Association Between DNA and RNA Oxidative Damage and Mortality of Patients with Traumatic Brain Injury

Lorente, Leonardo; Martı́n, Marı́a; González-Rivero, Agustín F.; Pérez-Cejas, Antonia; Abreu-González, Pedro; Ramos, Luís; Argueso, Mónica; Cáceres, Juan J.; Solé‐Violán, Jordi; Álvarez-Castillo, Andrea; Jiménez, Alejandro; Garcı́a-Marı́n, Vı́ctor

doi:10.1007/s12028-019-00800-w

Cited by 14 publications

(9 citation statements)

References 30 publications

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“…As in our previous studies, 8-oxo-G was used as a DNA damage marker [24,60,70,72,90], and TBI changes guanine to 8-oxo-G under oxidative stress and accumulates it [48,54]. From our results, Derinat suppressed DNA damage on both the 7 th and 14 th days (Figure 2).…”

Section: Discussionsupporting

confidence: 79%

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

et al. 2021

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Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury.

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Section: Discussionsupporting

confidence: 79%

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

et al. 2021

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“…In the blood plasma of patients with brain injury, a study in 2014 found that levels of cell free DNA correlated with severity of brain injury (mild vs. severe) (Shaked et al, 2014). Similarly, serum levels of 8-OHdG were found to correlate with mortality in patients with severe TBI, with patients who died from sustaining their injury having significantly elevated levels of this marker for oxidative DNA damage (Lorente et al, 2020).…”

Section: Dna Damage Biomarkers In Mtbi Patientsmentioning

confidence: 99%

Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives

Schwab

Leung

Hazrati

2021

Front. Aging Neurosci.

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Mild traumatic brain injury (mTBI) can lead to long-term neurological dysfunction and increase one's risk of neurodegenerative disease. Several repercussions of mTBI have been identified and well-studied, including neuroinflammation, gliosis, microgliosis, excitotoxicity, and proteinopathy – however the pathophysiological mechanisms activating these pathways after mTBI remains controversial and unclear. Emerging research suggests DNA damage-induced cellular senescence as a possible driver of mTBI-related sequalae. Cellular senescence is a state of chronic cell-cycle arrest and inflammation associated with physiological aging, mood disorders, dementia, and various neurodegenerative pathologies. This narrative review evaluates the existing studies which identify DNA damage or cellular senescence after TBI (including mild, moderate, and severe TBI) in both experimental animal models and human studies, and outlines how cellular senescence may functionally explain both the molecular and clinical manifestations of TBI. Studies on this subject clearly show accumulation of various forms of DNA damage (including oxidative damage, single-strand breaks, and double-strand breaks) and senescent cells after TBI, and indicate that cellular senescence may be an early event after TBI. Further studies are required to understand the role of sex, cell-type specific mechanisms, and temporal patterns, as senescence may be a pathway of interest to target for therapeutic purposes including prognosis and treatment.

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“…Simultaneous determination of 8-OHdG and 8-NG has been used to assess link between oxidative and/or nitrative damage and exposures to per- and polyfluoroalkyl substances [ 12 ], phthalates [ 14 ], or BPA [ 15 ]. Oxidized serum guanine (e.g., 8-OHdG, 8-HG, 8-HdG) has been associated with COVID-19 mortality [ 39 ], and elevated serum levels of 8-HG, 8-HdG, or 8-NdG have been linked to mortality associated with traumatic brain injury [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Oxidative damage to DNA by ROS can generate 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-HG), whereas that by RNS can yield 8-nitroguanine (8-NG). Reactions of ROS and RNS with RNA produce 8-hydroxyguanosine (8-HdG) and 8-nitroguanosine (8-NdG), respectively [ 12 , 14 , 18 ]. The biomarkers of oxidative damage to polyunsaturated fatty acids (PUFA) by ROS are malondialdehyde (MDA) and 4-hydroxynonenal (HNE) [ 19 , 20 ]; the oxidation of arachidonic acid (a fatty acid found in the liver, brain, and glands) can produce prostaglandin isomers, 8-isoprostaglandin F 2α (8-PGF 2α ), 11-β-prostaglandin F 2α (11-PGF 2α ), 15-prostaglandin F 2α (15-PGF 2α ), and 8-iso-15-prostaglandin F 2α (8,15-PGF 2α ) [ 21 ]; and uric acid oxidation yields allantoin (Alla) [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of 19 urinary biomarkers of oxidative stress, nitrative stress, metabolic disorders, and inflammation using liquid chromatography–tandem mass spectrometry

Martinez-Moral

2022

Anal Bioanal Chem

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Graphical abstract Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F 2α (8-PGF 2α ), 11-β-prostaglandin-F 2α (11-PGF 2α ), 15-prostaglandin-F 2α (15-PGF 2α ), 8-iso-15-prostaglandin-F 2α (8,15-PGF 2α ), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs) N ε -carboxymethyllysine (CML) and N ε -carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.

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Association Between DNA and RNA Oxidative Damage and Mortality of Patients with Traumatic Brain Injury

Cited by 14 publications

References 30 publications

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

Cellular Senescence in Traumatic Brain Injury: Evidence and Perspectives

Analysis of 19 urinary biomarkers of oxidative stress, nitrative stress, metabolic disorders, and inflammation using liquid chromatography–tandem mass spectrometry

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