Publications by authors named "Mohsen Cheki"

28 Publications

  • Page 1 of 1

The radioprotective effect of melatonin against radiation-induced DNA double-strand breaks in radiology.

J Cancer Res Ther 2020 Dec;16(Supplement):S59-S63

Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences and Health Services, Tehran, Iran.

Objective: The objective of this study is to observe the effect of 100-mg melatonin in reducing the levels of double-strand breaks (DSB) induced by 10 mGy and 100 mGy X-ray in peripheral lymphocyte applying H2AX immunofluorescence microscopy and comparing the different efficacies of melatonin ingestion 1 and 2 h before irradiation.

Materials And Methods: Informed consent was obtained from five healthy males, nonathlete, and nonsmoking human volunteers aged between 25 and 35 years. Each volunteer was given a single oral dose of 100 mg melatonin at 9 a.m. Blood samples were collected in vacutainer tubes (without any preservative to separate the serum, and with heparin as an anticoagulant for separating leukocytes for in vitro exposure to gamma radiation) 5-10 min before then 1 and 2 h after melatonin ingestion. Afterward, each sample was subdivided into nonirradiated and irradiated groups (10 mGy and 100 mGy). After irradiation, lymphocytes of samples were separated. The isolated lymphocytes in each group were permeabilized for DSB assessment and stained against the phosphorylated histone variant γH2AX.

Results: Melatonin ingestion 1 and 2 h before irradiation caused a significant reduction in γH2AX foci. Results further indicate that the change in ingestion of melatonin from 1 to 2 h before exposure had no significant effect. In addition, melatonin administration showed no side effects.

Conclusion: The present study showed that melatonin will prove effective in radioprotection against ionizing radiation (IR)-induced DNA damage in human lymphocytes. Our results suggest ingestion of 100-mg melatonin by patients before exposure to IR in radiology.
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http://dx.doi.org/10.4103/jcrt.JCRT_370_18DOI Listing
December 2020

The protective effect of herniarin on genotoxicity and apoptosis induced by cisplatin in bone marrow cells of rats.

Drug Chem Toxicol 2020 Nov 3:1-6. Epub 2020 Nov 3.

Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. The aim of the present study was to investigate the effects of herniarin on genotoxicity and apoptosis induced by cisplatin in rat bone marrow cells. The experimental rats were treated with four different doses of herniarin (50, 100, 200, and 400 mg/kg.) for seven consecutive days. The cisplatin (5 mg/kg, i.p.) was injected into mice 1 h after the last oral herniarin administration on the seventh day. The protective effects of herniarin were investigated by hematological test, flow cytometry, micronucleus assay, and reactive oxygen species (ROS) level analysis. Herniarin caused a marked reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after exposure to cisplatin at doses of 200 and 400 mg/kg. Furthermore, herniarin significantly increased the levels of both red and white blood cells in peripheral blood. Treatment of rats with herniarin before cisplatin, significantly decreased the percentage of apoptotic and necrotic cells and the ROS level in bone marrow cells. This study indicated that herniarin can be introduced as a new chemoprotective agent against cisplatin-induced genotoxicity in the future.
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http://dx.doi.org/10.1080/01480545.2020.1842883DOI Listing
November 2020

Melatonin a Promising Candidate for DNA Double-Stranded Breaks Reduction in Patients Undergoing Abdomen-Pelvis Computed Tomography Examinations.

Anticancer Agents Med Chem 2020 ;20(7):859-864

Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background And Objective: Cancer incidence is 24% higher in children and young adults exposed to Computed Tomography (CT) scans than those unexposed. Non-repairing of ionizing radiation-induced DNA Double-Strand Breaks (DSBs) can initiate carcinogenesis. In the present study, we aimed to investigate the radioprotective potential of melatonin against DSBs in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations.

Methods: This double-blind, placebo-controlled clinical trial was conducted on thirty patients. These patients were divided into two groups; group one (control) patients who have undergone the CT examination received a single oral dose of placebo, while in group two, patients received a single oral dose of 100mg melatonin. In both the groups, blood samples were collected 5-10min before and 30 minutes after the CT examination. The lymphocytes from these samples were isolated and DSBs were analyzed using γH2AX immunofluorescence microscopy.

Results: Compared to the control group, the use of melatonin 1h before the CT examination caused a significant reduction in γH2AX-foci, indicating a reduction in DSBs. In addition, no side effect was observed in patients following 100mg melatonin administration.

