Oxidative stress plays a crucial role in dementia pathogenesis; however, its impact on salivary secretion and salivary qualities is still unknown. This study included 80 patients with moderate dementia and 80 healthy age- and sex-matched individuals. Salivary flow, antioxidants (salivary peroxidase, catalase, superoxide dismutase, uric acid and total antioxidant capacity), and oxidative damage products (advanced oxidation protein products, advanced glycation end products (AGE), 8-isoprostanes, 8-hydroxy-2’-deoxyguanosine and total oxidant status) were estimated in non-stimulated and stimulated saliva, as well as in plasma and erythrocytes. We show that in dementia patients the concentration/activity of major salivary antioxidants changes, and the level of oxidative damage to DNA, proteins and lipids is increased compared to healthy controls. Non-stimulated and stimulated salivary secretions were significantly reduced in dementia patients. The deterioration in mini mental state examination (MMSE) score correlated with salivary AGE levels, which when considered with receiver operating characteristic (ROC) analysis, suggests their potential role in the non-invasive diagnosis of dementia. In conclusion, dementia is associated with disturbed salivary redox homeostasis and impaired secretory function of the salivary glands. Salivary AGE may be useful in the diagnosis of dementia.
This study is the first to evaluate oxidative stress biomarkers in saliva/blood of patients with varying degrees of dementia progression. The study included 50 healthy controls and 50 dementia patients divided into two groups: those with mild and moderate dementia (MMSE 11–23) and patients suffering from severe dementia (MMSE 0–10). Cognitive functions of the subjects were assessed using the Mini Mental State Examination (MMSE). Enzymatic and non-enzymatic antioxidants, oxidative damage products and protein glycoxidative modifications were determined in non-stimulated (NWS) and stimulated (SWS) saliva as well as erythrocyte/plasma samples. Generally, in dementia patients, we observed the depletion of antioxidant defences leading to oxidative and glycoxidative damage in NWS, SWS and blood samples. Both salivary and blood oxidative stress increased with the severity of the disease, and correlated with a decrease of cognitive functions. Interestingly, in dementia patients, reduced glutathione (GSH) in NWS correlated not only with the severity of dementia, but also with GSH concentration in the plasma. In receiver operating characteristic (ROC) analysis, we have demonstrated that salivary GSH clearly distinguishes patients with severe dementia from those suffering from mild or moderate dementia (area under the curve (AUC) = 1). Therefore, salivary GSH can be used as a non-invasive biomarker of cognitive impairment.
Our results confirm that antipsychotic medication modifies brain metabolism measured by means of ¹H MRS. The pattern of the changes suggests a neuroprotective action of antipsychotic medication in schizophrenia.
Major Depressive Disorder (MDD) is a leading cause of disability worldwide, creating a high medical and socioeconomic burden. There is a growing interest in the biological underpinnings of depression, which are reflected by altered levels of biological markers. Among others, enhanced inflammation has been reported in MDD, as reflected by increased concentrations of inflammatory markers—C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble interleukin-2 receptor. Oxidative and nitrosative stress also plays a role in the pathophysiology of MDD. Notably, increased levels of lipid peroxidation markers are characteristic of MDD. Dysregulation of the stress axis, along with increased cortisol levels, have also been reported in MDD. Alterations in growth factors, with a significant decrease in brain-derived neurotrophic factor and an increase in fibroblast growth factor-2 and insulin-like growth factor-1 concentrations have also been found in MDD. Finally, kynurenine metabolites, increased glutamate and decreased total cholesterol also hold promise as reliable biomarkers for MDD. Research in the field of MDD biomarkers is hindered by insufficient understanding of MDD etiopathogenesis, substantial heterogeneity of the disorder, common co-morbidities and low specificity of biomarkers. The construction of biomarker panels and their evaluation with use of new technologies may have the potential to overcome the above mentioned obstacles.
Stress, anxiety and depressive disorders are often characterized by the activation of the stress axis, which results in similar symptoms at some point in these disorders. These disorders are closely related to each other—they occur simultaneously or follow one another. The diagnosis of stress, anxiety and depression is not a perfect procedure currently—it is based on patient observation and an interview with the patient and their family. There are no laboratory tests that would dispel the doubts of the doctor making the diagnosis and allow the appropriate treatment to be implemented as soon as possible. Therefore, this study will review the components of saliva that could be helpful in the quick diagnosis of stress, anxiety and/or depression. Such potential salivary biomarkers could also be useful in monitoring the effectiveness of pharmacological treatment prescribed by a psychiatrist. The following are promising salivary biomarkers of stress, anxiety or depression: cortisol, immunoglobulin A (sIgA), lysozyme, melatonin, α-amylase (sAA), chromogranin A (CgA) and fibroblast growth factor 2 (FGF-2). To the best valuable potential salivary markers of stress, we can include cortisol, lysozyme, sAA and CgA. To differentiate depression from stress, salivary cortisol and melatonin can be helpful. Fluctuations in the concentrations of the above-mentioned substances in saliva indicate a particularly strong relationship with typical human psychological problems, such as stress, depression or anxiety.
Up to 30% of all hospital admissions and health-care costs may be attributable to alcohol abuse. Ethanol, its oxidative metabolites, acetaldehyde and ROS (reactive oxygen species), non-oxidative metabolites of alcohol [e.g. FAEEs (fatty acid ethyl esters)] and the ethanol-water competition mechanism are all involved in the deregulation of glycoconjugate (glycoprotein, glycolipid and proteoglycan) metabolic processes including biosynthesis, modification, transport, secretion, elimination and catabolism. An increasing number of new alcohol biomarkers that are the result of alcohol-induced glycoconjugate metabolic errors have appeared in the literature. Glycoconjugate-related alcohol markers are involved in, or are a product of, altered glycoconjugate metabolism, e.g. CDT (carbohydrate-deficient transferrin), SA (sialic acid), plasma SIJ (SA index of apolipoprotein J), CETP (cholesteryl ester transfer protein), β-HEX (β-hexosaminidase), dolichol, EtG (ethyl glucuronide) etc. Laboratory tests based on changes in glycoconjugate metabolism are useful in settings where the co-operativeness of the patient is impaired (e.g. driving while intoxicated) or when a history of alcohol use is not available (e.g. after trauma). In clinical practice, glycoconjugate markers of alcohol use/abuse let us distinguish alcoholic from non-alcoholic tissue damage, having important implications for the treatment and management of diseases.
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