Modulation of Radiation-Induced NADPH Oxidases in Rat's Heart Tissues by Melatonin.

BACKGROUND: Experimental studies have shown that infiltration of inflammatory cells as well as upregulation of some cytokines play a central role in the development of late effects of ionizing radiation in heart tissues. Evidences have shown that an increased level of TGF-ß has a direct correlation with late effects of exposure to ionizing radiation such as chronic oxidative stress and fibrosis. Recent studies have shown that TGF-ß, through upregulation of pro-oxidant enzymes such as NOX2 and NOX4, promotes continuous ROS production and accumulation of fibrosis. OBJECTIVE: In present study, we aimed to evaluate the expression of NOX2 and NOX4 signaling pathways as well as possible modulatory effects of melatonin on the expression of these genes. MATERIAL AND METHODS: In this experimental study, four groups of 20 rats (5 in each) were used as follows; G1: control; G2: melatonin; G3: radiation; G4: radiation + melatonin. 100 mg/kg of melatonin was administrated before irradiation of heart tissues with 15 Gy gamma rays. 10 weeks after irradiation, heart tissues were collected for real-time Polymerase chain reaction (PCR). RESULTS: Results showed a significant increase in the expression of TGF-ß, Smad2, NF-kB, NOX2 and NOX4. The upregulation of NOX2 was more obvious by 20-fold compared to other genes. Except for TGF-ß, melatonin could attenuate the expression of other genes. CONCLUSION: This study indicated that exposure of rat's heart tissues to radiation leads to upregulation of TGF-ß-NOX4 and TGF-ß-NOX2 pathways. Melatonin, through modulation of these genes, may be able to alleviate radiation-induced chronic oxidative stress and subsequent consequences.

Efficacy and toxicity of FLASH radiotherapy: A systematic review.

In recent times, research on the use of ultrahigh-dose rates delivered in super-fast times in cancer treatment has been garnering interest. This has brought about the term "FLASH" radiotherapy (RT). Thus, in the present study, we systematically review these recent studies on FLASH RT with regard to its efficacy and safety. The reporting of this systematic review was done in line with the statement of Preferred Reporting Items for Systematic reviews and Meta-Analyses. Electronic search of the databases such as PubMed, Scopus, and Embase was conducted to retrieve relevant studies investigating the FLASH effect. From an initial search of 216 potential articles, 16 articles (in vivo, in vitro , and clinical studies) were finally included in this systematic review. Results showed that FLASH RT dose rates had protective effects on normal tissues in addition to antitumor effect. Although still in its early research stages, FLASH RT has the potential to rival present RT regimens in terms of safety and antitumor effect. However, further studies are needed to address the aspects such as optimal dose rate, effect on deep tumors, tumor recurrence, longer follow-up time, and mechanism of action.

Curcumin Protects Against Radiotherapy-Induced Oxidative Injury to the Skin.

OBJECTIVE: Side-effects to normal tissues reduce the therapeutic window of radiotherapy. During radiotherapy, the skin is inevitably exposed to doses of ionizing radiation, leading to varying degrees of skin damage. Natural antioxidants have been explored for their radioprotective potentials. Thus, the present study aimed to investigate the protective effect of curcumin against radiotherapy-induced oxidative damage to the skin. METHODS: Forty rats were divided into four groups as follows: vehicle control (without irradiation or drug treatment), treatment with 150 mg/kg curcumin, 10 Gy single dose irradiation only, and 150 mg/kg curcumin plus 10 Gy radiation (RC). In the treatment groups, each rat was treated orally with 150 mg/kg curcumin 1 day before irradiation to 3 consecutive days after irradiation. Weeks 1, 2, or 4 after irradiation, all rats were sacrificed and their skin tissues collected and frozen at -80°C for the determination of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity in skin tissues. RESULTS: Radiotherapy-induced oxidative injury to the skin was evidenced by elevated MDA levels as well as depleted CAT, SOD, and GSH-Px activities. However, the administration of curcumin before and after irradiation prevented radiotherapy-induced oxidative damage by significantly elevating the activities of antioxidant enzymes. CONCLUSION: From the findings of the present study, curcumin showed potential for protection against radiotherapy-induced oxidative injury to the skin. However, future studies are required to evaluate its clinical efficacy.

Radiation protection by Ex-RAD: a systematic review.

