Coronary artery disease (CAD) and the coronary artery bypass graft (CABG) are associated with a decreased blood glutathione (bGSH) level. Since GSH metabolism is closely related to other aminothiols (homocysteine and cysteine) and glucose, the aim of this study was to reveal the associations of bGSH with glucose and plasma aminothiols in CAD patients (N = 35) before CABG and in the early postoperative period. Forty-three volunteers with no history of cardiovascular disease formed the control group. bGSH and its redox status were significantly lower in CAD patients at admission. CABG had no significant effect on these parameters, with the exception of an increase in the bGSH/hemoglobin ratio. At admission, CAD patients were characterized by negative associations of homocysteine and cysteine with bGSH. All these associations disappeared after CABG. An association was found between an increase in oxidized GSH in the blood in the postoperative period and fasting glucose levels. Thus, CAD is associated with the depletion of the intracellular pool and the redox status of bGSH, in which hyperhomocysteinemia and a decrease in the bioavailability of the extracellular pool of cysteine play a role. The present study indicates that CABG causes disruptions in aminothiol metabolism and induces the synthesis of bGSH. Moreover, glucose becomes an important factor in the dysregulation of GSH metabolism in CABG.

Background/Objectives: The amino acid cysteine (Cys) plays an important role in the neuronal injury process in stroke. Cys is present in blood plasma in various forms. The relationship between Cys and its forms and the severity of acute stroke has not been sufficiently studied. We investigated the levels of total Cys and two of its forms (reduced Cys and its disulfide (cystine, CysS)) in blood plasma and their influence on stroke severity in patients at admission. Methods: A total of 210 patients (39–59 years old) with ischemic stroke and intracerebral or subarachnoid hemorrhage were examined. The contents of the different forms of Cys were determined in the first 10–72 h. Stroke severity was estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRs). Results: CysS levels < 54 μM were associated with severe (NIHSS > 13) neurological deficit (ischemic stroke: RR = 5.58 and p = 0.0021; hemorrhagic stroke: RR = 3.56 and p = 0.0003). Smoking and high levels of total Cys and other thiols (glutathione and homocysteine) appear to be factors determining this relationship. Conclusions: Low CysS levels may serve as a potential biomarker of acute stroke severity.

Background/Objectives: The amino acid cysteine (Cys) plays an important role in the neuronal injury process in stroke. Cys is present in blood plasma in various forms. The relationship between Cys and its forms and the severity of acute stroke has not been sufficiently studied. We investigated the total Cys and the levels of two of its forms (reduced Cys and its disulfide (cystine, CysS)) in blood plasma and the influence on stroke severity in patients at admission. Methods: A total of 210 patients (39-59 years old) with ischemic stroke and intracerebral or subarachnoid hemorrhage were examined. The content of the different forms of Cys was determined in the first 10–72 h. Stroke severity was estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRs). Results: CysS levels < 54 μM were associated with severe (NIHSS>13) neurological deficit (ischemic stroke: RR=5.58, p=0.0021; hemorrhagic stroke: RR=3.56, p=0.0003). Smoking and high levels of total Cys and other thiols (glutathione and homocysteine) appear to be factors determining this relationship. Conclusions: Low CysS levels may act as a potential biomarker of acute stroke severity.

