Blood Biomarkers Linked to Oxidative Stress and Chronic Inflammation for Risk Assessment of Colorectal Neoplasia

Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.

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Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening

International Journal of Molecular Sciences ◽

10.3390/ijms222212536 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12536

Author(s):

Szymon Turkiewicz ◽

Marta Ditmer ◽

Marcin Sochal ◽

Piotr Białasiewicz ◽

Dominik Strzelecki ◽

...

Keyword(s):

Oxidative Stress ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Circadian Clock ◽

Chronic Inflammation ◽

Cellular Senescence ◽

Molecular Mechanisms ◽

Telomere Shortening ◽

Age Related ◽

Obstructive Sleep

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

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Metabolic markers and oxidative stress in children’s obesity pathogenesis

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2020-65-1-22-29 ◽

2020 ◽

Vol 65 (1) ◽

pp. 22-29

Author(s):

O. V. Povarova ◽

E. A. Gorodetskaya ◽

E. I. Kalenikova ◽

O. S. Medvedev

Keyword(s):

Oxidative Stress ◽

Adipose Tissue ◽

Chronic Inflammation ◽

Metabolic Disorders ◽

Mineral Metabolism ◽

Related Factors ◽

Metabolic Markers ◽

Hormonal Function ◽

The Moment ◽

Relationship Of

The article presents a modern view of obesity as a chronic inflammation of adipose tissue. Obesity is accompanied by metabolic changes in lipid, protein, carbohydrate, mineral metabolism and disorders in the hormonal function of adipose tissue as an endo- and paracrine organ. At the moment, there are searched the biochemical markers of metabolic disorders of obesity. The obesity-related factors (hyperglycemia, increased lipid levels, insulin resistance, chronic inflammation, hyperleptinemia, endothelial dysfunction, impaired respiratory function of mitochondria, minerals and microelements deficiency) form and increase oxidative stress making it an integral component of the pathogenesis of obesity and possible complications. Given the important role of Q10 coenzyme in antioxidant tissue protection, the authors discuss the relationship of obesity and metabolic disorders to the endogenous levels of Q10 coenzyme and its possible use for pharmacological correction.

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Oxidative stress inactivates the human DNA mismatch repair system

AJP Cell Physiology ◽

10.1152/ajpcell.00422.2001 ◽

2002 ◽

Vol 283 (1) ◽

pp. C148-C154 ◽

Cited By ~ 168

Author(s):

Christina L. Chang ◽

Giancarlo Marra ◽

Dharam P. Chauhan ◽

Hannah T. Ha ◽

Dong K. Chang ◽

...

Keyword(s):

Oxidative Stress ◽

Mismatch Repair ◽

Chronic Inflammation ◽

Dna Mismatch Repair ◽

Repair System ◽

Dna Microsatellites ◽

Single Base ◽

Dna Mismatch ◽

Human Dna ◽

Dna Mismatch Repair System

In the human DNA mismatch repair (MMR) system, hMSH2 forms the hMutSα and hMutSβ complexes with hMSH6 and hMSH3, respectively, whereas hMLH1 and hPMS2 form the hMutLα heterodimer. These complexes, together with other components in the MMR system, correct single-base mismatches and small insertion/deletion loops that occur during DNA replication. Microsatellite instability (MSI) occurs when the loops in DNA microsatellites are not corrected because of a malfunctioning MMR system. Low-frequency MSI (MSI-L) is seen in some chronically inflamed tissues in the absence of genetic inactivation of the MMR system. We hypothesize that oxidative stress associated with chronic inflammation might damage protein components of the MMR system, leading to its functional inactivation. In this study, we demonstrate that noncytotoxic levels of H2O2 inactivate both single-base mismatch and loop repair activities of the MMR system in a dose-dependent fashion. On the basis of in vitro complementation assays using recombinant MMR proteins, we show that this inactivation is most likely due to oxidative damage to hMutSα, hMutSβ, and hMutLα protein complexes. We speculate that inactivation of the MMR function in response to oxidative stress may be responsible for the MSI-L seen in nonneoplastic and cancer tissues associated with chronic inflammation.

