Melatonin Modulates Regulation of NOX2 and NOX4 Following Irradiation in the Lung

2019 ◽  
Vol 14 (3) ◽  
pp. 224-231 ◽  
Author(s):  
Masoud Najafi ◽  
Alireza Shirazi ◽  
Elahe Motevaseli ◽  
Ghazale Geraily ◽  
Peyman Amini ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Continuous Production ◽  
Male Rats ◽  
Whole Body ◽  
Oxygen Species ◽  
Local Irradiation ◽  
Nadph Oxidases ◽  
Melatonin Treatment ◽  
Protein Levels ◽  
Radiation Induced

Background: Exposure to ionizing radiation may lead to chronic upregulation of inflammatory mediators and pro-oxidant enzymes, which give rise to continuous production of reactive oxygen species (ROS). NADPH oxidases are among the most important ROS producing enzymes. Their upregulation is associated with DNA damage and genomic instability. In the present study, we sought to determine the expressions of NADPH oxidases; NOX2 and NOX4, in rat’s lung following whole body or pelvis irradiation. In addition, we evaluated the protective effect of melatonin on the expressions of NOX2 and NOX4, as well as oxidative DNA injury. Materials and Methods: 35 male rats were divided into 7 groups, G1: control; G2: melatonin (100 mg/kg) treatment; G3: whole body irradiation (2 Gy); G4: melatonin plus whole body irradiation; G5: local irradiation to pelvis area; G6: melatonin treatment plus 2 Gy gamma rays to pelvis area; G7: scatter group. All the rats were sacrificed after 24 h. afterwards, the expressions of TGFβR1, Smad2, NF- κB, NOX2 and NOX4 were detected using real-time PCR. Also, the level of 8-OHdG was detected by ELISA, and NOX2 and NOX4 protein levels were detected by western blot. Results: Whole body irradiation led to the upregulation of all genes, while local pelvis irradiation caused upregulation of TGFβR1, NF-κB, NOX2 and NOX4, as well as protein levels of NOX2 and NOX4. Treatment with melatonin reduced the expressions of these genes and also alleviated oxidative injury in both targeted and non-targeted lung tissues. Results also showed no significant reduction for NOX2 and NOX4 in bystander tissues following melatonin treatment. Conclusion: It is possible that upregulation of NOX2 and NOX4 is involved in radiation-induced targeted and non-targeted lung injury. Melatonin may reduce oxidative stress following upregulation of these enzymes in directly irradiated lung tissues but not for bystander.

Evaluating Radioprotection of Rat’s Jejunum by a Combination of Melatonin and Metformin

2020 ◽  
Vol 17 (4) ◽  
pp. 479-484
Author(s):  
Nasim Ahmadi Azar ◽  
Abdolreza Javadi ◽  
Masoud Najafi ◽  
Alireza Shirazi ◽  
Elham Tajabadi ◽  
...  
Keyword(s):  
Gamma Rays ◽  
Male Rats ◽  
Whole Body ◽  
High Dose ◽  
Radiation Toxicity ◽  
Single Administration ◽  
Severe Injuries ◽  
Dna Damage Responses ◽  
Radiation Induced

Background: ejunum is one of the most radiosensitive parts of the gastrointestinal system. This is the main issue, leading to several side effects to patients with abdominal cancers, in addition to affecting their quality of life. Epithelial layer and clonogenic cells in the jejunum are the most sensitive parts of the intestine, while damage to vascular may lead to chronic inflammation and bleeding. Both melatonin and metformin have shown abilities to attenuate radiation toxicities through the modulation of DNA damage responses, neutralization of free radicals and alleviation of inflammation. In this study, we aimed to evaluate the possible radioprotective effects of melatonin and metformin when administered either alone or as a combination, in rat’s jejunum against a high dose of radiation. Methods: 40 male rats were divided into 8 groups as G1: control; G2: metformin; G3: melatonin; G4: melatonin + metformin; G5: radiation; G6: radiation + melatonin; G7: radiation + metformin; G8: metformin + melatonin + radiation. Rats were irradiated with 10 Gy gamma rays, while treatments were administered at 100 mg/kg. The ratio for melatonin and metformin was 1:1. 3.5 days after irradiation, all rats were sacrificed, followed by histopathological evaluation of the jejunum. Results: This study showed that whole body irradiation of rats led to severe injuries to the epithelial and vascular of jejunum. A single administration of either melatonin or metformin was unable to mitigate radiation toxicity. However, administering the combination of melatonin and metformin could mildly mitigate radiation-induced jejunum injury. Conclusion: From the results of this study, we suggest that the combination of melatonin and metformin has superior radioprotective effect for jejunum compared with the single administration of these drugs.