For a comprehensive study of such a socially significant disease as multiple sclerosis (MS), which occurs predominantly in people of working age and in which neuroinflammation and neurodegeneration go hand in hand, resulting in irreversible damage to the brain and spinal cord, the key point is to decipher the pathophysiological mechanisms of its development and progression. Despite the established relationship between hyperhomocysteinemia and secondary endothelial damage, data on the possible role of homocysteine (Hcy) in disease progression are quite contradictory.Objective: to investigate the informative value of determining the content of markers of oxidative stress, mitochondrial and endothelial dysfunction in patients with MS.Material and methods. The study included 63 patients with MS (40 women, 23 men) aged 35 [30; 43] years. The control group consisted of 43 healthy volunteers (22 men, 21 women) aged 37 [32; 44] years. Depending on the therapy received, patients were divided into two groups: those receiving first-line and second-line therapy; patients receiving natalizumab therapy were considered separately. A neurological examination of patients was performed with an assessment of disease severity using the EDSS scale, and the disease progression index was calculated. The following biomarkers were also determined in the blood of patients and volunteers using enzyme-linked immunosorbent assay: intercellular adhesion molecules (ICAM-1), S-adenosylmethionine, S-adenosylhomocysteine, cysteine, cysteinylglycine, glutathione, and Hcy.Results. A statistically significant correlation was found between disease severity (EDSS disability level) and increased Hcy levels. A statistically significant increase in ICAM-1 levels was also found in patients during periods of disease activity (clinical exacerbation, activity according to MRI data), which allows this molecule to be considered as a biomarker of endothelial dysfunction and inflammation.Conclusion. The results of the study indicate the need to continue studying the pathophysiological causes of the onset and progression of MS, further identifying new biomarkers for predicting the course of MS, and evaluating the effectiveness of drugs that alter the course of MS.

Background/Objectives: Glutathione (GSH) and its precursor cysteine (Cys) plays an important role in the neuronal injury process in stroke. We evaluate the association of cysteine and glutathione forms in blood plasma with the severity and disability of acute hemorrhagic stroke. Methods: A total of 64 patients (39-59 years old) with intracerebral (n=12) or subarachnoid hemorrhage (n=52) were examined. The patients' conditions were estimated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). Results: The median levels of plasma cystine (CysS) and reduced glutathione (rGSH) were 51.1 and 1.04 µM, respectively. Patients with high levels (≥50 μM) of CysS had a significantly higher frequency of mild or moderate neurological impairment (NIHSS≤10) than patients with levels of CysS<50 µM (OR=7.73, CI95% 2.19-27.28). Also, patients with high levels (≥1.9 μM) of rGSH had a significantly higher frequency of mild disability (mRS≤2) compared to patients with rGSH<1.9 µM (OR=12.35, CI95% 3.43-44.5). Conclusions: CysS and rGSH levels are associated with a reduced risk of high neurological deficit and disability, respectively, in the acute period of hemorrhagic stroke. These indicators could be used to evaluate neurologic impairment severity of stroke patient. Further research is needed to determine potential of circulating free thiols as biomarkers and to evaluate the usefulness of GSH-targeting therapy in acute hemorrhagic stroke.

Polysulfides play an important role in regulating many physiological processes, making their study relevant in health and disease. This study aims to improve their evaluation method by determining alkaline-labile sulfane sulfur (ALSS) and to test it on various biological samples, as well as on models of hyperhomocysteinemia and oxidative/reductive stress. The ALSS assay is based on the photometric determination of H₂S, which is generated from polysulfides under alkaline conditions. The limit of quantitative detection was 3.3 nmol, interday reproducibility was 5.7% (blood plasma), and the yields of H₂S precipitation and product extraction were 97.8 and 89.7%, respectively. The specificity of the approach, determined with two different methods of sulfide destruction, was 80% on a model mixture of bovine albumin or blood plasma. A small but noticeable matrix effect was revealed. ALSS of control rats (n = 15) and human plasma (n = 10) was 133 (128; 135) and 177.6 (171.8; 183.6) μmol/g protein, respectively. Decreased ALSS levels were observed in rats with mild hyperhomocysteinemia (n = 14) and in patients with acute stroke (n = 20). Under 24h oxidative stress, ALSS decreased from 14.8 ± 1.3 to 10.4 ± 1.0 μmol/g protein (p = 0.0055) in the THP-1 culture, while 96h reductive stress caused it to increase from 10.9 ± 0.9 to 15.9 ± 2.0 μmol/g protein, p = 0.00034. The method presented in this paper allows for the assessment of ALSS in various biological matrices and has demonstrated sensitivity to oxidative stress in vitro and hyperhomocysteinemia in vivo. This makes it a promising indicator of sulfur metabolism disorders in pathological conditions.