Blood Glutathione S-Transferase-π as a Time Indicator of Stroke Onset

Abstract

BackgroundAbility to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures.MethodsThe blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances.ResultsAmong the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103).ConclusionsThis study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.

Activities of Three Erythrocyte Enzymes of Hyperglycemic Rats (Rattus norvegicus) Treated with Allium sativa Extract.

“…Erythrocyte GST activity has been proven to be a reliable biochemical index and the basis for diagnosis and monitoring of therapeutic events in the course of treatment and management of other pathologic/metabolic disorders whose etiologies and manifestations are linked to oxidative stress. Notable among which are: parasitic infections, [26,54] gout and rheumatoid arthritis, [55,56] haemoglobinopathies, [26] malignancy, [57] hypertension, [58] stroke [59] and atherosclerosis. [60] In a related perspective, the use of GT activity as a reliable biomarker in depicting the etiology of diabetes mellitus has been described.…”

Protective Effects of Brain Infarction by N -Acetylcysteine Derivatives

“…It has been reported that acrolein conjugation with glutathione is catalyzed by glutathione-S-transferases (GSTs), 20 and major GSTs in brain are GST-π, -θ, and -μ. 21,22 Accordingly, the levels of GST-π, -θ, and -μ were estimated by Western blotting. When brain tissue was damaged by ischemia, the levels of GSTs decreased to ≈50% of normal tissue (Figure 4).…”

Diagnostic performance of peroxiredoxin 1 to determine time-of-onset of acute cerebral infarction

“…While cerebrovascular biomarkers are widely used to diagnose, define the severity and predict the prognosis of patients with cerebral ischemia12, only one study has assessed their kinetics at the acute phase of stroke3. However, this could be an interesting field of research as many proteins are synthetized, released and activated at the acute phase of stroke.…”

“…observed the presence of high levels of two enzymes involved in oxidative stress, peroxiredoxin 1 (PRDX1) and glutathione s-transferase π (GST-π), in the blood of patients with cerebral infarction6. Moreover, GST-π levels were found to be associated with stroke onset in a prospective cohort of patients with acute ischemic stroke3. In the same cohort, we studied the kinetics of PRDX1 at the acute phase of cerebral infarction and its diagnostic performance to identify cerebral infarction of less than 3 and 6 hours.…”

“…In the same cohort, we studied the kinetics of PRDX1 at the acute phase of cerebral infarction and its diagnostic performance to identify cerebral infarction of less than 3 and 6 hours. We also assessed the diagnostic performance of a PRDX1/GST-π panel using GST-π values determined during our previous study3.…”