Increased Root Canal Endotoxin Levels are Associated with Chronic Apical Periodontitis, Increased Oxidative and Nitrosative Stress, Major Depression, Severity of Depression, and a Lowered Quality of Life

Abstract

Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), -sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physio-somatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing hypernitrosylation and thus neuroprogressive processes. Dental health and "leaky teeth" may be intimately linked to the etiology and course of depression, while significantly impacting quality of life.

Lowered quality of life in mood disorders is associated with increased neuro‐oxidative stress and basal thyroid‐stimulating hormone levels and use of anticonvulsant mood stabilizers

“…The first major finding of this study is that MDA, AOPP, the nitro‐oxidative stress index, and lowered CMPAase activity are associated with the different HRQoL domains, especially with physical and social relationships. We are not aware of any studies showing a relationship between MDA and HRQoL in mood disorders, while a prior study found AOPP to be inversely associated with HRQoL in patients with depression due to periodontitis . In women with postmenopausal osteoporosis, HRQoL subdomains, including pain and mental and social functions, correlate with NO levels and antioxidant enzyme activities, but not MDA .…”

“…In women with postmenopausal osteoporosis, HRQoL subdomains, including pain and mental and social functions, correlate with NO levels and antioxidant enzyme activities, but not MDA . Increased MDA levels are detected in MDD, BD, patients with prior suicidal attempts, severe depression, TUD, and metabolic syndrome, while increased levels of AOPP are detected in suicide, major depression, and prenatal depression . Increased MDA and AOPP levels are oxidative damage biomarkers, which may cause (neuro)degenerative processes including arteriosclerosis and neurodegeneration, which both may be linked to lowered HRQoL scores.…”

“…Activated neuro‐oxidative pathways promote neurotoxicity, excitotoxicity, apoptosis, attenuated neurogenesis, and autoimmunity . Moreover, major depression is associated with increased levels of advanced oxidation protein products (AOPP) indicating peroxynitrite and hypochlorous acid–induced protein oxidation . In patients with mood disorders, lowered activity levels of paraoxonase/CMPAase (PON1), an antioxidant enzyme, are inversely associated with HRQoL …”

Effects of alpha‐lipoic acid therapy on experimentally induced apical periodontitis: a biochemical, histopathological and micro‐CT analysis

“…Another study demonstrated that increased root canal endotoxin levels were associated with increased oxidative stress, severity of depression, and a lowered quality of life (Gomes et al . ).…”

Upregulation of the Nitrosylome in Bipolar Disorder Type 1 (BP1), but not BP2, and Major Depression: Increased IgM Antibodies to Nitrosylated Conjugates are Associated with Indicants of Leaky Gut

“…It should be underscored that MDD and BP disorder are characterized by reduced -SH groups and glutathione levels in serum or brain. [33][34] By inference, MDD and BP1, but not BP2, appear to be associated with increased production of NO metabolites which may induce increased nitrosylation, which in turn may damage both the glutathione system and SH-groups thereby attenuating key components of the antioxidant defense. These findings further extent our recent report that the (partially) remitted phase of MDD and BP1, but not BP2, is accompanied by increased signs of nitro-oxidative stress and breakdown of antioxidant defenses.…”