Salivary Xanthine Oxidase as a Potential Biomarker in Stroke Diagnostics

Abstract

Stroke is one of the most common cerebrovascular diseases. Despite significant progress in understanding stroke pathogenesis, cases are still increasing. Thus, laboratory biomarkers of stroke are sought to allow rapid and non-invasive diagnostics. Ischemia-reperfusion injury is an inflammatory process with characteristic cellular changes leading to microvascular disruption. Several studies have shown that hyperactivation of xanthine oxidase (XO) is a major pathogenic factor contributing to brain dysfunction. Given the critical role of XO in stroke complications, this study aimed to evaluate the activity of the enzyme and its metabolic products in the saliva of stroke subjects. Thirty patients in the subacute phase of stroke were included in the study: 15 with hemorrhagic stroke and 15 with ischemic stroke. The control group consisted of 30 healthy subjects similar to the cerebral stroke patients regarding age, gender, and status of the periodontium, dentition, and oral hygiene. The number of individuals was determined a priori based on our previous experiment (power of the test = 0.8; α = 0.05). The study material was mixed non‐stimulated whole saliva (NWS) and stimulated saliva (SWS). We showed that activity, specific activity, and XO output were significantly higher in NWS of ischemic stroke patients than in hemorrhagic stroke and healthy controls. Hydrogen peroxide and uric acid levels were also considerably higher in NWS of ischemic stroke patients. Using receiver operating curve (ROC) analysis, we demonstrated that XO-specific activity in NWS distinguishes ischemic stroke from hemorrhagic stroke (AUC: 0.764) and controls (AUC: 0.973) with very high sensitivity and specificity. Saliva collection is stress-free, requires no specialized medical personnel, and allows continuous monitoring of the patient’s condition through non-invasive sampling multiple times per day. Salivary XO also differentiates with high accuracy (100%) and specificity (93.75%) between stroke patients with mild to moderate cognitive decline (AUC = 0.988). Thus, salivary XO assessment may be a potential screening tool for a comprehensive neuropsychological evaluation. To summarize, our study demonstrates the potential utility of salivary XO in the differential diagnosis of stroke.

Could inflammation contribute to salivary gland dysfunction in patients with chronic heart failure?

“…They also had not taken any medications at least 8 hours before saliva collection. After rinsing the mouth twice with room-temperature distilled water, patients spat out saliva accumulated at the bottom of the mouth, for 15 minutes, into a sterile centrifuge tube placed in a container with ice ( 23 ). The volume of saliva was measured with a single-channel pipette with accuracy of 100 μL and was the basis for calculating the salivary flow rate (SFR; mL/min).…”

“…Instruments, Warsaw, Poland), and plasma was collected for assays. The antioxidant butylated hydroxytoluene (BHT) was added to the samples ( 23 ). Samples were stored at -80°C for no longer than six months.…”

“…Hyposalivation was defined as saliva flow rate (SFR) below 0.2 mL/min (23)(24)(25)(26). Based on SFR, patients with HF were divided into two groups: a group with normal salivation (NS) and one with reduced saliva secretion (hyposalivation, HS).…”

The clinical value of serum xanthine oxidase levels in patients with acute ischemic stroke

“…A basic study reported that in a rat model of AIS, XO expression on the infarcted side was significantly higher than that on the noninfarcted side and continued to increase over time [ 18 ]. A recent study conducted by Mateusz M et al indicated that salivary XO may be a potential biomarker for the diagnosis of stroke, which provides a new simple strategy for early prediction in patients with AIS [ 19 ]. However, few studies have confirmed the clinical value of serum XO levels in the pathogenesis of AIS [ 20 ].…”

SARS-CoV-2 reliably detected in frozen saliva samples stored up to one year

“…Saliva samples are utilized in various diagnostic assays, including COVID-19 [1][2][3][4]. During the COVID-19 pandemic, large biobanks were started to provide clinical samples for several different studies, including pivotal validation assays needed to obtain regulatory clearance for new diagnostic tests.…”