scholarly journals Vitamin E Analogs as Radiation Response Modifiers

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Pankaj K. Singh ◽  
Sunil Krishnan
Keyword(s):  
Vitamin E ◽  
Ionizing Radiation ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Mechanisms Of Action ◽  
Life Threatening ◽  
Radiation Induced ◽  
Total Body ◽  
Effects Of Radiation ◽  
Effective Radiation

The potentially life-threatening effects of total body ionizing radiation exposure have been known for more than a century. Despite considerable advances in our understanding of the effects of radiation over the past six decades, efforts to identify effective radiation countermeasures for use in case of a radiological/nuclear emergency have been largely unsuccessful. Vitamin E is known to have antioxidant properties capable of scavenging free radicals, which have critical roles in radiation injuries. Tocopherols and tocotrienols, vitamin E analogs together known as tocols, have shown promise as radioprotectors. Although the pivotal mechanisms of action of tocols have long been thought to be their antioxidant properties and free radical scavenging activities, other alternative mechanisms have been proposed to drive their activity as radioprotectors. Here we provide a brief overview of the effects of ionizing radiation, the mechanistic mediators of radiation-induced damage, and the need for radiation countermeasures. We further outline the role for, efficacy of, and mechanisms of action of tocols as radioprotectors, and we compare and contrast their efficacy and mode of action with that of another well-studied chemical radioprotector, amifostine.

scholarly journals Modulation of Ionizing Radiation Induced Oxidative Imbalance by Semi-Fractionated Extract ofPiper betle: An In Vitro and In Vivo Assessment

2010 ◽  
Vol 3 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Savita Verma ◽  
Manju Lata Gupta ◽  
Ajaswrata Dutta ◽  
Sanghmitra Sankhwar ◽  
Sandeep Kumar Shukla ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Free Radical ◽  
Ionizing Radiation ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Antioxidant Potential ◽  
Normal Tissues ◽  
Radiation Induced

The study was planned to evaluate modulatory effect of aqueous extract ofPiper betleleaf (PBL) on ionizing radiation mediated oxidative stress leading to normal tissues damage during radiotherapy and other radiation exposures. The total polyphenols and flavonoids known as free radical scavenger (chelators) were measured in the extract. To ascertain antioxidant potential of PBL extract, we studied free radical scavenging, metal chelation, reducing power, lipid peroxidation inhibition and ferric reducing antioxidant properties (FRAP ) using in vitro assays. Mice were exposed to varied radiation doses administered with the same extract prior to irradiation to confirm its oxidative stress minimizing efficacy by evaluating ferric reducing ability of plasma, reduced glutathione, lipid peroxidation and micro-nuclei frequency. PBL extract was effective in scavenging DPPH (up to 92% at 100 µg/ml) and superoxide radicals (up to 95% at 80 µg/ml), chelated metal ions (up to 83% at 50 µg/ml) and inhibited lipid peroxidation (up to 45.65% at 500 µg/ml) in a dose dependant manner using in vitro model. Oral administration of PBL extract (225 mg/kg body weight) 1 hr before irradiation in mice significantly enhanced (p < 0.01) radiation abated antioxidant potential of plasma and GSH level in all the observed organs. The treatment with extract effectively lowered the radiation induced lipid peroxidation at 24 hrs in all the selected organs with maximum inhibition in thymus (p < 0.01). After 48 hrs, lipid peroxidation was maximally inhibited in the group treated with the extract. Frequency of radiation induced micronucleated cells declined significantly (34.78%, p < 0.01) at 24 hrs post-irradiation interval by PBL extract administration. The results suggest that PBL extract has high antioxidant potential and relatively non-toxic and thus could be assertively used to mitigate radiotherapy inflicted normal tissues damage and also injuries caused by moderate doses of radiation during unplanned exposures.