Conclusion: For the first time, this study has shown that melatonin has protective effects against radiationinduced genotoxicity in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations. Therefore, melatonin can be considered as a promising candidate for reducing DSBs in patients undergoing abdomen-pelvis CT examinations.
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http://dx.doi.org/10.2174/1871521409666200324101701DOI Listing
January 2020

Evaluating the principles of radiation protection in diagnostic radiologic examinations: collimation, exposure factors and use of protective equipment for the patients and their companions.

J Med Radiat Sci 2020 Jun 9;67(2):119-127. Epub 2020 Mar 9.

Faculty of Paramedicine, Department of Radiologic Technology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Introduction: Producing appropriate diagnostic images along with patient radiation protection is the goal of radiography. Due to the advancements of radiography, concerns about observing the principles of radiation protection exist. Therefore, this study aimed to evaluate the observance of the principles of radiation protection in radiographic examinations with emphasis on field size collimation, suitability of exposure factors and the use of protective equipment for the patients and their companions.

Methods: Using a cross-sectional study design, two radiography students on their final year of study observed 100 radiographic examinations from the imaging departments of five educational hospitals. The SPSS version 24 software was used to analyse the results.

Results: The radiation field collimation was obtained in 46% of the studied radiographs. Patients had companions present during the examination in 26% of the studies; however, protective equipment was only used for 4% of the patients' companions, and no protective equipment was applied for patients. The observance rate of the various principles of radiation protection including field size restriction, the use of protective equipment for the patients and their companions, and suitability of the selected exposure factors was on average 44.6%.

Conclusion: The observance rate of the principles of radiation protection was insufficient in the studied educational hospitals, specifically in field size collimation and the use of protective equipment for the patients and their companions. Therefore, emphasis on the strict implementation of the radiation protection guidelines and continuous training of radiographers are required.
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http://dx.doi.org/10.1002/jmrs.384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276186PMC
June 2020

Evaluating the protective effect of resveratrol, Q10, and alpha-lipoic acid on radiation-induced mice spermatogenesis injury: A histopathological study.

Int J Reprod Biomed 2019 Dec 30;17(12):907-914. Epub 2019 Dec 30.

Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran.

Background: Testis is one of the most sensitive organs against the toxic effect of ionizing radiation. Exposure to even a low dose of radiation during radiotherapy, diagnostic radiology, or a radiological event could pose a threat to spermatogenesis. This may lead to temporary or permanent infertility or even transfer of genomic instability to the next generations.

Objective: In this study, we evaluated the protective effect of treatment with three natural antioxidants; resveratrol, alpha lipoic acid, and coenzyme Q10 on radiation-induced spermatogenesis injury.

Materials And Methods: 30 NMRI mice (6-8 wk, 30 5 gr) were randomly divided into six groups (n = 5/each) as 1) control; 2) radiation; 3) radiation + resveratrol; 4) radiation + alpha lipoic acid; 5) radiation + resveratrol + alpha lipoic acid; and 6) radiation+ Q10. Mice were treated with 100 mg/kg resveratrol or 200 mg/kg alpha lipoic acid or a combination of these drugs. Also, Q10 was administered at 200 mg/kg. All treatments were performed daily from two days before to 30 min before irradiation. Afterward, mice were exposed to 2 Gy Co gamma rays; 37 days after irradiation, the testicular samples were collected and evaluated for histopathological parameters.

Results: Results showed that these agents are able to alleviate some toxicological parameters such as basal lamina and epididymis decreased sperm density. Also, all agents were able to increase Johnsen score. However, they could not protect against radiation-induced edema, atrophy of seminiferous tubules, and hyperplasia in Leydig cells.

Conclusion: This study indicates that resveratrol, alpha-lipoic acid, and Q10 have the potential to reduce some of the side effects of radiation on mice spermatogenesis. However, they cannot protect Leydig cells as a source of testosterone and seminiferous tubules as the location of sperm maturation.
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http://dx.doi.org/10.18502/ijrm.v17i12.5791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6943799PMC
December 2019

The Screening of Renoprotective Agents by 99mTc-DMSA: A Review of Preclinical Studies.

Curr Radiopharm 2019 ;12(3):211-219

Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Nephrotoxicity is a prevalent consequence of cancer treatment using radiotherapy and chemotherapy or their combination. There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although these methods are used for the try-out of renoprotective factors, these methods are invasive and time-consuming, and also, lack the necessary sensitivity for primary diagnosis. Quantitative renal 99mTc-DMSA scintigraphy is a noninvasive, precise and sensitive radionuclide technique which is used to assess the extent of kidney damage, so that the extent of injury to the kidney will be indicated by the renal uptake rate of 99mTc-DMSA in the kidney. In addition, this scintigraphy evaluates the effect of the toxic agents by quantifying the alterations in the biodistribution of the radiopharmaceutical.

