Mitigation of whole-body gamma radiation–induced damages by Clerodendron infortunatum in mammalian organisms

Abstract Several phytoceuticals and extracts of medicinal plants are reported to mitigate deleterious effects of ionizing radiation. The potential of hydro-alcoholic extract of Clerodendron infortunatum (CIE) for providing protection to mice exposed to gamma radiation was investigated. Oral administration of CIE bestowed a survival advantage to mice exposed to lethal doses of gamma radiation. Radiation-induced depletion of the total blood count and bone marrow cellularity were prevented by treatment with CIE. Damage to the cellular DNA (as was evident from the comet assay and the micronucleus index) was also found to be decreased upon CIE administration. Radiation-induced damages to intestinal crypt cells was also reduced by CIE. Studies on gene expression in intestinal cells revealed that there was a marked increase in the Bax/Bcl-2 ratio in mice exposed to whole-body 4 Gy gamma radiation, and that administration of CIE resulted in significant lowering of this ratio, suggestive of reduction of radiation-induced apoptosis. Also, in the intestinal tissue of irradiated animals, following CIE treatment, levels of expression of the DNA repair gene Atm were found to be elevated, and there was reduction in the expression of the inflammatory Cox-2 gene. Thus, our results suggest a beneficial use of Clerodendron infortunatum for mitigating radiation toxicity.

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Gamma radiation-induced apoptosis, G2 delay, and the risk of salivary and thyroid carcinomas?a preliminary report

Head & Neck ◽

10.1002/hed.20053 ◽

2004 ◽

Vol 26 (7) ◽

pp. 612-618 ◽

Cited By ~ 9

Author(s):

Rong Zheng ◽

Kristina R. Dahlstrom ◽

Qingyi Wei ◽

Erich M. Sturgis

Keyword(s):

Gamma Radiation ◽

Preliminary Report ◽

Thyroid Carcinomas ◽

Radiation Induced ◽

Induced Apoptosis ◽

G2 Delay

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Protection from Radiation-induced Damage in Rat’s Ileum and Colon by Combined Regimens of Melatonin and Metformin: A Histopathological Study

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry ◽

10.2174/1871523018666190718161928 ◽

2020 ◽

Vol 19 (2) ◽

pp. 180-189 ◽

Cited By ~ 2

Author(s):

Masoud Najafi ◽

Mohsen Cheki ◽

Gholamreza Hassanzadeh ◽

Peyman Amini ◽

Dheyauldeen Shabeeb ◽

...

Keyword(s):

Whole Body ◽

Gastrointestinal Disorders ◽

Histopathological Study ◽

Radiation Toxicity ◽

Pharmaceutical Treatment ◽

Tissue Samples ◽

Melatonin Administration ◽

Male Wistar Rats ◽

Radiation Induced ◽

High Doses

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

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141 Combined Treatment With PPAR Gamma Ligands and Gamma Radiation Induced Apoptosis Through Up-regulation of ROS-induced DNA Damage Signals in Human Lung Cancer Cells

European Journal of Cancer ◽

10.1016/s0959-8049(12)70841-9 ◽

2012 ◽

Vol 48 ◽

pp. S34

Author(s):

S. Hong ◽

E. Han ◽

E. Lee ◽

J. Park

Keyword(s):

Lung Cancer ◽

Dna Damage ◽

Gamma Radiation ◽

Human Lung ◽

Combined Treatment ◽

Ppar Gamma ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Radiation Induced ◽

Induced Apoptosis

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Geraniin down regulates gamma radiation-induced apoptosis by suppressing DNA damage

Food and Chemical Toxicology ◽

10.1016/j.fct.2013.03.022 ◽

2013 ◽

Vol 57 ◽

pp. 147-153 ◽

Cited By ~ 19

Author(s):

So Jin Bing ◽

Danbee Ha ◽

Min Ju Kim ◽

Eunjin Park ◽

Ginnae Ahn ◽

...

