Exploring the efficacy of multi-flavored feature extraction with radiomics and deep features for prostate cancer grading on mpMRI.

BACKGROUND: The purpose of this study is to investigate the use of radiomics and deep features obtained from multiparametric magnetic resonance imaging (mpMRI) for grading prostate cancer. We propose a novel approach called multi-flavored feature extraction or tensor, which combines four mpMRI images using eight different fusion techniques to create 52 images or datasets for each patient. We evaluate the effectiveness of this approach in grading prostate cancer and compare it to traditional methods. METHODS: We used the PROSTATEx-2 dataset consisting of 111 patients' images from T2W-transverse, T2W-sagittal, DWI, and ADC images. We used eight fusion techniques to merge T2W, DWI, and ADC images, namely Laplacian Pyramid, Ratio of the low-pass pyramid, Discrete Wavelet Transform, Dual-Tree Complex Wavelet Transform, Curvelet Transform, Wavelet Fusion, Weighted Fusion, and Principal Component Analysis. Prostate cancer images were manually segmented, and radiomics features were extracted using the Pyradiomics library in Python. We also used an Autoencoder for deep feature extraction. We used five different feature sets to train the classifiers: all radiomics features, all deep features, radiomics features linked with PCA, deep features linked with PCA, and a combination of radiomics and deep features. We processed the data, including balancing, standardization, PCA, correlation, and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Finally, we used nine classifiers to classify different Gleason grades. RESULTS: Our results show that the SVM classifier with deep features linked with PCA achieved the most promising results, with an AUC of 0.94 and a balanced accuracy of 0.79. Logistic regression performed best when using only the deep features, with an AUC of 0.93 and balanced accuracy of 0.76. Gaussian Naive Bayes had lower performance compared to other classifiers, while KNN achieved high performance using deep features linked with PCA. Random Forest performed well with the combination of deep features and radiomics features, achieving an AUC of 0.94 and balanced accuracy of 0.76. The Voting classifiers showed higher performance when using only the deep features, with Voting 2 achieving the highest performance, with an AUC of 0.95 and balanced accuracy of 0.78. CONCLUSION: Our study concludes that the proposed multi-flavored feature extraction or tensor approach using radiomics and deep features can be an effective method for grading prostate cancer. Our findings suggest that deep features may be more effective than radiomics features alone in accurately classifying prostate cancer.

Radioproteomics modeling of metformin-enhanced radiosensitivity: an animal study.

PURPOSE: Metformin is considered as radiation modulator in both tumors and healthy tissues. Radiomics has the potential to decode biological mechanisms of radiotherapy response. The aim of this study was to apply radiomics analysis in metformin-induced radiosensitivity and finding radioproteomics associations of computed tomography (CT) imaging features and proteins involved in metformin radiosensitivity signaling pathways. MATERIALS AND METHODS: A total of 32 female BALB/c mice were used in this study and were subjected to injection of breast cancer cells. When tumors reached a mean volume of 150 mm3, mice were randomly divided into the four groups including Control, Metformin, Radiation, and Radiation + Metformin. Western blot analysis was performed after treatment to measure expression of proteins including AMPK-alpha, phospho-AMPK-alpha (Thr172), mTOR, phospho-mTOR (Ser2448), phospho-4EBP1 (Thr37/46), phospho-ACC (Ser79), and ß-actin. CT imaging was performed before treatment and at the end of treatment in all groups. Radiomics features extracted from segmented tumors were selected using Elastic-net regression and were assessed in terms of correlation with expression of the proteins. RESULTS: It was observed that proteins including phospho-mTOR, phospho-4EBP1, and mTOR had positive correlations with changes in tumor volumes in days 28, 24, 20, 16, and 12, while tumor volume changes at these days had negative correlations with AMPK-alpha, phospho-AMPK-alpha, and phospho-ACC proteins. Furthermore, median feature had a positive correlation with AMPK-alpha, phospho-ACC, and phospho-AMPK-alpha proteins. Also, Cluster shade feature had positive correlations with mTOR and p-mTOR. On the other hand, LGLZE feature had negative correlations with AMPK-alpha and phospho-AMPK-alpha. CONCLUSION: Radiomics features can decode proteins that involved in response to metformin and radiation, although further studies are warranted to investigate the optimal way to integrate radiomics into biological experiments.

A Computed Tomography-based Radiomics Analysis of Low-energy Proximal Femur Fractures in the Elderly Patients.

