Plasma glutathione as a risk marker for the severity and functional outcome of acute atherothrombotic and cardioembolic stroke

Abstract

Objective Glutathione (GSH) is a major intracellular thiol-containing antioxidant. We tried to determine whether blood plasma GSH level is a marker for the severity of the two subtypes of acute stroke (large-artery atherosclerosis, LA and cardioembolic, CE). Forty-three patients with LA and 36 patients with CE aged 65 (47–82) years were included in the study. Thirty-one patients with cerebral microangiopathy were included for comparison. Total (t) and reduced (r) GSH levels were determined at admission. Neurological deficit was assessed by the National Institutes of Health Stroke Scale (NIHSS) on the first day, functional outcome and independence were assessed by the modified Rankin scale (mRs) and Bartel index (BI), respectively, after 21 days. Results The tGSH and rGSH levels in acute stroke were significantly lower than cerebral microangiopathy patients. Low tGSH (≤ 1.45 μM) and rGSH (≤ 30 nM) levels were risk markers for stroke severity at admission (NIHSS > 10) in patients with LA: age and gender adjusted odds ratio (AOR) was 4.95, 95% coincidence interval (CI) 1.31–18.7, AOR = 9.141, CI 1.84–45.3 for t- and rGSH, respectively. A low level of rGSH (≤ 30 nM) was found as risk marker for functional independence (BI ≤ 60: AOR = 15.9, CI 2.22–114.2) in patients with LA. Low tGSH level (≤ 1.1 μM) was associated with the reduction of poor outcome risk (mRs > 2: AOR = 0.154, CI 0.029–0.809) in CE group. Conclusions Low t- and rGSH levels may be considered potential risk markers for severity and insufficient functional independence in LA. Conversely, low tGSH level reduce the risk of poor stroke outcome only for CE.

The Role of Glutathione in Prevention of COVID-19 Immunothrombosis: A Review

“…Glutathione has been found to be directly related to thrombosis and thrombotic events through many mechanisms, generally related to platelet attenuation and activity on the coagulation cascade [ 23 , 24 ]. GSH is utilized by glutathione peroxidase (GPX) to reduce free hydrogen peroxide and lipid hyperoxides.…”

“…GSH is a low molecular weight aminothiol, protecting other cellular thiols from oxidative damage, and helping reduce reactive oxygen species the cell is exposed to. In addition to this it is heavily involved in platelet attenuation [ 23 ].…”

The Role of Potential Oxidative Biomarkers in the Prognosis of Acute Ischemic Stroke and the Exploration of Antioxidants as Possible Preventive and Treatment Options

“…Over 90% of total glutathione (GSH) is in the reduced form (GSH). In the brain, glutathione is mainly in a reduced form in high concentration (~1–3 mM) [ 158 , 159 , 160 ]. In two experimental rat models of ischemia caused by hypoperfusion (middle cerebral artery occlusion and bilateral occlusion of the common carotid arteries), GSH homeostasis as an oxidative stress marker has been disturbed in global and focal ischemia.…”

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 ).…”