Ionizing radiation stimulates muscarinic regulation of rat intestinal mucosal function

1998 ◽  
Vol 275 (6) ◽  
pp. G1333-G1340 ◽  
Author(s):  
F. Lebrun ◽  
A. Francois ◽  
M. Vergnet ◽  
L. Lebaron-Jacobs ◽  
P. Gourmelon ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Enzyme Activities ◽  
Plasma Membranes ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Marker Enzyme ◽  
Γ Irradiation ◽  
Ussing Chambers ◽  
Radiation Induced ◽  
Total Body

The aim of this study was to determine whether ionizing radiation modifies muscarinic regulation of intestinal mucosal function. Rats exposed to total body 8-Gy γ-irradiation or sham irradiated were studied up to 21 days after irradiation. Basal and carbachol-stimulated short-circuit current ( I sc) and transepithelial conductance ( G t) of stripped ileum were determined in Ussing chambers. Muscarinic receptor characteristics using the muscarinic antagonist [3H]quinuclidinyl benzilate and three unlabeled antagonists were measured in small intestinal plasma membranes together with two marker enzyme activities (sucrase, Na+-K+-ATPase). Enzyme activities were decreased 4 days after irradiation ( day 4). Basal electrical parameters were unchanged. Maximal carbachol-induced changes in I sc and G t were increased at day 4 (maximal Δ I sc = 195.8 ± 14.7 μA/cm2, n = 19, vs. 115.4 ± 8.2 μA/cm2, n = 63, for control rats) and unchanged at day 7. Dissociation constant was decreased at day 4 (0.73 ± 0.29 nM, n = 10, vs. 2.14 ± 0.39 nM, n = 13, for control rats) but unchanged at day 7, without change in binding site number. Thus total body irradiation induces a temporary stimulation of cholinergic regulation of mucosal intestinal function that may result in radiation-induced diarrhea.

scholarly journals Pegylated G-CSF Inhibits Blood Cell Depletion, Increases Platelets, Blocks Splenomegaly, and Improves Survival after Whole-Body Ionizing Irradiation but Not after Irradiation Combined with Burn

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Juliann G. Kiang ◽  
Min Zhai ◽  
Pei-Jyun Liao ◽  
David L. Bolduc ◽  
Thomas B. Elliott ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Marrow Cell ◽  
Total Body Surface Area ◽  
Body Weight Loss ◽  
Cell Depletion ◽  
Photon Radiation ◽  
Whole Body ◽  
Life Threatening ◽  
Radiation Induced ◽  
Total Body

Exposure to ionizing radiation alone (radiation injury, RI) or combined with traumatic tissue injury (radiation combined injury, CI) is a crucial life-threatening factor in nuclear and radiological accidents. As demonstrated in animal models, CI results in greater mortality than RI. In our laboratory, we found that B6D2F1/J female mice exposed to60Co-γ-photon radiation followed by 15% total-body-surface-area skin burns experienced an increment of 18% higher mortality over a 30-day observation period compared to irradiation alone; that was accompanied by severe cytopenia, thrombopenia, erythropenia, and anemia. At the 30th day after injury, neutrophils, lymphocytes, and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were similar to basal levels. Comparing CI and RI mice, only RI induced splenomegaly. Both RI and CI resulted in bone marrow cell depletion. It was observed that only the RI mice treated with pegylated G-CSF after RI resulted in 100% survival over the 30-day period, and pegylated G-CSF mitigated RI-induced body-weight loss and depletion of WBC and platelets. Peg-G-CSF treatment sustained RBC balance, hemoglobin levels, and hematocrits and inhibited splenomegaly after RI. The results suggest that pegylated G-CSF effectively sustained animal survival by mitigating radiation-induced cytopenia, thrombopenia, erythropenia, and anemia.

scholarly journals Protective Effect of Houttuynia cordata Extract on Bleomycin-Induced Pulmonary Fibrosis in Rats

2007 ◽  
Vol 35 (03) ◽  
pp. 465-475 ◽  
Author(s):  
Lean-Teik Ng ◽  
Feng-Lin Yen ◽  
Chia-Wen Liao ◽  
Chun-Ching Lin
Keyword(s):  
Vitamin E ◽  
Pulmonary Fibrosis ◽  
Protective Effect ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Radical Scavenging ◽  
Liver Homogenate ◽  
Lavage Fluid ◽  
Model Systems ◽  
Houttuynia Cordata

The present study aimed to examine the antioxidant properties of Houttuynia cordata (HC) and its protective effect on bleomycin-induced pulmonary fibrosis in rats. Results showed that aqueous extract of HC exhibited a different magnitude of antioxidant activities in all model systems tested. Although HC showed weaker free radical scavenging and xanthine oxidase inhibitory activity than vitamin E, its anti-lipid peroxidation activity in rat liver homogenate was close to that of vitamin E. In animal studies, HC significantly decreased the levels of superoxide dismutase, malondialdehyde, hydroxyproline, interferon-γ, and tumor necrosis factor-α. However, an increase in the concentration of catalase was noted in the bronchoalveolar lavage fluid. HC also remarkably improved the morphological appearance of the lung of bleomycin-treated rats. These results suggest that HC possesses a protective effect against bleomycin-induced pulmonary fibrosis. Interestingly, this protective effect was more pronounced than that of vitamin E. In conclusion, the protective effect of HC on pulmonary fibrosis could be partly associated with the reduction of oxidative damage caused by bleomycin.