Conclusion: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy.
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http://dx.doi.org/10.2174/1874471012666190717142316DOI Listing
February 2020

The Radioprotective Effect of Combination of Melatonin and Metformin on Rat Duodenum Damage Induced by Ionizing Radiation: A Histological Study.

Adv Biomed Res 2019 21;8:51. Epub 2019 Aug 21.

Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Science, International Campus, Tehran, Iran, Misan, Iraq.

Background: Radiation toxicity is one of the major concerns for patients with gastrointestinal cancers that undergo radiotherapy. Duodenum is one of the most radiosensitive parts of gastrointestinal system that may be exposed to a high dose of radiation during radiotherapy for some cancers. The development or identification of appropriate radioprotectors with less toxicity is an interesting aim in radiobiology for clinical radiotherapy applications. In the present study, we aimed to evaluate the radioprotective effect of melatonin and metformin combination in rat's duodenum. In addition, we compared our results with the radioprotective effect of melatonin, when administered alone.

Materials And Methods: Thirty male rats were divided into six groups: control, melatonin treatment, melatonin plus metformin treatment, whole-body irradiation, irradiation with melatonin treatment, and irradiation with melatonin plus metformin treatment. Irradiation was performed with 10 Gy cobalt-60 gamma rays, while 100 mg/kg of melatonin and metformin were administered 24 h before to 72 h after irradiation. After 3.5 days, their duodenum tissues were removed for histopathological evaluation.

Results: Irradiation of rats led to mild-to-moderate mucositis signs, infiltration of inflammatory cells, necrosis, and damage to Brunner's glands and reduction of goblet cells. Melatonin was able to alleviate these damages, while melatonin plus metformin could reduce some radiation toxicity signs.

Conclusion: Administration of melatonin plus metformin could reduce mucositis in duodenum. However, the administration of melatonin is more effective for mitigation of duodenal injury compared with melatonin plus metformin.
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http://dx.doi.org/10.4103/abr.abr_68_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712895PMC
August 2019

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

Antiinflamm Antiallergy Agents Med Chem 2020 ;19(2):180-189

Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Science, International Campus, Tehran, Iran.

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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http://dx.doi.org/10.2174/1871523018666190718161928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475942PMC
January 2021

Protection from ionizing radiation-induced genotoxicity and apoptosis in rat bone marrow cells by HESA-A: a new herbal-marine compound.

J Bioenerg Biomembr 2019 10 6;51(5):371-379. Epub 2019 Aug 6.

Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

HESA-A is an herbal-marine compound which improves the quality of life of end-stage cancer patients. The aim of the present study was to evaluate the possible protective effect of HESA-A against IR-induced genotoxicity and apoptosis in rat bone marrow. Rats were given HESA-A orally at doses of 150 and 300 mg/kg body weight for seven consecutive days. On the seventh day, the rats were irradiated with 4 Gy X-rays at 1 h after the last oral administration. The micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis and flow cytometry were used to assess radiation antagonistic potential of HESA-A. Administration of 150 and 300 mg/kg of HESA-A to irradiated rats significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs), and also increased PCE/(PCE + NCE) ratio in bone marrow cells. Moreover, pretreatment of irradiated rats with HESA-A (150 and 300 mg/kg) significantly decreased ROS level and apoptosis in bone marrow cells, and also increased white blood cells count in peripheral blood. For the first time in this study, it was observed that HESA-A can have protective effects against radiation-induced genotoxicity and apoptosis in bone marrow cells. Therefore, HESA-A can be considered as a candidate for future studies to reduce the side effects induced by radiotherapy in cancer patients.
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http://dx.doi.org/10.1007/s10863-019-09808-5DOI Listing
October 2019

Glucosamine Protects Rat Bone Marrow Cells Against Cisplatin-induced Genotoxicity and Cytotoxicity.

Anticancer Agents Med Chem 2019 ;19(14):1695-1702

Department of Biosciences and Biotechnology, Malek-Ashtar University of Technology, Tehran, Iran.

Background And Objective: Glucosamine is a widely prescribed dietary supplement used in the treatment of osteoarthritis. In the present study, the chemoprotectant ability of glucosamine was evaluated against cisplatin-induced genotoxicity and cytotoxicity in rat bone marrow cells.

Methods: Glucosamine was orally administrated to rats at doses of 75 and 150 mg/kg body weight for seven consecutive days. On the seventh day, the rats were treated with a single injection of cisplatin (5 mg/kg, i.p.) at 1h after the last oral administration. The cisplatin antagonistic potential of glucosamine was assessed by micronucleus assay, Reactive Oxygen Species (ROS) level analysis, hematological analysis, and flow cytometry.