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Synergic Crosstalk between Inflammation, Oxidative Stress, and Genomic Alterations in BCR–ABL-Negative Myeloproliferative Neoplasm

Antioxidants ◽

10.3390/antiox9111037 ◽

2020 ◽

Vol 9 (11) ◽

pp. 1037

Author(s):

Alessandro Allegra ◽

Giovanni Pioggia ◽

Alessandro Tonacci ◽

Marco Casciaro ◽

Caterina Musolino ◽

...

Keyword(s):

Oxidative Stress ◽

Stem Cell ◽

Chronic Inflammation ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Tumor Stage ◽

Driver Mutations ◽

Hematopoietic Stem ◽

Chronic Myeloproliferative Neoplasms ◽

Inflammatory State

Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have recently been revealed to be related to chronic inflammation, oxidative stress, and the accumulation of reactive oxygen species. It has been proposed that MPNs represent a human inflammation model for tumor advancement, in which long-lasting inflammation serves as the driving element from early tumor stage (over polycythemia vera) to the later myelofibrotic cancer stage. It has been theorized that the starting event for acquired stem cell alteration may occur after a chronic inflammation stimulus with consequent myelopoietic drive, producing a genetic stem cell insult. When this occurs, the clone itself constantly produces inflammatory components in the bone marrow; these elements further cause clonal expansion. In BCR–ABL1-negative MPNs, the driver mutations include JAK 2, MPL, and CALR. Transcriptomic studies of hematopoietic stem cells from subjects with driver mutations have demonstrated the upregulation of inflammation-related genes capable of provoking the development of an inflammatory state. The possibility of acting on the inflammatory state as a therapeutic approach in MPNs appears promising, in which an intervention operating on the pathways that control the synthesis of cytokines and oxidative stress could be effective in reducing the possibility of leukemic progression and onset of complications.

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Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: Health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic acids

Food Chemistry ◽

10.1016/j.foodchem.2019.03.127 ◽

2019 ◽

Vol 290 ◽

pp. 114-124 ◽

Cited By ~ 6

Author(s):

Wageh Sobhy Darwish ◽

Hitoshi Chiba ◽

Waleed Rizk El-Ghareeb ◽

Abdelazim Elsayed Elhelaly ◽

Shu-Ping Hui

Keyword(s):

Oxidative Stress ◽

Risk Assessment ◽

Polycyclic Aromatic Hydrocarbon ◽

Human Colon ◽

Hydrocarbon Content ◽

Heat Treated ◽

Polycyclic Aromatic ◽

Ascorbic Acids ◽

And Oxidative Stress

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Major and Minor Risk Factors for Cardiovascular Disease in Continuous Ambulatory Peritoneal Dialysis Patients

Peritoneal Dialysis International ◽

10.1177/089686089901902s21 ◽

1999 ◽

Vol 19 (2_suppl) ◽

pp. 133-137 ◽

Cited By ~ 5

Author(s):

Sarah Prichard

Keyword(s):

Oxidative Stress ◽

Risk Factors ◽

Cardiovascular Disease ◽

Peritoneal Dialysis ◽

Chronic Inflammation ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Treatment Strategies ◽

Dialysis Patients ◽

Lipid Abnormalities ◽

Conventional Risk Factors

Uremia in general and peritoneal dialysis in particular bring with them risk factors for the development of cardiovascular disease. These factors include multiple lipid abnormalities, hyperhomocysteinemia, abdominal obesity, chronic inflammation, hypoalbuminemia, oxidative stress, and AGE formation. When these are combined with conventional risk factors, one can appreciate why the incidence of cardiovascular disease is so high in peritoneal dialysis patients. Treatment strategies should address each of these risks appropriately.

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