Nutritional regulation of glutathione in stroke

Abstract

In contrast to cardiovascular disease, the impact of nutritional status on the prevention and outcome of stroke has received limited investigation. We present a mechanism based on animal studies, clinical data, and epidemiological data by which protein-energy status in the acute stroke and immediate postinjury periods may affect outcome by regulating reduced glutathione (GSH), a key component of antioxidant defense. As cysteine is the limiting amino acid for GSH synthesis, the GSH concentration of a number of nonneural tissues has been shown to be decreased by fasting, low-protein diets, or diets limiting in sulfur amino acids. The mechanism may also be relevant in brain since GSH in some brain regions is responsive to dietary sulfur amino acid supply and to the pro-cysteine drug, L-2-oxothiazolidine-4-carboxylate. The latter is an intracellular cysteine delivery system used to overcome the toxicity associated with cysteine supplementation. These findings may provide the mechanism to explain both the inverse correlation between dietary protein and stroke mortality and the documented association between suboptimal protein-energy status and diminished functional status following a stroke. Future investigations should examine the role of nutritional intervention in neuroprotective strategies aimed at improving stroke outcome. Pharmacological interventions such as L-2-oxothiazolidine-4-carboxylate should be investigated in animal models of stroke, as well as the impact of nutritional status on the response to these agents. Finally, micronutrient deficiencies that may accompany protein-energy malnutrition, such as selenium, should also be investigated for their role in antioxidant defense in cerebral ischemia.

Evidence of Blood and Muscle Redox Status Imbalance in Experimentally Induced Renal Insufficiency in a Rabbit Model

“…In patient studies, while general clinical guidelines are followed, dietary approaches can greatly influence GSH levels, contributing to literature's conflicting reports. GSH concentration is decreased by fasting, low-protein diets, or diets limiting in sulfur amino acids such as cysteine [54]. However, administration of α -lipoic acid, a naturally occurring thiol compound, increases GSH levels in several cell types and tissues [54–56] and also restores intracellular GSH in several pathological conditions [54].…”

“…GSH concentration is decreased by fasting, low-protein diets, or diets limiting in sulfur amino acids such as cysteine [54]. However, administration of α -lipoic acid, a naturally occurring thiol compound, increases GSH levels in several cell types and tissues [54–56] and also restores intracellular GSH in several pathological conditions [54]. Moreover, selenium (Se) as an integral part of the enzyme GPx plays a key role in GSH levels [57].…”

Protein-Energy Malnutrition Developing after Global Brain Ischemia Induces an Atypical Acute-Phase Response and Hinders Expression of GAP-43

“…With post-stroke feeding challenges, PEM prevalence rises to 20–35% after one week [2] , [4] and 35–49% by admission to a rehabilitation unit [5] , [6] . These unfortunate statistics were first documented more than two decades ago and span many countries [7] , [8] .…”

Protein–energy malnutrition increases activation of the transcription factor, nuclear factor κB, in the gerbil hippocampus following global ischemia☆

“…Approximately 16% of elderly patients present with protein-energy malnutrition (PEM) at the time of hospital admission for stroke (reviewed in Ref. [16]). Although most clinical studies addressing the impact of PEM on stroke outcome are limited by small sample size and study design, correlations have been drawn between PEM at stroke admission and increased risk of morbidity and mortality [17,18].…”