Hepatic epigenomic changes associated with chronic oxidative stress in a mouse model of glutathione deficiency

Background:The formation of hyperphosphorylated tau and the production of β-amyloid are thought to be critical steps contributing to the pathological mechanisms in Alzheimer’s disease (AD). However, there has been a long-lasting debate over their importance in the onset of AD. Recent studies have demonstrated that axonopathy is considered as an early neuropathological change of AD. However, the exact relationship between the development of axonopathy and the classic neuropathological changes such as senile plaques (SPs) and neurofibrillary tangles (NFTs) is unclear.Objective:The aim of this study was to investigate whether the formation of SPs and NFTs is associated with the development of axonal leakage.Method and Results:Here we show that the formation and development of axonal leakage - a novel axonopathy is an age-dependent process, accompanied by swellings of axons and varicosities and associated with chronic oxidative stress induced by thiamine deficient (TD) diet in Kunming mice. In an APP/PS1 transgenic mouse model of AD, axonal leakage appears at 3 months, becomes more obvious at 6 months and severe, beyond 1 year. We also show that slight axonal leakage is related to the formation of hyperphosphorylated tau, but not plaques, and that only severe axonal leakage accompanied by the extensive swollen axons and varicosities, and overproduction of β-amyloid leads to the formation of SPs and hyperphosphorylated tau.Conclusion:These data provide an explanation of the common origin and development of SPs and NFTs, and suggest that axonal leakage might be a key event in the development of the neuropathological processes in AD.

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Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency

The Science of The Total Environment ◽

10.1016/j.scitotenv.2021.150703 ◽

2021 ◽

pp. 150703

Author(s):

Ying Chen ◽

Yewei Wang ◽

Georgia Charkoftaki ◽

David J. Orlicky ◽

Emily Davidson ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Liver Toxicity ◽

Glutathione Deficiency

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Lack of the P2X7 receptor protects against AMD-like defects and microparticle accumulation in a chronic oxidative stress-induced mouse model of AMD

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2016.10.140 ◽

2017 ◽

Vol 482 (1) ◽

pp. 81-86 ◽

Cited By ~ 5

Author(s):

Kyle A. Carver ◽

C.M. Lin ◽

Catherine Bowes Rickman ◽

Dongli Yang

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

P2x7 Receptor ◽

Chronic Oxidative Stress

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Faculty Opinions recommendation of Oxidative stress in skeletal muscle stimulates early expression of Rad in a mouse model of amyotrophic lateral sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.7576956.7874055 ◽

2011 ◽

Author(s):

Brett Adams ◽

Roger Bannister

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Amyotrophic Lateral Sclerosis ◽

Mouse Model ◽

Early Expression ◽

Lateral Sclerosis

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Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model

International Journal of Molecular Sciences ◽

10.3390/ijms22126603 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6603

Author(s):

Bushra Shal ◽

Adnan Khan ◽

Ashraf Ullah Khan ◽

Rahim Ullah ◽

Gowhar Ali ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Neuroprotective Effect ◽

Annexin V ◽

Memory Deficit ◽

Y Maze ◽

Spatial Memory Deficit ◽

Aβ Aggregation ◽

Ft Ir ◽

Reelin Signaling

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against H2O2-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1–42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.

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Increased Oxidative Stress in Acute Myeloid Leukemia Patients after Red Blood Cell Transfusion, but Not Platelet Transfusion, Results Mainly from the Oxidative/Nitrative Protein Damage: An Exploratory Study

Journal of Clinical Medicine ◽

10.3390/jcm10071349 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1349

Author(s):

Kamila Czubak-Prowizor ◽

Jacek Trelinski ◽

Paulina Stelmach ◽

Piotr Stelmach ◽

Agnieszka Madon ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Myeloid Leukemia ◽

Exploratory Study ◽

Myeloid Leukemia ◽

Thiobarbituric Acid ◽

Red Blood Cell Transfusion ◽

Packed Red Blood Cells ◽

Chronic Oxidative Stress ◽

Total Antioxidant ◽

Acute Myeloid

Chronic oxidative stress (OS) can be an important factor of acute myeloid leukemia (AML) progression; however, there are no data on the extent/consequence of OS after transfusion of packed red blood cells (pRBCs) and platelet concentrates (PCs), which are commonly used in the treatment of leukemia-associated anemia and thrombocytopenia. We aimed to investigate the effects of pRBC/PC transfusion on the OS markers, i.e., thiol and carbonyl (CO) groups, 3-nitrotyrosine (3-NT), thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGE), total antioxidant capacity (TAC), SOD, GST, and LDH, in the blood plasma of AML patients, before and 24 h post-transfusion. In this exploratory study, 52 patients were examined, of which 27 were transfused with pRBCs and 25 with PCs. Age-matched healthy subjects were also enrolled as controls. Our results showed the oxidation of thiols, increased 3-NT, AGE levels, and decreased TAC in AML groups versus controls. After pRBC transfusion, CO groups, AGE, and 3-NT significantly increased (by approximately 30, 23, and 35%; p < 0.05, p < 0.05, and p < 0.01, respectively) while thiols reduced (by 18%; p < 0.05). The PC transfusion resulted in the raise of TBARS and AGE (by 45%; p < 0.01 and 31%; p < 0.001), respectively). Other variables showed no significant post-transfusion changes. In conclusion, transfusion of both pRBCs and PCs was associated with an increased OS; however, transfusing the former may have more severe consequences, since it is associated with the irreversible oxidative/nitrative modifications of plasma proteins.

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Oxidative Stress and Mitochondrial Damage in Dry Age-Related Macular Degeneration Like NFE2L2/PGC-1α -/- Mouse Model Evoke Complement Component C5a Independent of C3

Biology ◽

10.3390/biology10070622 ◽

2021 ◽

Vol 10 (7) ◽

pp. 622

Author(s):

Iswariyaraja Sridevi Gurubaran ◽

Hanna Heloterä ◽

Stephen Marry ◽

Ali Koskela ◽

Juha M. T. Hyttinen ◽

...

Keyword(s):

Oxidative Stress ◽

Mouse Model ◽

Macular Degeneration ◽

Complement Component ◽

Factor H ◽

Age Related Macular Degeneration ◽

Related Factor ◽

Complement Factor ◽

Age Related ◽

Dry Amd

Aging-associated chronic oxidative stress and inflammation are known to be involved in various diseases, e.g., age-related macular degeneration (AMD). Previously, we reported the presence of dry AMD-like signs, such as elevated oxidative stress, dysfunctional mitophagy and the accumulation of detrimental oxidized materials in the retinal pigment epithelial (RPE) cells of nuclear factor erythroid 2-related factor 2, and a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (NFE2L2/PGC1α) double knockout (dKO) mouse model. Here, we investigated the dynamics of inflammatory markers in one-year-old NFE2L2/PGC1α dKO mice. Immunohistochemical analysis revealed an increase in levels of Toll-like receptors 3 and 9, while those of NOD-like receptor 3 were decreased in NFE2L2/PGC1α dKO retinal specimens as compared to wild type animals. Further analysis showed a trend towards an increase in complement component C5a independent of component C3, observed to be tightly regulated by complement factor H. Interestingly, we found that thrombin, a serine protease enzyme, was involved in enhancing the terminal pathway producing C5a, independent of C3. We also detected an increase in primary acute phase C-reactive protein and receptor for advanced glycation end products in NFE2L2/PGC1α dKO retina. Our main data show C5 and thrombin upregulation together with decreased C3 levels in this dry AMD-like model. In general, the retina strives to mount an orchestrated inflammatory response while attempting to maintain tissue homeostasis and resolve inflammation.

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