scholarly journals Radioprotective effect of a combination of melatonin and metformin on mice spermatogenesis: A histological study

2020 ◽  
Author(s):  
Elham Tajabadi ◽  
Abdolreza Javadi ◽  
Nasim Ahmadi Azar ◽  
Masoud Najafi ◽  
Alireza Shirazi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Leydig Cells ◽  
Histological Study ◽  
Histological Evaluation ◽  
Radiation Toxicity ◽  
Single Administration ◽  
Single Drug ◽  
Dna Damage Responses ◽  
Key Words Radiation

Background: The spermatogenesis system includes highly radiosensitive cells. Hence, this system is a potential target for toxic effects of ionizing radiation during radiotherapy of abdomen and pelvis cancers, as well as after accidental radiation events. Accordingly, metformin and melatonin are two important radioprotectors that have shown an ability to prevent cell death through neutralization of free radicals and stimulating DNA damage responses. Objective: To evaluate the radioprotective effects of melatonin and metformin on mice spermatogenesis when administered alone or as a combination. Materials and Methods: In this histological Study, 40 (6-8 wk, 30 gr) NMRI mice were divided into 8 groups (n = 5/each) as control, metformin, melatonin, melatonin + metformin, radiation, radiation + melatonin, radiation + metformin, and radiation + melatonin + metformin. 37 days after the irradiation, the testicular tissues were collected for histological evaluation. Results: Single administration of melatonin could ameliorate effectively radiation toxicity in mice testis. Metformin showed radioprotective effects on some parameters such as the numbers of spermatogonia and mature sperms. Interestingly, the melatonin and metformin combination reversed the reduced number of sperms rather than single drug administration. Conclusion: The combination of melatonin with metformin can protect mice spermatogenesis against ionizing radiation more effectively compared to the single forms of these drugs. Key words: Radiation, Testis, Leydig cells, Melatonin, Metformin, Spermatogenesis.

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.

In VivoInteractions between Ionizing Radiation, Inflammation and Chemical Carcinogens Identified by Increased DNA Damage Responses

2012 ◽  
Vol 177 (5) ◽  
pp. 584-593 ◽  
Author(s):  
K. A. McAllister ◽  
S. A. Lorimore ◽  
E. G. Wright ◽  
P. J. Coates
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Chemical Carcinogens ◽  
Dna Damage Responses

scholarly journals Importance of CNOT8 Deadenylase Subunit in DNA Damage Responses Following Ionizing Radiation (IR)

2020 ◽  
Vol 9 (2) ◽  
pp. 163-170
Author(s):  
Samira Eskandarian ◽  
Roger Grand ◽  
Shiva Irani ◽  
Mohsen Saeedi ◽  
Reza Mirfakhraie ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Dna Damage Responses

Temporal Telomere and DNA Damage Responses in the Space Radiation Environment

2020 ◽  
Author(s):  
Jared J. Luxton ◽  
Miles J. McKenna ◽  
Lynn E. Taylor ◽  
Kerry A. George ◽  
Sara Zwart ◽  
...  
Keyword(s):  
Dna Damage ◽  
Space Radiation ◽  
Radiation Environment ◽  
Dna Damage Responses ◽  
Space Radiation Environment

A novel NGR-conjugated peptide targets DNA damage responses for radiosensitization

2015 ◽  
Vol 15 (6) ◽  
pp. 533-541 ◽  
Author(s):  
Jinlu Ma ◽  
Dan Zhang ◽  
Xia Ying ◽  
Ying Zhao ◽  
Chenchen He ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Responses

scholarly journals Exposure of the cytoplasm to low-dose X-rays modifies ataxia telangiectasia mutated-mediated DNA damage responses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Munetoshi Maeda ◽  
Masanori Tomita ◽  
Mika Maeda ◽  
Hideki Matsumoto ◽  
Noriko Usami ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Ataxia Telangiectasia ◽  
Kinase Inhibitor ◽  
Surrogate Marker ◽  
X Rays ◽  
Ataxia Telangiectasia Mutated ◽  
Whole Cell ◽  
X Ray ◽  
Dna Damage Responses

AbstractWe recently showed that when a low X-ray dose is used, cell death is enhanced in nucleus-irradiated compared with whole-cell-irradiated cells; however, the role of the cytoplasm remains unclear. Here, we show changes in the DNA damage responses with or without X-ray microbeam irradiation of the cytoplasm. Phosphorylated histone H2AX foci, a surrogate marker for DNA double-strand breaks, in V79 and WI-38 cells are not observed in nucleus irradiations at ≤ 2 Gy, whereas they are observed in whole-cell irradiations. Addition of an ataxia telangiectasia mutated (ATM) kinase inhibitor to whole-cell irradiations suppresses foci formation at ≤ 2 Gy. ABL1 and p73 expression is upregulated following nucleus irradiation, suggesting the induction of p73-dependent cell death. Furthermore, CDKN1A (p21) is upregulated following whole-cell irradiation, indicating the induction of cell cycle arrest. These data reveal that cytoplasmic radioresponses modify ATM-mediated DNA damage responses and determine the fate of cells irradiated at low doses.

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