Results: Glucosamine administration to cisplatin-treated rats significantly decreased the frequencies of Micronucleated Polychromatic Erythrocytes (MnPCEs) and Micronucleated Normchromatic Erythrocytes (MnNCEs), and also increased PCE/(PCE+NCE) ratio in bone marrow cells. Furthermore, treatment of rats with glucosamine before cisplatin significantly inhibited apoptosis, necrosis and ROS generation in bone marrow cells, and also increased red blood cells count in peripheral blood.

Conclusion: This study shows glucosamine to be a new effective chemoprotector against cisplatin-induced DNA damage and apoptosis in rat bone marrow cells. The results of this study may be helpful in reducing the harmful effects of cisplatin-based chemotherapy in the future.
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http://dx.doi.org/10.2174/1871520619666190704164126DOI Listing
August 2020

Metformin attenuates cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells.

Drug Chem Toxicol 2019 May 9:1-8. Epub 2019 May 9.

c Department of Basic Sciences, Histology Section, Faculty of Veterinary Medicine , Shahid Chamran University of Ahvaz , Ahvaz , Iran.

Metformin is widely used as an oral hypoglycemic drug in the management of type 2 diabetes mellitus. This study evaluated the possible protective effects of metformin against cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Two different doses of metformin (50 and 100 mg/kg b.w.) were administered orally to experimental animals for seven consecutive days. On the seventh day, the rats were exposed to cisplatin (5 mg/kg, i.p.) 1 h after the last oral metformin administration. Rats in the control group were treated orally with 10 ml/kg PBS for 7 consecutive days and a single intraperitoneal injection of saline (0.9%) on the 7th day. The antagonistic effects of metformin against cisplatin were evaluated using micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis, and flow cytometry. Treatment with 50 and 100 mg/kg metformin before cisplatin injection produced a significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after cisplatin treatment with a corresponding increase in the PCE/(PCE + NCE) ratio. Moreover, metformin markedly elevated the levels of both red and white blood cells in peripheral blood and decreased the percentage of apoptotic cells and the ROS level in bone marrow cells of rats treated with cisplatin. The data suggest that metformin has potential chemoprotective properties in rat bone marrow after cisplatin treatment, which support its candidature as a potential chemoprotective agent for cancer patients undergoing chemotherapy.
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http://dx.doi.org/10.1080/01480545.2019.1609024DOI Listing
May 2019

Metformin Protects Against Radiation-Induced Pneumonitis and Fibrosis and Attenuates Upregulation of Dual Oxidase Genes Expression.

Adv Pharm Bull 2018 Nov 29;8(4):697-704. Epub 2018 Nov 29.

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran.

Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat's lung tissues. 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4-DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.
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http://dx.doi.org/10.15171/apb.2018.078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311649PMC
November 2018

Stem Cell Tracing Through MR Molecular Imaging.

Tissue Eng Regen Med 2018 Jun 16;15(3):249-261. Epub 2018 Jan 16.

9Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 194193311 Iran.

Stem cell therapy opens a new window in medicine to overcome several diseases that remain incurable. It appears such diseases as cardiovascular disorders, brain injury, multiple sclerosis, urinary system diseases, cartilage lesions and diabetes are curable with stem cell transplantation. However, some questions related to stem cell therapy have remained unanswered. Stem cell imaging allows approval of appropriated strategies such as selection of the type and dose of stem cell, and also mode of cell delivery before being tested in clinical trials. MRI as a non-invasive imaging modality provides proper conditions for this aim. So far, different contrast agents such as superparamagnetic or paramagnetic nanoparticles, ultrasmall superparamagnetic nanoparticles, fluorine, gadolinium and some types of reporter genes have been used for imaging of stem cells. The core subject of these studies is to investigate the survival and differentiation of stem cells, contrast agent's toxicity and long term following of transplanted cells. The promising results of and some clinical trial studies may raise hope for clinical stem cells imaging with MRI.
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http://dx.doi.org/10.1007/s13770-017-0112-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171680PMC
June 2018

Protection Against Radiation-Induced Micronuclei in Rat Bone Marrow Erythrocytes by Curcumin and Selenium L-Methionine.

Iran J Med Sci 2018 Nov;43(6):645-652

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Background: The search for potent radioprotective agents for the amelioration of radiation side effect is an important aim in radiobiology. The present study aimed to evaluate the effects of curcumin and seleno-L-methionine against radiation-induced micronucleus formation in rat bone marrow.