Radioprotective effect of Curcuma longa extract on γ-irradiation-induced oxidative stress in rats

2012 ◽  
Vol 90 (4) ◽  
pp. 415-423 ◽  
Author(s):  
Ahmed S. Nada ◽  
Asrar M. Hawas ◽  
Nour El-Din Amin ◽  
Magdy M. Elnashar ◽  
Zakaria Y. Abd Elmageed
Keyword(s):  
Oxidative Stress ◽  
Aqueous Extract ◽  
Antioxidant Status ◽  
Curcuma Longa ◽  
Radioprotective Effect ◽  
Male Rats ◽  
Sublethal Dose ◽  
Γ Irradiation ◽  
Protein Levels ◽  
Radiation Induced

This study was conducted to evaluate the modulatory effect of aqueous extract of Curcuma longa (L.) against γ-irradiation (GR), which induces biochemical disorders in male rats. The sublethal dose of GR was determined in primary hepatocytes. Also, the effect of C. longa extract was examined for its activity against GR. In rats, C. longa extract was administered daily (200 mg/kg body mass) for 21 days before, and 7 days after GR exposure (6.5 Gy). The lipid profile and antioxidant status, as well as levels of transaminases, interleukin-6 (IL-6), and tumour necrosis factor α (TNFα) were assessed. The results showed that in hepatocytes, the aqueous extract exhibited radioprotective activity against exposure to GR. Exposure of untreated rats to GR resulted in transaminase disorders, lipid abnormalities, elevation of lipid peroxidation, trace element alterations, release of IL-6 and TNF, and decrease in glutathione and protein level of superoxide dismutase-1 (SOD-1) and peroxiredoxin-1 (PRDX-1). However, treatment of rats with this extract before and after GR exposure improved antioxidant status and minimized the radiation-induced increase in inflammatory cytokines. Changes occurred in the tissue levels of trace elements, and the protein levels of SOD-1 and PRDX-1 were also modulated by C. longa extract. Overall, C. longa exerted a beneficial radioprotective effect against radiation-induced oxidative stress in male rats by alleviating pathological disorders and modulating antioxidant enzymes.

scholarly journals Phenotypic and Functional Characteristics of Exosomes Derived from Irradiated Mouse Organs and Their Role in the Mechanisms Driving Non-Targeted Effects

2020 ◽  
Vol 21 (21) ◽  
pp. 8389
Author(s):  
Seda Tuncay Cagatay ◽  
Ammar Mayah ◽  
Mariateresa Mancuso ◽  
Paola Giardullo ◽  
Simonetta Pazzaglia ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Mouse Embryonic Fibroblast ◽  
Whole Body ◽  
Recipient Mouse ◽  
Oxygen Species ◽  
Cellular Viability ◽  
Radiation Induced ◽  
Partial Body ◽  
Embryonic Fibroblast

Molecular communication between irradiated and unirradiated neighbouring cells initiates radiation-induced bystander effects (RIBE) and out-of-field (abscopal) effects which are both an example of the non-targeted effects (NTE) of ionising radiation (IR). Exosomes are small membrane vesicles of endosomal origin and newly identified mediators of NTE. Although exosome-mediated changes are well documented in radiation therapy and oncology, there is a lack of knowledge regarding the role of exosomes derived from inside and outside the radiation field in the early and delayed induction of NTE following IR. Therefore, here we investigated the changes in exosome profile and the role of exosomes as possible molecular signalling mediators of radiation damage. Exosomes derived from organs of whole body irradiated (WBI) or partial body irradiated (PBI) mice after 24 h and 15 days post-irradiation were transferred to recipient mouse embryonic fibroblast (MEF) cells and changes in cellular viability, DNA damage and calcium, reactive oxygen species and nitric oxide signalling were evaluated compared to that of MEF cells treated with exosomes derived from unirradiated mice. Taken together, our results show that whole and partial-body irradiation increases the number of exosomes, instigating changes in exosome-treated MEF cells, depending on the source organ and time after exposure.

