Salivary Biomarkers of Oxidative Stress and Inflammation in Stroke Patients: From Basic Research to Clinical Practice

Abstract

Cerebral stroke is a serious worldwide health problem, as can be seen by the global epidemic of the disease. In this disorder, when the blood flow is compromised by ruptures or blocked arteries, sudden death of neurons is observed as a result of a lack of oxygen and nutrients. Numerous severe problems and frequent complications also exist in stroke patients; therefore, there is an urgent need to develop new therapeutic, diagnostic, and prognostic methods for the disease. At present, the diagnosis of stroke is based on a neurological examination, medical history, and neuroimaging, due to the fact that rapid and noninvasive diagnostic tests are unavailable. Nevertheless, oxidative stress and inflammation are considered key factors in stroke pathogenesis. Oxygen free radicals are responsible for oxidation of lipids, proteins, and DNA/RNA, which in turn contributes to oxidative damage of the brain. Toxic products of the oxidation reactions act cytostatically on the cell by damaging cell membranes and leading to neuronal death by apoptosis or necrosis. Thus, it seems that redox/inflammatory biomarkers might be used in the diagnosis of the disease. Nowadays, saliva is of increasing interest in clinical laboratory medicine. Redox biomarkers could be obtained easily, noninvasively, cheaply, and stress-free from saliva. This minireview is aimed at presenting the current knowledge concerning the use of salivary biomarkers of oxidative stress and inflammation in the diagnosis and prognosis of stroke.

Figure 1

Redox imbalance in stroke brain. In stroke patients, there is an increased production of superoxide radical and peroxynitrite, which leads to intensified oxidative and nitrosative brain damage. This condition results not only in the increased synthesis/secretion of proinflammatory cytokines but also in blood-brain barrier (BBB) disruption and enhanced neuronal apoptosis. Abbreviations: CAT: catalase; GPx: glutathione peroxidase; GSH: reduced glutathione; GSSG: oxidized glutathione; SOD: superoxide dismutase.

Figure 2

Transport of antioxidants and cellular oxidation products from the brain to the saliva. Antioxidants (green molecules) as well as protein, lipid, and DNA oxidation products (pink molecules) are transported to the salivary glands via an intracellular or extracellular route. The intracellular route includes passive transport (diffusion, filtration, and facilitated diffusion) and energy-demanding transport (active transport), while the extracellular route occurs by ultrafiltration or through damaged cellular membranes.

Figure 3

Saliva as a source of redox/inflammatory biomarkers in stroke patients. Recent reports indicate the usefulness of salivary redox biomarkers in many systemic diseases, including ischemic and hemorrhagic stroke. Saliva secreted by the parotid, submandibular, and sublingual glands is a plasma filtrate that is rich in antioxidants and cellular oxidation products. In general, concentrations of many redox biomarkers in saliva reflect their levels in blood.