Methods: In total, 40 male rats were divided into 8 groups (n=5 each), including control, curcumin or seleno-L-methionine treated alone or in combination, 2 Gy irradiation, irradiation of treated groups with curcumin or seleno-L-methionine or their combination. Curcumin was administrated orally and seleno-L-methionine was injected intraperitoneally 24 hours before irradiation. The frequency of micronucleated normochromatic erythrocytes (MnNCEs) and micronucleated polychromatic erythrocytes (MnPCEs) was scored in 5,000 polychromatic erythrocytes (PCEs) and the cell proliferation ratio [(PCE/(PCE+NCE); NCE=normochromatic erythrocytes] was calculated for each treatment group. Data were analyzed by the SPSS software version 16.0 and P<0.05 was considered as statistically significant differences.

Results: Pretreatment with curcumin and seleno-L-methionine before irradiation reduced the frequency of MnPCEs and MnNCEs (P=0.01) and increased the cell proliferation ratio. Moreover, the results showed that this pretreatment reduced the frequency of MnPCEs with a protection factor (PF) of 1.2 and 1.6, respectively. The combination of curcumin and seleno-L-methionine in reducing MnPCEs and MnNCEs was not more effective than each agent alone, while improved cell proliferation ratio.

Conclusion: Both curcumin and seleno-L-methionine showed potent protection against radiation induced MN in bone marrow cells. The combination of the two agents further ameliorates this activity, thus leading to improve bone marrow protection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230935PMC
November 2018

Mechanisms for Radioprotection by Melatonin; Can it be Used as a Radiation Countermeasure?

Curr Mol Pharmacol 2019 ;12(1):2-11

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) have been proved. However, in the recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products.

Discussion: Moreover, melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes etc. Animal studies have confirmed that melatonin is able to alleviate radiation-induced cell death via inhibiting pro-apoptosis and upregulation of anti-apoptosis genes. These properties are very interesting for clinical radiotherapy applications, as well as mitigation of radiation injury in a possible radiation disaster. An interesting property of melatonin is mitochondrial ROS targeting that has been proposed as a strategy for mitigating effects in radiosensitive organs, such as bone marrow, gastrointestinal system and lungs. However, there is a need to prove the mitigatory effects of melatonin in experimental studies.

Conclusion: In this review, we aim to clarify the molecular mechanisms of radioprotective effects of melatonin, as well as possible applications as a radiation countermeasure in accidental exposure or nuclear/radiological disasters.
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http://dx.doi.org/10.2174/1874467211666180802164449DOI Listing
June 2019

Metformin Protects Against Radiation-Induced Heart Injury and Attenuates the Upregulation of Dual Oxidase Genes Following Rat's Chest Irradiation.

Int J Mol Cell Med 2018 21;7(3):193-202. Epub 2018 Oct 21.

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Radiation-induced heart toxicity is one of the serious side effects after a radiation disaster or radiotherapy for patients with chest cancers, leading to a reduction in the quality of life of the patients. Evidence has shown that infiltration of inflammatory cells plays a key role in the development of functional damages to the heart via chronic upregulation of some pro-fibrotic and pro-inflammatory cytokines. These changes are associated with continuous free radical production and increased stiffness of heart muscle. IL-4 and IL-13 are two important pro-fibrotic cytokines which contribute to the side effects of ionizing radiation exposure. Recent studies have proposed that IL-4 through upregulation of , and IL-13 via stimulation of gene expression, are involved in the development of radiation late effects. In the present study, we aimed to detect changes in the expression of these pathways following irradiation of rat's heart. Furthermore, we evaluated the possible protective effect of metformin on the development of these abnormal changes. 20 male rats were divided into 4 groups (control, radiation, metformin treated, metformin + radiation). These rats were irradiated with 15 Gy Co gamma rays, and sacrificed after 10 weeks for evaluation of the changes in the expression of , , and . In addition, the levels of IL-4 and IL-13 cytokines, as well as infiltration of macrophages and lymphocytes were detected. Results showed an upregulation of both and pathways in the presence of metformin, while the level of IL-13 did not show any significant change. This was associated with infiltration of macrophages and lymphocytes. Also, treatment with metformin could significantly attenuate accumulation of inflammatory cells, and upregulate these pathways. Therefore, uppression of dual oxidase genes by metformin may be a contributory factor to its protective effect.
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http://dx.doi.org/10.22088/IJMCM.BUMS.7.3.193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744616PMC
October 2018

Radiation Protection and Mitigation by Natural Antioxidants and Flavonoids: Implications to Radiotherapy and Radiation Disasters.