Mitigation of Radiation-Induced Gastrointestinal System Injury by Melatonin: A Histopathological Study

2020 ◽  
Vol 12 (1) ◽  
pp. 72-79
Author(s):  
Hossein Sadeghi ◽  
Hamed Bagheri ◽  
Babak Shekarchi ◽  
Abdolreza Javadi ◽  
Masoud Najafi
Keyword(s):  
Gamma Ray ◽  
Radiation Treatment ◽  
Cell Damage ◽  
Gastrointestinal System ◽  
Whole Body ◽  
Histopathological Study ◽  
Radiation Toxicity ◽  
Melatonin Treatment ◽  
Gastrointestinal Injury ◽  
Radiation Induced

Aims : The current study aimed to investigate the potential role of melatonin in the mitigation of radiation-induced gastrointestinal injury. Background: Organs of the gastrointestinal system such as the intestines, colon, duodenum, ileum etc. are sensitive to ionizing radiation. Mitigation of radiation-induced gastrointestinal injury is an interesting topic in radiobiology and a life-saving approach for exposed persons after a radiation event or improving the quality of life of radiotherapy patients. Methods: 40 male mice were randomly assigned into four groups namely G1: control, G2: melatonin treatment, G3: whole-body irradiation, and G4: melatonin treatment after whole-body irradiation. A cobalt-60 gamma-ray source was used to deliver 7 Gy to the whole body. 100 mg/kg melatonin was administered orally 24 h after irradiation and continued for 5 days. Thirty days after irradiation, histopathological evaluations were performed. Results: The whole-body irradiation led to remarkable inflammation, villi shortening, apoptosis and damage to goblet cells of the small intestine. Furthermore, moderate to severe inflammation, apoptosis, congestion, crypt injury and goblet cell damage were reported for the colon. Treatment with melatonin after whole-body irradiation led to significant mitigation of radiation toxicity in both small and large intestines. Conclusion: Melatonin could mitigate intestinal injury following whole-body exposure to radiation. Treatment with melatonin after an accidental exposure to radiation may increase survival via mitigation of damages to radiosensitive organs, including the gastrointestinal system.

scholarly journals Crosstalk Between SMPDL3b and NADPH Oxidases Mediates Radiation-Induced Damage of Renal Podocytes

2021 ◽  
Vol 8 ◽  
Author(s):  
Patrick Azzam ◽  
Marina Francis ◽  
Tarek Youssef ◽  
Manal Mroueh ◽  
Alaa Abou Daher ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Radiation Injury ◽  
Oxygen Species ◽  
Collateral Damage ◽  
Wild Type ◽  
Nadph Oxidases ◽  
Radiation Induced ◽  
And Oxidative Stress ◽  
Glomerular Morphology

Patients undergoing radiotherapy (RT) for various tumors localized in the abdomen or pelvis often suffer from radiation nephrotoxicity as collateral damage. Renal podocytes are vulnerable targets for ionizing radiation and contribute to radiation-induced nephropathies. Our prior work previously highlighted the importance of the lipid-modifying enzyme sphingomyelinase acid phosphodiesterase like 3b (SMPDL3b) in modulating the radiation response in podocytes and glomerular endothelial cells. Hereby, we investigated the interplay between SMPDL3b and oxidative stress in mediating radiation injury in podocytes. We demonstrated that the overexpression of SMPDL3b in cultured podocytes (OE) reduced superoxide anion generation and NADPH oxidase activity compared to wild-type cells (WT) post-irradiation. Furthermore, OE podocytes showed downregulated levels of NOX1 and NOX4 after RT. On the other hand, treatment with the NOX inhibitor GKT improved WTs' survival post-RT and restored SMPDL3b to basal levels. in vivo, the administration of GKT restored glomerular morphology and decreased proteinuria in 26-weeks irradiated mice. Taken together, these results suggest a novel role for NOX-derived reactive oxygen species (ROS) upstream of SMPDL3b in modulating the response of renal podocytes to radiation.

Studying the antioxidant role of mushroom against hazards of gamma radiation exposure in male rats

2018 ◽  
Author(s):  
R. G. Hamza ◽  
A.N. El Shahat ◽  
M.N. Al-seeni
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Male Rats ◽  
Whole Body ◽  
Antioxidant Enzyme Activities ◽  
Lipid Peroxidation Product ◽  
Radiation Induced ◽  
Peroxidation Product ◽  
Histological Architecture

This study aimed to investigate the antioxidant role of dried mushroom (DM) against hazards of gamma-irradiation in male rats. In this study, exposure of rats to whole body g-radiation (6 Gy) resulted in hepatic oxidative stress (a significant increase in lipid peroxidation concomitant with a significant decrease in glutathione content and antioxidant enzyme activities); increase liver function enzymes and histopathological disorders. Treatment of irradiated rats with 10% DM significantly improved radiation-induced injury as indicated by the reduction of the indices of liver damage, lipid peroxidation product, the elevation of antioxidants and the attenuation of the tissues histological architecture. These results suggest that oyster mushroom can improve the antioxidant status and minimize the occurrence of oxidative stress- associated disorders.