Protection of normal tissues against ionizing radiation-induced damages is a critical issue in clinical and environmental radiobiology. One of the ways of accomplishing radiation protection is through the use of radioprotectors. In the search for the most effective radioprotective agent, factors such as toxicity, effect on tumors, number of tissues protected, ease of administration, long-term stability, and compatibility with other drugs need to be assessed. Thus, in the present study, we systematically review existing studies on a chemical radioprotector, Ex-RAD, with the aim of examining its efficacy of radiation protection as well as underlying mechanisms. To this end, a systematic search of the electronic databases including Pubmed, Scopus, Embase, and Google Scholar was conducted to retrieve articles investigating the radioprotective effect of Ex-RAD. From an initial search of 268 articles, and after removal of duplicates as well as applying the predetermined inclusion and exclusion criteria, 10 articles were finally included for this systematic review. Findings from the reviewed studies indicated that Ex-RAD showed potentials for effective radioprotection of the studied organs with no side effect. Furthermore, the inhibition of apoptosis through p53 signaling pathway was the main mechanism of radioprotection by Ex-RAD. However, its radioprotective effect would need to be investigated for more organs in future studies.

Targets for protection and mitigation of radiation injury.

Protection of normal tissues against toxic effects of ionizing radiation is a critical issue in clinical and environmental radiobiology. Investigations in recent decades have suggested potential targets that are involved in the protection against radiation-induced damages to normal tissues and can be proposed for mitigation of radiation injury. Emerging evidences have been shown to be in contrast to an old dogma in radiation biology; a major amount of reactive oxygen species (ROS) production and cell toxicity occur during some hours to years after exposure to ionizing radiation. This can be attributed to upregulation of inflammatory and fibrosis mediators, epigenetic changes and disruption of the normal metabolism of oxygen. In the current review, we explain the cellular and molecular changes following exposure of normal tissues to ionizing radiation. Furthermore, we review potential targets that can be proposed for protection and mitigation of radiation toxicity.

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

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

Mitigation of Radiation-induced Pneumonitis and Lung Fibrosis using Alpha-lipoic Acid and Resveratrol.

BACKGROUND: Lung is a radiosensitive organ. Studies have shown that exposure of the lung to acute and high doses of radiation following inhalation of radioactive agents or an accidental radiological event may lead to pneumonitis and fibrosis, which are associated with a risk of death. So far, some agents have been studied for mitigation of pneumonitis and fibrosis following exposure of murine lung tissues to ionizing radiation. In this study, we aimed to detect the possible mitigatory effect of alpha-lipoic acid, resveratrol and their combination on mice pneumonitis and fibrosis markers following irradiation. METHODS: 25 mice were divided into 5 groups: control, radiation; radiation plus alpha-lipoic acid; radiation plus resveratrol; and radiation plus both resveratrol and alpha-lipoic acid. Mice chest regions were irradiated with 18 Gy using a cobalt-60 gamma rays source. Treatments started 24 h after irradiation and continued for two weeks. After 100 days, all mice were sacrificed and their lung tissues removed for histopathological evaluation. RESULTS: Pathological study showed that exposure to radiation led to severe pneumonitis and moderate fibrosis after 100 days. Both resveratrol and alpha-lipoic acid, as well as their combination could mitigate pneumonitis and fibrosis markers. Although, resveratrol could not mitigate infiltration of most inflammatory cells as well as inflammation and vascular damage, alpha-lipoic acid and its combination were able to mitigate most damaged markers. CONCLUSION: Alpha-lipoic acid and its combination with resveratrol were able to mitigate fibrosis and pneumonitis markers in mice lung tissues following lung irradiation. Although resveratrol has a protective effect on some markers, it has a weaker effect on lung injury. In conclusion, our results suggest that the combination of resveratrol and alpha-lipoic acid has a potent mitigatory effect compared to the single forms of these agents.

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.

Mitigation of Radiation-induced Gastrointestinal System Injury using Resveratrol or Alpha-lipoic Acid: A Pilot Histopathological Study.