Curr Mol Pharmacol 2018 ;11(4):285-304

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background: Nowadays, ionizing radiations are used for various medical and terroristic aims. These purposes involve exposure to ionizing radiations. Hence, people are at risk for acute or late effects. Annually, millions of cancer patients undergo radiotherapy during their course of treatment. Also, some radiological or nuclear events in recent years pose a threat to people, hence the need for radiation mitigation strategies. Amifostine, the first FDA approved radioprotector, has shown some toxicities that limit its usage and efficiency. Due to these side effects, scientists have researched for other agents with less toxicity for better radioprotection and possible mitigation of the lethal effects of ionizing radiations after an accidental exposure. Flavonoids have shown promising results for radioprotection and can be administered in higher doses with less toxicity. Studies for mitigation of ionizing radiation-induced toxicities have concentrated on natural antioxidants. Detoxification of free radicals, management of inflammatory responses and attenuation of apoptosis signaling pathways in radiosensitive organs are the main mechanisms for radiation protection and mitigation with flavonoids and natural antioxidants. However, several studies have proposed that a combination in the form of some antioxidants may alleviate radiation toxicities more effectively in comparison to a single form of antioxidants.

Conclusion: In this review, we focus on recent findings about natural radioprotectors and mitigators which are clinically applicable for radiotherapy patients, as well as injured people in possible radiation accidents.
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http://dx.doi.org/10.2174/1874467211666180619125653DOI Listing
April 2019

Radiation-induced inflammation and autoimmune diseases.

Mil Med Res 2018 03 20;5(1). Epub 2018 Mar 20.

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Zip code: 6714869914, Iran.

Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.
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http://dx.doi.org/10.1186/s40779-018-0156-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859747PMC
March 2018

Metformin: Prevention of genomic instability and cancer: A review.

Mutat Res Genet Toxicol Environ Mutagen 2018 Mar 31;827:1-8. Epub 2018 Jan 31.

Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

The diabetes drug metformin can mitigate the genotoxic effects of cytotoxic agents and has been proposed to prevent or even cure certain cancers. Metformin reduces DNA damage by mechanisms that are only incompletely understood. Metformin scavenges free radicals, including reactive oxygen species and nitric oxide, which are produced by genotoxicants such as ionizing or non-ionizing radiation, heavy metals, and chemotherapeutic agents. The drug may also increase the activities of antioxidant enzymes and inhibit NADPH oxidase, cyclooxygenase-2, and inducible nitric oxide synthase, thereby limiting macrophage recruitment and inflammatory responses. Metformin stimulates the DNA damage response (DDR) in the homologous end-joining, homologous recombination, and nucleotide excision repair pathways. This review focuses on the protective properties of metformin against genomic instability.
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http://dx.doi.org/10.1016/j.mrgentox.2018.01.007DOI Listing
March 2018

COX-2 in Radiotherapy: A Potential Target for Radioprotection and Radiosensitization.

Curr Mol Pharmacol 2018 ;11(3):173-183

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran.

Background: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment.

Discussion: Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the activation of this enzyme can increase resistance of malignant cells to radiotherapy. Hence, the inhibition of COX-2 has been proposed for better therapeutic response and amelioration of normal tissues. Celecoxib is one of the most studied COX-2 inhibitor for radiosensitization and radioprotection, while some other inhibitors have shown interesting results.

Conclusion: In this review, we describe the role of COX-2 in radiation normal tissue injury as well as irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2 induced tumor resistance to radiotherapy and the potential role of COX-2 inhibition are discussed.
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http://dx.doi.org/10.2174/1874467211666180219102520DOI Listing
December 2018

Preliminary Human Radiation Dose Estimates of PET Renal Agents, Para-F-Fluorohippuric Acid and Ortho-I-Iodohippuric Acid from Rat Biodistribution Data.

Curr Radiopharm 2018 ;11(1):58-63

Department of Pharmaceutical Sciences, College of Pharmacy, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States.

Background: Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the biodistribution data reported in healthy rats. The results were compared with the absorbed dose data of technetium-99m-mercaptoacetyltriglycine (99mTc- MAG3) as documented in the International Commission on Radiological Protection (ICRP) publication 80.

Methods: The medical internal radiation dose (MIRD) formula was applied to extrapolate data from rats to human and to project the absorbed radiation dose for various organs in humans. S factor was calculated by Monte-Carlo N-particle (MCNP) simulation.