scholarly journals The roles of NADPH oxidases during adult zebrafish fin regeneration

2021 ◽  
Author(s):  
Kunal Chopra ◽  
Milda Folkmanaite ◽  
Liam Stockdale ◽  
Vishali Shathish ◽  
Shoko Ishibashi ◽  
...  
Keyword(s):  
Transgenic Line ◽  
The Other ◽  
Whole Body ◽  
Ros Production ◽  
Oxygen Species ◽  
Adult Zebrafish ◽  
Nadph Oxidases ◽  
Fin Regeneration ◽  
Organ Regeneration ◽  
Mutant Lines

Sustained elevated levels of reactive oxygen species (ROS) have been shown to be essential for whole body, appendage and organ regeneration in various organisms, including planarians, Hydra, zebrafish, axolotl, Xenopus, geckos and mice. In the majority of cases these roles have been shown via the use of NADPH oxidase pharmacological inhibitors, which generally target all NAPDH oxidases (NOXes). To identify the specific NOX or NOXes essential for ROS production during adult fin regeneration in zebrafish, we generated nox mutants for duox, nox5 and cyba (a key subunit of NOXes 1-4). We also crossed these mutant lines to a transgenic line ubiquitously expressing HyPer, which permits the measurement of ROS levels in adult zebrafish fins. Using this approach, we found that homozygous duox mutants have significantly attenuated ROS levels following fin amputation, and this correlated with a significantly diminished rate of fin regeneration. While the other nox homozygous mutants (nox5 and cyba) showed less of an effect on ROS levels or adult fin regeneration, duox/cyba double mutants showed a more diminished rate of fin regeneration than duox mutants alone, suggesting that Nox1-4 do play a role during regeneration, but one that is secondary to that of Duox. This work also serendipitously found that ROS levels in amputated adult zebrafish fins oscillate during the day with a circadian rhythm.

Radioimmunotherapy of Xenografts of Human Pancreatic Carcinomas - Intravenous and Intratumoral Application of 131l-Labelled Monoclonal Antibodies

1986 ◽  
Vol 25 (06) ◽  
pp. 235-238 ◽  
Author(s):  
S. Lander ◽  
M. Bahlo ◽  
R. Montz ◽  
R. Klapdor
Keyword(s):  
Irradiation Dose ◽  
Tumor Regression ◽  
Whole Body ◽  
Inhibit Tumor Growth ◽  
Local Irradiation ◽  
Clinical Value ◽  
Direct Radiation ◽  
Intravenous Injections ◽  
Induce Tumor Regression ◽  
High Doses

The effects of radioimmunotherapy were tested in xenografts of 2 different human pancreatic carcinomas comparing the intravenous and intratumoral application. On principle, intravenous injections of high doses of 131l-anti- Ca 19-9 or -BW 494/32 may inhibit tumor growth. In view of the low direct radiation dose (360-2100 rad), however, other factors than direct toxic effects have to be discussed, e. g. systemic effects due to the high whole-body irradiation. Intratumoral application, however, may induce tumor regression or growth inhibition due to the high local irradiation dose. Consequently, this treatment modality might be of clinical value at least in some patients.

Mitigation of Radiation-induced Gastrointestinal System Injury using Resveratrol or Alpha-lipoic Acid: A Pilot Histopathological Study

2020 ◽  
Vol 19 (4) ◽  
pp. 413-424
Author(s):  
Bagher Farhood ◽  
Gholamreza Hassanzadeh ◽  
Peyman Amini ◽  
Dheyauldeen Shabeeb ◽  
Ahmed Eleojo Musa ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Gamma Ray ◽  
Morphological Changes ◽  
Gastrointestinal System ◽  
Alpha Tocopherol ◽  
Whole Body ◽  
Histopathological Study ◽  
Alpha Lipoic Acid ◽  
Pilot Investigation ◽  
Radiation Induced

Aim: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. Background: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. Objective: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. Methods: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. Results and Conclusion: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. Conclusion: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

scholarly journals Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark

Diabetologia ◽  
2021 ◽  
Author(s):  
Juliana de Almeida-Faria ◽  
Daniella E. Duque-Guimarães ◽  
Thomas P. Ong ◽  
Lucas C. Pantaleão ◽  
Asha A. Carpenter ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Glucose Tolerance ◽  
Er Stress ◽  
Maternal Obesity ◽  
Luciferase Assay ◽  
Whole Body ◽  
Mrna Levels ◽  
Protein Levels ◽  
Novel Targets

Abstract Aims/hypothesis Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. Methods miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic–hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. Results The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. Conclusions/interpretation Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target. Graphical abstract

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