Role of Pentoxifylline and Vitamin E in Attenuation of Radiation-Induced Fibrosis

2005 ◽  
Vol 39 (3) ◽  
pp. 516-522 ◽  
Author(s):  
Teresa B Chiao ◽  
Audrey J Lee
Keyword(s):  
Nervous System ◽  
Vitamin E ◽  
Radiation Injury ◽  
Soft Tissues ◽  
Antioxidant Properties ◽  
Data Sources ◽  
Data Synthesis ◽  
Modest Improvement ◽  
Radiation Induced

OBJECTIVE: To evaluate the use of pentoxifylline and vitamin E as monotherapy and in combination for the treatment of radiation-induced fibrosis (RIF). DATA SOURCES: Literature retrieval was performed through MEDLINE (1966–March 2004) using the terms vitamin E, α-tocopherol, pentoxifylline, radiation-induced fibrosis, and radiation injury. DATA SYNTHESIS: Few treatments exist for managing RIF of soft tissues. Due to its antioxidant properties, vitamin E may reduce the oxidative damage induced by radiation. The precise mechanism of action for pentoxifylline in management of RIF remains unclear. Uncontrolled studies evaluating vitamin E or pentoxifylline as monotherapy in RIF have shown modest improvement in clinical regression of fibrosis. However, controlled data are needed to verify these benefits. Studies involving pentoxifylline plus vitamin E demonstrated regression in RIF. The combination was more effective than placebo and may be superior to monotherapy with either agent. Adverse effects were rarely reported in the studies and consisted mainly of gastrointestinal and nervous system effects. CONCLUSIONS: Overall, pentoxifylline is well tolerated and is one of the few commercially available drugs with clinical data for management of RIF. Despite a lack of large, well-designed clinical trials, pentoxifylline plus vitamin E should be considered as an option in patients with symptomatic RIF.

scholarly journals Chelation of lysosomal iron protects against ionizing radiation

2010 ◽  
Vol 432 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Carsten Berndt ◽  
Tino Kurz ◽  
Markus Selenius ◽  
Aristi P. Fernandes ◽  
Margareta R. Edgren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Iron Chelator ◽  
Radiation Sensitivity ◽  
Redox Active ◽  
Lung Malignancies ◽  
Life Threatening ◽  
Radiation Induced ◽  
Modifying Effect ◽  
Malignant Lung Tumours

Ionizing radiation causes DNA damage and consequent apoptosis, mainly due to the production of hydroxyl radicals (HO•) that follows radiolytic splitting of water. However, superoxide (O2•−) and H2O2 also form and induce oxidative stress with resulting LMP (lysosomal membrane permeabilization) arising from iron-catalysed oxidative events. The latter will contribute significantly to radiation-induced cell death and its degree largely depends on the quantities of lysosomal redox-active iron present as a consequence of autophagy and endocytosis of iron-rich compounds. Therefore radiation sensitivity might be depressed by lysosome-targeted iron chelators. In the present study, we have shown that cells in culture are significantly protected from ionizing radiation damage if initially exposed to the lipophilic iron chelator SIH (salicylaldehyde isonicotinoyl hydrazone), and that this effect is based on SIH-dependent lysosomal stabilization against oxidative stress. According to its dose-response-modifying effect, SIH is a most powerful radioprotector and a promising candidate for clinical application, mainly to reduce the radiation sensitivity of normal tissue. We propose, as an example, that inhalation of SIH before each irradiation session by patients undergoing treatment for lung malignancies would protect normally aerated lung tissue against life-threatening pulmonary fibrosis, whereas the sensitivity of malignant lung tumours, which usually are non-aerated, will not be affected by inhaled SIH.

scholarly journals Comparing the Radioprotective Effects of Brewed Rosa damascena and Vitamin E on Ionizing Radiation-Induced Chromosomal Aberrations in Human Peripheral Blood Lymphocytes Using Micronucleus Assay in Binucleated Cells