Results: Our dose prediction shows that an injection of 18F-PFH or 124I-OIH in humans would result in an estimated effective absorbed dose of 0.09 or 0.17 µSv/MBq respectively for whole body, which is about 135 or 73 times respectively lower than that obtained with an injection of 99mTc-MAG3. All organs except kidneys would receive an estimated effective absorbed dose of <0.1 µSv/MBq for 18F-PFH or 124I-OIH. Kidneys would receive a dose of 0.83 or 0.77 µSv/MBq respectively for 18F-PFH or 124I-OIH.

Conclusions: Our results indicate that 18F-PFH and 124I-OIH would deliver much safer levels and lower radiation doses to the patients compared to 99mTc-MAG3 and warrants a clinical trial to estimate the radiation doses more accurately.
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http://dx.doi.org/10.2174/1874471011666180212123534DOI Listing
August 2018

Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy.

Curr Radiopharm 2018 ;11(1):34-45

Scientific Research Department, Uniformed Services University of Health Sciences (USUHS), Armed Forces Radiobiology Research Institute (AFRRI), Bethesda, MD, 20889-5603, United States.

Background: Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remains to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence. The non-targeted effect in radiobiology refers to a dynamic complex response in non-irradiated tissues caused by the release of presumably of clastogenic factors from irradiated cells. Although, most of these responses in non-targeted tissues have marked similarities to irradiated tissues, other studies have shown some differences. Also, the non-targeted effect has shown sex and tissue specificity that are seen in irradiated tissues too. So far, several studies have been conducted to depict mechanisms that may be involved in this phenomenon. Epigenetic dysfunctions, DNA damage and cell death are responsible for initiation of several signaling pathways that finally result in secretion of clastogenic factors. Moreover, studies have shown that damage to both nucleus and mitochondrial DNA, membrane and some organelles is involved. Oxidized DNA associated with other cell death factors stimulates secretion of inflammatory as well as some anti-inflammatory cytokines from irradiated area. Additionally, oxidative stress that results in damage to cellular structures to include cell membranes can affect secretion of exosomes and miRNAs. These bystander effect exogenous mediators migrate to distant tissues and stimulate various signaling pathways which can lead to changes in immune responses, epigenetic modulations and radiation carcinogenesis.

Conclusion: In this review, we focus on descriptive and hierarchical events with emphasis on the molecular and functional interactions of ionizing radiation with cells to the mechanisms involved in cancer induction in non-targeted tissues.
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http://dx.doi.org/10.2174/1874471011666171229123130DOI Listing
August 2018

Primary radiation dosimetry of a novel PET radiopharmaceutical Ga-NODAGA-glycine in comparison with Tc-DTPA in renal studies.

Hell J Nucl Med 2017 Sep-Dec;20(3):241-246. Epub 2017 Nov 27.

Department of Radiologic Technology, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Objective: In this study, we tried to estimate human absorbed dose of Ga-NODAGA-glycine as a new potential positron emission tomography (PET) renal agent based on the biodistribution data reported in healthy rats, and compare our estimation with the available absorbed dose data from technetium-99m-diethylenetriaminepentaacetic acid (Tc-DTPA).

Subjects And Methods: The medical internal radiation dose (MIRD) formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. S factor calculated by Monte-Carlo N-particle (MCNP) simulation and also this factor has been taken from the tables presented in MIRD pamphlet No.11. Hence, two radiation absorbed dose were calculated for organs.

Results: Our dose prediction shows that an 185MBq injection of gallium-68-1,4,7-triazacyclononane-1-γ-glutamylglycine-4,7-diacetic acid (Ga-NODAGA-glycine) in humans might result in an estimated absorbed dose of 0.063mGy in the whole body when S factor calculated by MCNP simulation. The highest absorbed doses are observed in kidneys, lungs, spleen, liver, and red marrow with 3.510, 0.453, 0.335, 0.268, and 0.239mGy, respectively. In addition to, the estimated absorbed dose for total body after injection of 185MBq of Ga-NODAGA-glycine is 0.053mGy when S factor has been taken from MIRD pamphlet No.11. The highest absorbed doses are observed in kidneys, lungs, liver, spleen, and red marrow with 3.110, 0.438, 0.209, 0.203, and 0.203mGy, respectively. Comparison between human absorbed dose estimation for Ga-NODAGA-glycine and Tc-DTPA indicated that the absorbed dose of the most organs after injection of Tc-DTPA is higher than the amount after Ga-NODAGA-glycine.

Conclusion: The results showed that Ga-NODAGA-glycine delivers lower dose to the patients. Also due to its application in PET (which offers higher sensitivity and spatial resolution compared to planar or SPET), Ga-NODAGA-glycine would be a superior choice than Tc-DTPA for renography and impose less radiation doses to patients.
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http://dx.doi.org/10.1967/s002449910609DOI Listing
February 2018

Targeting of Inflammation for Radiation Protection and Mitigation.