INTRODUCTION: Low-energy proximal femur fractures in elderly patients result from factors, like osteoporosis and falls. These fractures impose high rates of economic and social costs. In this study, we aimed to build predictive models by applying machine learning (ML) methods on radiomics features to predict low-energy proximal femur fractures. METHODS: Computed tomography scans of 40 patients (mean ± standard deviation of age = 71 ± 6) with low-energy proximal femur fractures (before a fracture occurs) and 40 individuals (mean ± standard deviation of age = 73 ± 7) as a control group were included. The regions of interest, including neck, trochanteric, and intertrochanteric, were drawn manually. The combinations of 25 classification methods and 8 feature selection methods were applied to radiomics features extracted from ROIs. Accuracy and the area under the receiver operator characteristic curve (AUC) were used to assess ML models' performance. RESULTS: AUC and accuracy values ranged from 0.408 to 1 and 0.697 to 1, respectively. Three classification methods, including multilayer perceptron (MLP), sequential minimal optimization (SMO), and stochastic gradient descent (SGD), in combination with the feature selection method, SVM attribute evaluation (SAE), exhibited the highest performance in the neck (AUC = 0.999, 0.971 and 0.971, respectively; accuracy = 0.988, 0.988, and 0.988, respectively) and the trochanteric (AUC = 1, 1 and 1, respectively; accuracy = 1, 1 and 1, respectively) regions. The same methods demonstrated the highest performance for the combination of the 3 ROIs' features (AUC = 1, 1 and 1, respectively; accuracy =1, 1 and 1, respectively). In the intertrochanteric region, the combination methods, MLP + SAE, SMO + SAE, and SGD + SAE, as well as the combination of the SAE method and logistic regression (LR) classification method exhibited the highest performance (AUC = 1, 1, 1 and 1, respectively; accuracy= 1, 1, 1 and 1, respectively). CONCLUSION: Applying machine learning methods to radiomics features is a powerful tool to predict low-energy proximal femur fractures. The results of this study can be verified by conducting more research on bigger datasets.

Investigating the attenuating effect of telmisartan against radiation-induced intestinal injury using 18F-FDG micro-PET imaging.

BACKGROUND AND OBJECTIVE: This study was aimed to investigate the ability of 18F-Fluro-deoxy-glucose (18F-FDG)-based micro-positron emission tomography (microPET) imaging to evaluate the efficacy of telmisartan, a highly selective angiotensin II receptor antagonist (ARA), in intestinal tissue recovery process after in vivo irradiation. METHODS: Male Balb/c mice were randomly divided into four groups of control, telmisartan, irradiation, and telmisartan + irradiation. A solution of telmisartan in phosphate-buffered saline (PBS) was administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. The mice were imaged using 18F-FDG microPET at 9 and 30 days post-irradiation. The 18F-FDG uptake in jejunum was determined according to the mean standardized uptake value (SUVmean) index. Tissues were also processed in similar time points for histological analysis. RESULTS: The 18F-FDG microPET imaging confirmed the efficacy of telmisartan as a potent attenuating agent for ionizing radiation-induced injury of intestine in mice model. The results were also in line with the histological analysis indicating that pretreatment with telmisartan reduced damage to the villi, crypts, and intestinal mucosa compared with irradiated and non-treated group from day 9 to 30 after irradiation. CONCLUSION: The results revealed that 18F-FDG microPET imaging could be a good candidate to replace time-consuming and invasive biological techniques for screening of radioprotective agents. These findings were also confirmed by histological examinations which indicated that telmisartan can effectively attenuates radiation injury caused by ionizing-irradiation.

The effects of medical linear accelerator X-rays on human peripheral blood lymphocytes in the presence of glucosamine.

Glucosamine is widely prescribed as a dietary supplement used to treat arthritis. In this study, the radioprotective ability of glucosamine was evaluated against radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Blood samples were collected from five healthy male donors and were divided into four groups. Isolated lymphocytes and blood samples were treated with 10 µM of glucosamine for 2 h before exposure to 2 Gy radiation. The radioprotective potential of glucosamine was assessed by micronucleus assay, reactive oxygen species (ROS) level analysis, and flow cytometry. Irradiation significantly increased the micronuclei frequency as compared to the control group. Contrary to that pretreatment with glucosamine before irradiation significantly reduced the frequency of micronuclei. Furthermore, pretreatment with glucosamine significantly prevented the percentage of apoptotic lymphocytes. Also, glucosamine pretreatment significantly reduced the production of ROS in irradiated lymphocytes. This study shows glucosamine to be a potent radioprotector against radiation that induces DNA damage and apoptosis in human lymphocytes. Several additional in vivo and in vitro studies are needed before glucosamine can be considered as a radioprotective candidate in patients undergoing radiation therapy.

Histopathological Evaluation of Protective Effect of Telmisartan against Radiation-Induced Bone Marrow Injury.

Background: Radiation-induced hematopoietic suppression and myelotoxicity can occur due to the nuclear accidents, occupational irradiation and therapeutic interventions. Bone marrow dysfunction has always been one of the most important causes of morbidity and mortality after ionizing irradiation. Objective: This study aims to investigate the protective effect of telmisartan against radiation-induced bone marrow injuries in a Balb/c mouse model. Material and Methods: In this experimental study, male Balb/c mice were divided into four groups as follow: group 1: mice received phosphate buffered saline (PBS) without irradiation, group 2: mice received a solution of telmisartan in PBS without irradiation, group 3: mice received PBS with irradiation, and group 4: mice received a solution of telmisartan in PBS with irradiation. A solution of telmisartan was prepared and administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. Protection of bone marrow against radiation induced damage was investigated by Hematoxylin-Eosin (HE) staining assay at 3, 9, 15 and 30 days after irradiation. Results: Histopathological analysis indicated that administration of telmisartan reduced X-radiation-induced damage and improved bone marrow histology. The number of different cell types in bone marrow, including polymorphonuclear /mononuclear cells and megakaryocytes significantly increased in telmisartan treated group compared to the only irradiated group at all-time points. Conclusion: The results of the present study demonstrated an efficient radioprotective effect of telmisartan in mouse bone marrow against sub-lethal X-irradiation.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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 60 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.

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

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.

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

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.