Salivary Redox Biomarkers in Insulin Resistance: Preclinical Studies in an Animal Model

Abstract

Insulin resistance (IR) is a condition of impaired tissue response to insulin. Although there are many methods to diagnose IR, new biomarkers are still being sought for early and noninvasive diagnosis of the disease. Of particular interest in laboratory diagnostics is saliva collected in a stress-free, noninvasive, and straightforward manner. The purpose of the study was to evaluate the diagnostic utility of salivary redox biomarkers in preclinical studies in an animal model. The study was conducted on 20 male Wistar rats divided into two equal groups: a standard diet and a high-fat diet (HFD). In all rats fed the HFD, IR was confirmed by an elevated homeostasis model assessment (HOMA-IR) index. We have shown that IR is responsible for the depletion of the enzymatic (↓superoxide dismutase) and nonenzymatic (↓ascorbic acid, ↓reduced glutathione (GSH)) antioxidant barrier at both the central (serum/plasma) and salivary gland (saliva) levels. In IR rats, we also demonstrated significantly higher concentrations of protein/lipid oxidation (↑protein carbonyls, ↑4-hydroxynoneal (4-HNE)), glycation (↑advanced glycation end products), and nitration (↑3-nitrotyrosine) products in both saliva and blood plasma. Salivary nonenzymatic antioxidants and oxidative stress products generally correlate with their blood levels, while GSH and 4-HNE have the highest correlation coefficient. Salivary GSH and 4-HNE correlate with body weight and BMI and indices of carbohydrate metabolism (glucose, insulin, HOMA-IR) and proinflammatory adipokines (leptin, resistin, TNF-α). These biomarkers differentiate IR from healthy controls with very high sensitivity (100%) and specificity (100%). The high diagnostic utility of salivary GSH and 4-HNE is also confirmed by multivariate regression analysis. Summarizing, saliva can be used to assess the systemic antioxidant status and the intensity of systemic oxidative stress. Salivary GSH and 4-HNE may be potential biomarkers of IR progression. There is a need for human clinical trials to evaluate the diagnostic utility of salivary redox biomarkers in IR conditions.

Salivary biomarkers: novel noninvasive tools to diagnose chronic inflammation

“…The authors showed an impairment in antioxidant barriers and in ROS scavengers both in plasma and in saliva, proven by the reduction in superoxide dismutase, ascorbic acid and glutathione (GSH) levels in IR mice. 158 These alterations were paralleled by strengthened lipid/protein oxidation and advanced glycation end products in both biological fluids, showing an elevated coefficient of correlation between the two.…”

The Emerging Role of Salivary Oxidative Stress Biomarkers as Prognostic Markers of Periodontitis: New Insights for a Personalized Approach in Dentistry

“…Tobacco is an exogenous origin of ROS [ 14 ]. In diabetic patients, the resistance to insulin causes a decrease in antioxidants and, as a response to the system, ROS concentration increases [ 74 ]. In cardiovascular disease, it was seen an association with periodontitis.…”

Metabolic Priming as a Tool in Redox and Mitochondrial Theragnostics

“…For example, salivary GSH and 4-hydroxynonenal (4-HNE), products of lipid peroxidation, can be potential biomarkers to measure the degree of systemic oxidative stress in patients with insulin resistance, although additional validation is needed to confirm their diagnostic efficacy [221]. Advanced oxidation protein products (AOPPs), oxidized free cysteine, tumor necrosis factor receptor-1 (TNFR1), and osteopontin are promising biomarkers associated with the loss of estimated glomerular filtration rate (eGFR) in immunoglobulin A (IgA) nephropathy, a kidney disease also known as Berger's disease.…”