Impact of glutathione on acute ischemic stroke severity and outcome: possible role of aminothiols redox status

Abstract

Objective: Acute brain ischemia is accompanied by a disruption of low-molecular-weight aminothiols (LMWTs) homeostasis, such as homocysteine (Hcy), cysteine (Cys), and glutathione (GSH). We investigated the redox balance of LMWTs in blood plasma and its influence on ischemic stroke severity and the functional outcome in patients with an acute period. Patients and methods: A total of 177 patients were examined. Total and reduced forms of LMWTs were determined in the first 10-24 h. Stroke severity and functional state were estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRs) at admission and after 21 days. Results: Patients with high levels of total Hcy (> 19 μM) showed significantly reduced redox statuses of all LMWTs. Patients with low total GSH levels (≤ 1.07 μM) were at an increased risk of higher stroke severity (NIHSS > 10) compared to patients with a total GSH level > 2.64 μM (age/gender-adjusted odds ratio: 4.69, 95% CI: 1.43-15.4). Discussion: (1) low total GSH level can be considered as a novel risk marker for the severity of acute stroke in conditions of low redox status of LMWTs and (2) high Hcy levels associated with low redox status of LMWTs.

Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice

“…At the same time, a statistically significant increase in the expression of the Gclc gene was observed in mice treated with βHB ( Figure 5 C). The product of this gene encodes the first and rate-limiting step of GSH synthesis [ 73 ], the level of which plays a crucial role in the prognosis and dynamics of brain recovery after stroke [ 74 ]. Similarly, βHB contributed to the increased expression of Gpx1 ( Figure 5 A), whose product scavenges H 2 O 2 and uses GSH for this purpose [ 75 ].…”

Neuroprotective Effect of Platinum Nanoparticles Is Not Associated with Their Accumulation in the Brain of Rats

“…In response to cerebral ischemia, there is a rapid decrease in the content of their reduced forms in blood plasma as well as a drop in the redox status of the main intracellular antioxidant (GSH) in the nervous tissue itself [19,20]. GSH has previously been shown to be associated with stroke severity [21]. The important protective role of GSH was also confirmed by the efficacy of using N-acetylcysteine (a readily available substrate for GSH synthesis) in models of ischemia [22,23] and in the treatment of stroke [13].…”

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

“…Glutathione might inhibit the effects of cerebral infarction and enhance antiapoptotic signaling after ischemic stroke, suggesting that GSH may be a potent therapeutic antioxidant that can attenuate severe pathologies after ischemic stroke, and stimulating GSH synthesis through administration of GSH precursors and micronutrients like selenium can optimize GSH and GSH peroxidase for optimal antioxidant defense in cerebral ischemia ( 155 , 156 ). Low total GSH and high homocysteine levels are considered as novel risk markers for acute stroke severity, and low total and reduced GSH levels may be potential risk markers for stroke severity and insufficient functional independence in large-artery atherosclerosis ( 157 , 158 ). Since GSH is the final product of the homocysteine metabolism in the transsulfuration pathway by transferring sulfur from homocysteine to cysteine, a deficiency in transsulfuration pathway leads to excessive homocysteine production (hyperhomocysteinemia) and reduced GSH synthesis ( 159 , 160 ).…”