AIM: In this study, we aimed to determine possible mitigation of radiationinduced toxicities in the duodenum, jejunum and colon using post-exposure treatment with resveratrol and alpha-lipoic acid. BACKGROUND: After the bone marrow, gastrointestinal system toxicity is the second critical cause of death following whole-body exposure to radiation. Its side effects reduce the quality of life of patients who have undergone radiotherapy. Resveratrol has an antioxidant effect and stimulates DNA damage responses (DDRs). Alpha-lipoic acid neutralizes free radicals via the recycling of ascorbic acid and alpha-tocopherol. OBJECTIVE: This study is a pilot investigation of the mitigation of enteritis using resveratrol and alpha-lipoic acid following histopathological study. METHODS: 60 male mice were randomly assigned to six groups; control, resveratrol treatment, alpha-lipoic acid treatment, whole-body irradiation, irradiation plus resveratrol, and irradiation plus alpha-lipoic acid. The mice were irradiated with a single dose of 7 Gy from a cobalt-60 gamma-ray source. Treatment with resveratrol or alpha-lipoic acid started 24 h after irradiation and continued for 4 weeks. All mice were sacrificed after 30 days for histopathological evaluation of radiation-induced toxicities in the duodenum, jejunum and colon. RESULTS AND DISCUSSION: Exposure to radiation caused mild to severe damages to vessels, goblet cells and villous. It also led to significant infiltration of macrophages and leukocytes, especially in the colon. Both resveratrol and alpha-lipoic acid were able to mitigate morphological changes. However, they could not mitigate vascular injury. CONCLUSION: Resveratrol and alpha-lipoic acid could mitigate radiation-induced injuries in the small and large intestine. A comparison between these agents showed that resveratrol may be a more effective mitigator compared to alpha-lipoic acid.

Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization.

Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.

Protective Effect of Metformin, Resveratrol and Alpha-lipoic Acid on Radiation- Induced Pneumonitis and Fibrosis: A Histopathological Study.

BACKGROUND: Radiation-induced pneumonitis and fibrosis are the most common side effects of chest radiotherapy. They result from massive and chronic production of Reactive Oxygen Species (ROS), inhibition of antioxidant enzymes as well as the release of several inflammatory mediators. In this study, we aimed to detect the radioprotective effects of metformin (as inhibitor of mitochondrial ROS), resveratrol (as stimulator of antioxidant defense enzymes) and alpha-lipoic acid (as direct antioxidant) for alleviating radiation-induced pneumonitis and fibrosis. METHODS: 80 Male Mice were randomly allotted to eight groups which include G1: control; G2: resveratrol; G3: alpha-lipoic acid; G4: metformin; G5: radiation; G6: radiation plus resveratrol; G7: radiation plus alpha-lipoic acid; G8: radiation plus metformin. Drugs' doses were as follows: 100 mg/kg metformin, 200 mg/kg resveratrol and 200 mg/kg alpha-lipoic acid. Irradiation with a single radiation dose of 18 Gy was performed using a cobalt-60 (60Co) gamma-ray source. After 80 days, all mice were sacrificed and their lung tissues evaluated for morphological changes using histopathological markers. RESULTS: Irradiation led to acute pneumonitis including infiltration of inflammatory cells and damages to alveolar and vascular, as well as mild fibrosis. Metformin, alpha-lipoic acid and resveratrol were able to reduce pneumonitis and overcome radiation-induced fibrosis. CONCLUSION: All agents could protect against radiation-induced lung injury moderately. It is possible that administering higher doses of these drugs over a long period of time could give better radioprotection of the lung.

Boosting immune system against cancer by melatonin: A mechanistic viewpoint.

Cancer is a disease of high complexity. Resistance to therapy is a major challenge in cancer targeted therapies. Overcoming this resistance requires a deep knowledge of the cellular interactions within tumor. Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are the main anti-cancer immune cells, while T regulatory cells (Tregs) and cancer associated fibroblasts (CAFs) facilitate immune escape of cancer cells. Melatonin is a natural agent with anti-cancer functions that has also been suggested as an adjuvant in combination with cancer therapy modalities such as chemotherapy, radiotherapy, immunotherapy and tumor vaccination. One of the main effects of melatonin is regulation of immune responses against cancer cells. Melatonin has been shown to potentiate the activities of anti-cancer immune cells, as well as attenuating the activities of Tregs and CAFs. It also has a potent effect on the mitochondria, which may change immune responses against cancer. In this review, we explain the mechanisms of immune regulation by melatonin involved in its anti-cancer effects.

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.

Genomic Instability and Carcinogenesis of Heavy Charged Particles Radiation: Clinical and Environmental Implications.