Curr Mol Pharmacol 2018 ;11(3):203-210

Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran.

Background: Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on.

Discussion: Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect. Inflammation in both irradiated and non-irradiated cells can trigger genomic instability, leading to increased risk of carcinogenesis. Targeting the inflammatory mediators has been an interesting idea for improving the therapeutic ratio throughout the reduction of normal tissue injury as well as an increase in tumor response to radiotherapy.

Conclusion: So far, various targets have been proposed for the amelioration of radiation toxicity in radiotherapy. Of different targets, NF-κB, COX-2, some of NADPH Oxidase subfamilies, TGF-β, p38 and the renin-angiotensin system have shown promising results. Interestingly, inhibition of these targets can help sensitize the tumor cells to the radiation treatment with some mechanisms such as suppression of angiogenesis and tumor growth as well as induction of apoptosis. In this review, we focus on recent advances on promising studies for targeting the inflammatory mediators in radiotherapy.
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http://dx.doi.org/10.2174/1874467210666171108165641DOI Listing
December 2018

Prophylactic role of some plants and phytochemicals against radio-genotoxicity in human lymphocytes.

J Cancer Res Ther 2016 Oct-Dec;12(4):1234-1242

Novin Medical Radiation Institute, Tehran, Iran.

Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.
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http://dx.doi.org/10.4103/0973-1482.172131DOI Listing
March 2017

The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes.

Mutat Res 2016 Oct 3;809:24-32. Epub 2016 Sep 3.

Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50μM for 2h and irradiated with 6MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow cytometry. Observations demonstrated a radiation-dose-dependent decrease in the percentage of cell viability after 24h. It was found that pretreatment with metformin (10 and 50μM) increased the percentage of cell viability. A highly significant dose modifying factor (DMF) 1.35 and 1.42 was observed for 10 and 50μM metformin, respectively. Metformin (10 and 50μM) pretreatment significantly decreased the frequency of dicentrics (DCs), acentric fragments (AFs), rings (RIs), micronuclei (MN), and nucleoplasmic bridges (NPBs) in irradiated human peripheral blood lymphocytes. Also, treatment with metformin (10 and 50μM) without irradiation did not increase the number of MN, NPBs, DCs, AFs, RIs, and did not show a cytostatic effect in the human peripheral blood lymphocytes. On the other hand, metformin treatment (10 and 50μM) 2h prior to irradiation significantly reduced X-radiation-induced apoptotic incidence in human lymphocytes. The present study demonstrates metformin to be an effective radioprotector against DNA damage and apoptosis induced by IR in human lymphocytes. These data have an important application for the protection of lymphocytes from the genetic damage and side-effects induced by radiotherapy in cancer patients.
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http://dx.doi.org/10.1016/j.mrgentox.2016.09.001DOI Listing
October 2016

Focal hot spot induced by a central subclavian line on bone scan.

Adv Biomed Res 2014 29;3:230. Epub 2014 Nov 29.

Department of Biology, Science and Research Branch, Islamic Azad University, Fars, Iran.

The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration) and the interpreting physicians should be aware of the impact of technical factors on image quality.
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http://dx.doi.org/10.4103/2277-9175.145723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260276PMC
December 2014

Estimation of Organ Absorbed Doses in Patients from (99m)Tc-diphosphonate Using the Data of MIRDose Software.

J Med Signals Sens 2012 Oct;2(4):231-4

Department of Medical Physics and Biomedical Engineering, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

The purpose of this study was to compare estimation of radiation absorbed doses to patients following bone scans with technetium-99m-labeled methylene diphosphonate (MDP) with the estimates given in MIRDose software. In this study, each patient was injected 25 mCi of (99m)Tc-MDP. Whole-body images from thirty patients were acquired by gamma camera at 10, 60, 90, 180 minutes after (99m)Tc-MDP injection. To determine the amount of activity in each organ, conjugate view method was applied on images. MIRD equation was then used to estimate absorbed doses in different organs of patients. At the end, absorbed dose values obtained in this study were compared with the data of MIRDose software. The absorbed doses per unit of injected activity (mGy/MBq × 10(-4)) for liver, kidneys, bladder wall and spleen were 3.86 ± 1.1, 38.73 ± 4.7, 4.16 ± 1.8 and 3.91 ± 1.3, respectively. The results of this study may be useful to estimate the amount of activity that can be administered to the patient and also showed that methods used in the study for absorbed dose calculation is in good agreement with the data of MIRDose software and it is possible to use by a clinician.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3662107PMC
October 2012