 2002). eNOS knock-down but not knock-down of iNOS or nNOS leads to a reduction in protein tyrosine nitration (Beauchesne et al., 2009), suggesting a major role of eNOS as the source of nitric oxide-related nitrosative stress in thiamine deficiency. 

Jolitha AB, Subramanyam MV, Asha Devi S (2006) Modification by vitamin E and exercise of oxidative stress in regions of aging rat brain studies on superoxide dismutase isoenzymes and protein oxidation status. Exp Gerontol 41(8) 753-763 Kruse M, Navarro D, Desjardins P, Butterworth RF (2004) Increased brain endothelial nitric oxide synthase expression in thiamine deficiency relationship to selective vulnerability. Neurochem Int45(l) 49-56... 

Shangari N et al., Toxicity of glyoxals-role of oxidative stress, metabolic detoxification and thiamine deficiency, Biochem. Soc. Trans., 31, 1390, 2003. 

Cafingasan, N. Y., et al., 1999. Oxidative stress is associated with region-specific neuronal death during thiamine deficiency. J Neuropathol Exp Neurol. 58, 946—958. 

Thiamine deficiency results in mitochondrial dysfunction in which compromised brain energy metabolism produces oxidative stress, exci-totoxicity and inflammatory responses leading to neuronal cell death. 

Persistent net ROS formation in thiamine deficiency can also initiate a cascade of cell death pathways via intracellular messengers, e.g. intracellular cas-pase-3-mediated apoptosis. Development of oxidative stress also leads to other disturbances in brain function, including an inhibition of glutamate uptake due to transporter protein nitrosylation following peroxynitrite formation (Hazell et al. 2003 Trotti et al. 1996 Volterra et al. 1994). Under conditions of oxidative stress, levels of HO-1, cNOS, iNOS, ICAM-1 and microglial activation are increased. Thus, oxidative stress can lead to profound neuropathological consequences in thiamine deficiency and WE. 

Oxidative stress is an important part of the pathophysiology of thiamine deficiency in which key proteins involved in processes such as nitric oxide production, apoptosis, and glutamate transport are affected. 

Oxidative stress and inflammation are two major consequences of thiamine deficiency. 

Hazell, A.S., and Butterworth, R.F., 2009. Update of cell damage mechanisms in thiamine deficiency focus on oxidative stress, excitotoxicity and inflammation. Alcohol and Alcoholism. 44 141-147. 

---