One of the uses of ionizing radiation is in cancer treatment. The use of heavy charged particles for treatment has been introduced in recent decades because of their priority for deposition of radiation energy in the tumor, via the Bragg peak phenomenon. In addition to medical implications, exposure to heavy charged particles is a crucial issue for environmental and space radiobiology. Ionizing radiation is one of the most powerful clastogenic and carcinogenic agents. Studies have shown that although both low and high linear energy transfer (LET) radiations are carcinogenic, their risks are different. Molecular studies have also shown that although heavy charged particles mainly induce DNA damage directly, they may be more potent inducer of endogenous generation of free radicals compared to the low LET gamma or X-rays. It seems that the severity of genotoxicity for non-irradiated bystander cells is potentiated as the quality of radiation increases. However, this is not true in all situations. Evidence suggests the involvement of some mechanisms such as upregulation of pro-oxidant enzymes and change in the methylation of DNA in the development of genomic instability and carcinogenesis. This review aimed to report important issues for genotoxicity of carcinogenic effects of heavy charged particles. Furthermore, we tried to explain some mechanisms that may be involved in cancer development following exposure to heavy charged particles.

Targets for improving tumor response to radiotherapy.

Radiotherapy is one of the most common treatment modalities for controlling a wide range of tumors. However, it has been shown that radiotherapy alone is unable to completely eradicate some tumors and could be associated with a high possibility of tumor recurrence. To date, various experimental and clinical studies have been conducted to explore some efficient targets within tumor microenvironment (TME) to enhance tumor response to radiotherapy; thus help eliminate or eradicate tumors. Although targeting DNA damage responses (DDRs) is associated with severe toxicities, studies in recent decade suggest that inhibition of some apoptosis/survival targets within TME is promising. This is also associated with changes in the numbers of T regulatory cells (Tregs) and cytotoxic T lymphocytes (CTLs). The inhibition of cyclooxygenase-2 (COX-2), phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs) and vascular endothelial growth factor (VEGF) have also shown promising results. The combination of receptor tyrosine kinase (RTK) inhibitors with radiotherapy is interesting as well as the clinical use of some drugs and antibodies. Epidermal growth factor receptor (EGFR) inhibitors are the most common RTK inhibitors. Some clinical trials in recent years have shown very interesting results for immune checkpoint inhibitors (ICIs), especially programmed death-ligand 1 (PD-L1) and CTLs-associated antigen 4 (CTLA-4) inhibitors. It has been suggested that administration of ICIs during or after hypofractionated radiotherapy could lead to best results. In this review, we explain TME response to radiotherapy and potential targets for sensitization of cancer cells to radiotherapy.

Histopathological and Functional Evaluation of Radiation-Induced Sciatic Nerve Damage: Melatonin as Radioprotector.

Background and Objectives: Radiotherapy uses ionizing radiation for cancer treatment. One of the side effects of radiotherapy is peripheral neuropathy. After irradiation, the first stage of neuropathy involves electrophysiological, biochemical and histopathological variations, while the fibrosis of soft tissues surrounding the exposed nerve occurs in the second stage. The present study aimed to examine the radioprotective effects of melatonin against ionizing radiation-induced sciatic nerve damage. Materials and Methods: Sixty male Wistar rats were assigned to four groups: C (Control + Vehicle), M (Melatonin), R (Radiation + Vehicle), MR (Radiation + Melatonin). Their right legs were irradiated with a 30 Gy single dose of gamma rays. Then, 100 mg/kg melatonin was administered to the animals 30 min before irradiation once daily (5 mg/kg) until the day of rats' sacrifice. Their exposed nerve tissues were assessed using the sciatic functional index (SFI) and histological evaluation. Results: Four, 12 and 20 weeks post irradiation, the SFI results showed that irradiation led to partial loss of motor nerve function after 12 and 20 weeks. Histological evaluation showed the various stages of axonal degeneration and demyelination compared to the C and M groups. Scar-like tissues were detected around the irradiated nerves in the R group at 20 weeks, but were absent in the MR group. The SFI and histological results of the R group showed partial nerve lesion. However, in all cases, treatment with melatonin prevented these effects. Conclusions: Results showed that melatonin has the potential to improve functional and morphological features of exposed sciatic nerves. This could possibly improve the therapeutic window of radiotherapy.

Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study.

Background and objectives: Pneumonitis and fibrosis are the most common consequences of lung exposure to a high dose of ionizing radiation during an accidental radiological or nuclear event, and may lead to death, after some months to years. So far, some anti-inflammatory and antioxidant agents have been used for mitigation of lung injury. In the present study, we aimed to detect possible mitigatory effects of melatonin and metformin on radiation-induced pneumonitis and lung fibrosis. Materials and methods: 40 male mice were divided into 4 groups (10 mice in each). For control group, mice did not receive radiation or drugs. In group 2, mice were irradiated to chest area with 18 Gy gamma rays. In groups 3 and 4, mice were first irradiated similar to group 2. After 24 h, treatment with melatonin as well as metformin began. Mice were sacrificed after 100 days for determination of mitigation of lung pneumonitis and fibrosis by melatonin or metformin. Results: Results showed that both melatonin and metformin are able to mitigate pneumonitis and fibrosis markers such as infiltration of inflammatory cells, edema, vascular and alveolar thickening, as well as collagen deposition. Conclusion: Melatonin and metformin may have some interesting properties for mitigation of radiation pneumonitis and fibrosis after an accidental radiation event.