Keyword(s):

Dna Damage ◽

Gamma Radiation ◽

Radiation Induced ◽

Induced Apoptosis

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Effect of whole body hyperthermia (39°C, 1h) on radiation-induced apoptosis in Swiss mice

Journal of Thermal Biology ◽

10.1016/j.jtherbio.2003.08.007 ◽

2004 ◽

Vol 29 (1) ◽

pp. 3-8 ◽

Cited By ~ 5

Author(s):

A.K. Zaidi ◽

R.S. Bagewadikar ◽

M. Subramanian ◽

G.S. Kaklij ◽

M.S. Patil

Keyword(s):

Whole Body ◽

Swiss Mice ◽

Whole Body Hyperthermia ◽

Radiation Induced ◽

Induced Apoptosis

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Distinct vascular genomic response of proton and gamma radiation

10.1101/460766 ◽

2018 ◽

Author(s):

Ricciotti Emanuela ◽

Dimitra Sarantopoulou ◽

Gregory R. Grant ◽

Jenine K. Sanzari ◽

Gabriel S. Krigsfeld ◽

...

Keyword(s):

Gamma Radiation ◽

Dose Response ◽

Photon Radiation ◽

Radiation Response ◽

Whole Body ◽

Proton Radiation ◽

Vascular Effects ◽

Radiation Induced ◽

Total Body ◽

Genomic Response

AbstractPurpose. The cardiovascular biology of proton radiotherapy is not well understood. We aimed to compare the genomic dose-response to proton and gamma radiation of the mouse aorta to assess whether their vascular effects may diverge.Materials and methods.We performed comparative RNA sequencing of the aorta following (4 hrs) total-body proton and gamma irradiation (0.5 - 200 cGy whole body dose, 10 dose levels) of conscious mice. A trend analysis identified genes that showed a dose response.Results.While fewer genes were dose-responsive to proton than gamma radiation (29 vs. 194 genes;q-value ≤ 0.1), the magnitude of the effect was greater. Highly responsive genes were enriched for radiation response pathways (DNA damage, apoptosis, cellular stress and inflammation;p-value ≤ 0.01). Gamma, but not proton radiation induced additionally genes in vasculature specific pathways. Genes responsive to both radiation types showed almost perfectly superimposable dose-response relationships.Conclusions.Despite the activation of canonical radiation response pathways by both radiation types, we detected marked differences in the genomic response of the murine aorta. Models of cardiovascular risk based on photon radiation may not accurately predict the risk associated with proton radiation.

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

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190617153004 ◽

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.

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Temporal Gene Regulation During HIV-1 Infection of Human CD4+ T Cells

Genome Research ◽

10.1101/gr.180201 ◽

2001 ◽

Vol 11 (7) ◽

pp. 1198-1204

Author(s):

Jacques Corbeil ◽

Dennis Sheeter ◽

Davide Genini ◽

Steffney Rought ◽

Lorenzo Leoni ◽

...

Keyword(s):

T Cell ◽

Host Cell ◽

Genotoxic Stress ◽

Repair Gene ◽

Dna Repair Gene ◽

Its Gene ◽

Gene Transcripts ◽

Infected Cells ◽

Induced Apoptosis ◽

Hiv 1

CD4+ T-cell depletion is a characteristic of human immunodeficiency virus type 1 (HIV-1) infection. In this study, modulation of mRNA expression of 6800 genes was monitored simultaneously at eight time points in a CD4+ T-cell line (CEM-GFP) during HIV infection. The responses to infection included: (1) >30% decrease at 72 h after infection in overall host-cell production of monitored mRNA synthesis, with the replacement of host-cell mRNA by viral mRNA, (2) suppression of the expression of selected mitochondrial and DNA repair gene transcripts, (3) increased expression of the proapoptotic gene and its gene p53-induced product Bax, and (4) activation of caspases 2, 3, and 9. The intense HIV-1 transcription resulted in the repression of much cellular RNA expression and was associated with the induction of apoptosis of infected cells but not bystander cells. This choreographed host gene response indicated that the subversion of the cell transcriptional machinery for the purpose of HIV-1 replication is akin to genotoxic stress and represents a major factor leading to HIV-induced apoptosis.

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