2020 ◽  
Vol 26 (1) ◽  
pp. 14-23
Author(s):  
Elham Khanirad ◽  
◽  
Farhang Haddad ◽  
Shokouhozaman Soleymanifard ◽  
◽  
...  
Keyword(s):  
Vitamin E ◽  
Ionizing Radiation ◽  
Chromosomal Aberrations ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Micronucleus Assay ◽  
Peripheral Blood Lymphocytes ◽  
Rosa Damascena ◽  
Blood Lymphocytes ◽  
Radiation Induced

Aims: For occupational and therapeutic reasons, many people are exposed to the harmful effects of Ionizing Radiation (IR) including Chromosomal Aberrations (CA) every day. Radioprotective agents are able to reduce these damages through mechanisms such as scavenging free radical, donating hydrogen to damaged molecules and increasing activity of antioxidant enzymes. Medicinal plants, traditionally used in different societies, have special advantages due to their low side effects and cost-effectiveness compared to the chemical radioprotectors. Rosa damascena is one of these plants that is widely used in traditional medicine. The aim of this study was to investigate the radioprotective effects of brewed Rosa damascena in comparison with Vitamin E. Methods & Materials: In this experimental study, the radioprotective effect of 1-week use of brewed Rosa damascena on the CA induced by 2 Gy IR in comparison with vitamin E in peripheral blood lymphocytes of 10 volunteers, 1, 24, and 96 h as well as one week after the last intake was investigated using binucleated cell micronucleus assay. Findings: The use of brewed Rosa damascena 1 h after the last intake could significantly reduce the frequency of micronuclei. This result was similar to the effect of vitamin E at the same time. Conclusion: Brewed Rosa damascena is able to protect cells from IR-induced damages and can be used as a cheaper radioprotector with the possibility of daily use compared to vitamin E.

scholarly journals Mitigation of radiation-induced gastro-intestinal injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kavya Venkateswaran ◽  
Anju Shrivastava ◽  
Paban K. Agrawala ◽  
Ashok K. Prasad ◽  
Sagolsem Chandrika Devi ◽  
...  
Keyword(s):  
Intestinal Injury ◽  
Epithelial Regeneration ◽  
Cycle Arrest ◽  
Survival Pathways ◽  
Life Threatening ◽  
Important Regulator ◽  
Radiation Induced ◽  
Total Body ◽  
Underlying Mechanisms ◽  
Stimulation Of

Abstract Radiation-induced intestinal injury (RIII) constitutes a crucial clinical element of acute radiation syndrome with life-threatening implications posing challenges in devising effective medical countermeasures. Herein, we report the potential of 7, 8-diacetoxy-4-methylthiocoumarin (DAMTC) to mitigate RIII following total-body irradiation (TBI) in C57BL/6 mice and underlying mechanisms. Administration of DAMTC 24 hours post TBI facilitated structural reconstitution and restoration of functional absorption linked to alleviation of radiation-induced apoptotic death of intestinal crypt progenitor/stem (ICPS) and villus stromal cells through induction of Bcl-2 family-mediated anti-apoptotic signalling. Reduction in TBI-induced DNA damage accumulation coupled with inhibition of cell cycle arrest through stimulation of anti-p53- and anti-p21-dependent synergistic signalling protected ICPS cells from radiation injury. Enhanced proliferation of crypt stem cells, induction of anti-oxidant defence, subjugation of TBI-induced lipid peroxidation and phenotypic polarization of intestinal macrophages to anti-inflammatory M2 class underlie amelioration of RIII. Stimulation of multiple mitigative signalling processes by DAMTC appeared to be associated with enhanced protein acetylation, an important regulator of cellular responses to radiation damage. Our findings establish the mitigative potential of DAMTC against RIII by hyper-acetylation-mediated epigenetic regulation, which triggers axes of anti-apoptotic and pro-survival pathways, enabling proliferation and maintenance of ICPS cells leading to epithelial regeneration.

scholarly journals Concentration-Dependent Protection by Ethanol Extract of Propolis againstγ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
A. Montoro ◽  
J. F. Barquinero ◽  
M. Almonacid ◽  
A. Montoro ◽  
N. Sebastià ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Antioxidant Activities ◽  
Cytogenetic Study ◽  
Radical Scavenging ◽  
Ethanol Extract ◽  
Negative Exponential Function ◽  
Radiation Induced ◽  
Maximum Protection ◽  
Negative Exponential

Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect,in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 μg mL−1and then exposed to 2 Gyγ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 μg mL−1of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

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