Selenium-L-methionine modulates radiation injury and Duox1 and Duox2 upregulation in rat's heart tissues.

Introduction: Redox interactions play a key role in radiation injury including heart diseases. In present study, we aimed to detect the possible protective role of selenium-L-methionine on infiltration of immune cells and Duox1&2 upregulation in rat's heart tissues. Methods: In this study, 20 rats were divided into 4 groups (5 rats in each) namely: irradiation; irradiation plus Selenium-L-methionine; control; and Selenium-L-methionine treatment. Irradiation (15 Gy to chest) was performed using a cobalt-60 gamma ray source while 4 mg/kg of selenium-L-methionine was administered intraperitoneally. Ten weeks after irradiation, rats were sacrificed for detection of IL-4 and IL-13 cytokines, infiltration of macrophages and lymphocytes as well as the expressions of IL4Ra1, Duox1, IL13Ra2 and Duox2. Results: Results showed an increase in the level of IL-4 as well as the expressions of IL4Ra1, Duox1 and Duox2. Similarly, there was an increase in the infiltration of lymphocytes and macrophages. There was significant attenuation of all these changes following treatment with selenium-L-methionine. Conclusion: Selenium-L-methionine has the potential to protect heart tissues against radiation injury. Downregulation of pro-oxidant genes and modulation of some cytokines such as IL-4 are involved in the radioprotective effect of selenium-L-methionine on heart tissues.

Radioprotective Effect of Hesperidin: A Systematic Review.

Background and objectives: Ionizing radiation (IR) has been of immense benefit to man, especially for medical purposes (diagnostic imaging and radiotherapy). However, the risks of toxicity in healthy normal cells, leading to cellular damage as well as early and late side effects, have been major drawbacks. The aim of this study was to evaluate the radioprotective effect of hesperidin against IR-induced damage. Materials and Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) were applied in reporting this study. A search was conducted using the electronic databases PubMed, Scopus, Embase, Google Scholar, and www.ClinicalTrials.gov for information about completed or ongoing clinical trials. Results: From our search results, 24 studies involving rats, mice, and cultured human and animal cells were included. An experimental case-control design was used in all studies. The studies showed that the administration of hesperidin reduced oxidative stress and inflammation in all investigated tissues. Furthermore, it increased 30-day and 60-day survival rates and protected against DNA damage. The best radioprotection was obtained when hesperidin was administered before irradiation. Conclusions: The results of the included studies support the antioxidant, anti-inflammatory, and antiapoptotic abilities of hesperidin as a potential radioprotective agent against IR-induced damage. We recommend future clinical trials for more insights.

Protective Effect of Melatonin Against Radiotherapy-Induced Small Intestinal Oxidative Stress: Biochemical Evaluation.

Background and Objectives: Radiation enteritis is a common side effect after radiotherapy for abdominal and pelvic malignancies. The aim of the present study was to investigate the protective effect of melatonin, known for its free radical scavenging ability, against radiotherapy-induced small intestinal oxidative damage. Materials and Methods: Thirty male Wistar rats were randomly assigned to six groups (5 rats in each) as follows: Group I (control group) rats received neither radiation nor melatonin; group II rats received only 8 Gy single dose of gamma radiation to their abdomen and pelvis regions; group III (administered with only 50 mg/kg melatonin); group IV (administered with only 100 mg/kg melatonin); group V (50 mg/kg melatonin + 8 Gy radiation), group VI (100 mg/kg melatonin + 8 Gy radiation). All rats were sacrificed after 5 days for biochemical assessments of their intestinal tissues. Results: Treatment with melatonin post irradiation significantly reduced malondialdehyde (MDA) levels as well as increased both superoxide dismutase (SOD) and catalase (CAT) activities of the irradiated intestinal tissues. In addition, melatonin administration with different doses pre irradiation led to protection of the tissues. Moreover, the 100 mg/kg dose was more effective compared to 50 mg/kg. Conclusions: The results of our study suggest that melatonin has a potent protective effect against radiotherapy-induced intestinal damage, by decreasing oxidative stress and increasing antioxidant enzymes. We recommend future clinical trials for more insights.