Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice
Table 2
Salivary redox and inflammatory biomarkers in stroke patients.
Study design
Results
References
Study group
Control group
Smokers/PD
Saliva collection
NWS (vs. control group)
SWS (vs. control group)
Comments
Redox biomarkers
30 patients (18 men and 12 women) with acute hemorrhagic (30%) and ischemic (70%) stroke
30 age- and sex-matched healthy controls
No/no
NWS: expectorating saliva (for 15 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 20 min) SWS: citric acid (2%) stimulation every 30 s for 5 min, expectorating saliva (for 5 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 20 min)
Comparison of hemorrhagic and ischemic stroke: no statistical differences between hemorrhagic and ischemic stroke Correlation analysis: GSH SWS correlated positively with dynamic balance abilities in BBS and cognitive function in the ACE III scale; AGE SWS, AOPP SWS, and LOOH SWS correlated negatively with the salivary flow rate Multifactorial regression analysis: GSH SWS does not depend on gender, age, and salivary flow rate ROC analysis: GSH SWS with sensitivity and specificity equal to 100% differentiates the study group from controls (AUC 1.0); high diagnostic utility is also shown by NWS AOPP (sensitivity 83.33%, specificity 76.67%, AUC 0.8711), NWS LOOH (sensitivity 86.67%, specificity 80%, AUC 0.8567), SWS TOS (sensitivity 86.67%, specificity 83.33%, AUC 0.8822), SWS AOPP (sensitivity 96.67%, specificity 93.33%, AUC 0.9911), and SWS LOOH (sensitivity 93.33%, specificity 90%, AUC 0.9833)
30 patients (19 men and 11 women) with acute hemorrhagic (20%) and ischemic (80%) stroke divided into two subgroups taking into consideration the rate of salivary secretion: normal salivary secretion () and hyposalivation ()
30 age- and sex-matched healthy controls with normal salivary secretion (NWS mL/min)
No/no
NWS: expectorating saliva (for 15 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 20 min) SWS: citric acid (2%) stimulation every 30 s for 5 min, expectorating saliva (for 5 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 20 min)
Protein glycation: ↑Amadori products, ↑AGE (colorimetric/fluorimetric methods) Protein oxidation: ↑PC, ↓total thiols (colorimetric methods) Protein glycoxidation: ↑dityrosine, ↑kynurenine, ↑N-formylkynurenine, ↓tryptophan (colorimetric/fluorimetric methods) Nitrosative stress: ↓NO, ↑peroxynitrite, ↑nitrotyrosine (colorimetric method/ELISA)
Protein glycation: ↑Amadori products, ↑AGE (colorimetric/fluorimetric methods) Protein oxidation: ↓total thiols (colorimetric methods) Protein glycoxidation: ↑N-formylkynurenine, ↓tryptophan (colorimetric/fluorimetric methods) Nitrosative stress: ↑peroxynitrite (colorimetric method)
General comments: protein glycation (NWS: ↑Amadori products, ↑AGE; SWS: ↑AGE), glycoxidation (NWS: ↑dityrosine), and nitrosative stress (NWS: ↓NO, ↑nitrotyrosine; SWS: ↑peroxynitrite) were significantly increased in stroke patients with hyposalivation when compared to stroke cases with normal salivary secretion Comparison of hemorrhagic and ischemic stroke: no statistical differences between hemorrhagic and ischemic stroke Comparison of NWS and SWS: the content of protein glycation, oxidation and glycoxidation products as well as nitrosative stress biomarkers was significantly higher in NWS compared to SWS in both control and stroke patients Correlation analysis: NWS Amadori products, NWS AGE, NWS PC, NWS dityrosine, NWS kynurenine, NWS N-formylkynurenine, NWS NO, and NWS nitrotyrosine correlated negatively with the salivary flow rate; NWS total thiols correlated positively with the NWS flow. Such changes were not observed in SWS of stroke patients
Study group: 50 patients (24 men and 26 women) with ischemic stroke Risk groups: 25 patients (12 men and 13 women) with hypertension; 25 patients (11 men and 14 women) with type 2 diabetes
25 age- and sex-matched healthy controls (12 men and 13 women)
ND/no
Expectorating saliva (for 5 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 5 min)
Serum analysis: ↑SOD, ↑UA, ↓GSH, ↑MDA vs. control group ROC analysis: salivary MDA with a higher accuracy rate (92%) than that of serum values (81%) differentiates healthy individuals from those with ischemic stroke (salivary AUC 0.969, serum AUC 0.885); high diagnostic utility is also shown by salivary (accuracy 89.3%, AUC 0.95) and serum (accuracy 89.3%, AUC 0.927) UA, salivary (accuracy 89.3%, AUC 0.918) and serum (accuracy 80%, AUC 0.838) SOD, and salivary (accuracy 81%, AUC 0.669) and serum (accuracy 80%, AUC 0.912) GSH Prediction analysis: for predicting stroke in diabetic patients, the most valid parameters are salivary UA (AUC 0.709) and salivary SOD (AUC 0.679); the most valid parameters in predicting ischemic stroke from ischemic heart disease are salivary UA (AUC 0.66) and salivary GSH (AUC 0.623); to differentiate stroke from the whole risk group, the most valid parameters are salivary MDA (AUC 0.705) and salivary SOD (AUC 0.661)
Study group: 50 patients (24 men and 26 women) with ischemic stroke Risk groups: 25 patients (12 men and 13 women) with hypertension; 25 patients (11 men and 14 women) with type 2 diabetes
25 age- and sex-matched healthy controls (12 men and 13 women)
ND/no
Expectorating saliva (for 5 min) into a test tube placed in a receptacle containing ice, centrifugation (, 4°C, 5 min)
↑NSE (ELISA)
Serum analysis: ↑NSE vs. control ROC analysis: salivary NSE differentiates stroke patients with controls (AUC 0.763) as well as stroke cases from negative controls (patients with hypertension and type 2 diabetes; AUC 0.825)
