RESUMO
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.
Assuntos
Lesões por Radiação/metabolismo , Lesões por Radiação/prevenção & controle , Animais , Epigênese Genética/fisiologia , Humanos , Estresse Oxidativo/fisiologia , Radiação Ionizante , Espécies Reativas de Oxigênio/metabolismoRESUMO
Radiotherapy and chemotherapy are two famous modalities in tumor-targeted therapy that lead to systemic and local toxicities for normal tissues. Moreover, several studies have confirmed that exposure of the tumor to radiation or chemotherapy drugs stimulate some signaling pathways in the tumor microenvironment (TME), leading to resistance of cancer cells to apoptosis, as well as promoting angiogenesis and tumor growth. Nuclear factor kappa B (NF-κB) plays a central role in the regulation of inflammatory responses in both normal tissues and tumors via the release of several cytokines, regulation of prostaglandins, reduction/oxidation (redox) reactions, angiogenesis, and cell death. Upregulation of NF-κB in normal tissues causes an appearance of inflammatory reactions and oxidative stress, whereas it regulates angiogenesis and suppresses apoptosis, leading to resistance to subsequent doses of radiation or chemotherapy. Selective inhibition of NF-κB in experimental studies has shown promising results for tumor sensitization via apoptosis induction, inhibition of angiogenesis, and increasing delay of tumor growth. The use of some agents for NF-κB inhibition has been shown to alleviate radiation/chemotherapy toxicities in normal cells/ tissues. In this current review, we explained the pivotal role of NF-κB in both normal tissue toxicity and tumor resistance. We also discussed the promising strategies for overcoming these problems with regard to chemotherapy and radiotherapy.
Assuntos
Resistencia a Medicamentos Antineoplásicos/fisiologia , NF-kappa B/metabolismo , Neoplasias/metabolismo , Tolerância a Radiação/fisiologia , Animais , HumanosRESUMO
Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.
Assuntos
Antioxidantes/administração & dosagem , Neoplasias/radioterapia , Lesões por Radiação/prevenção & controle , Selênio/administração & dosagem , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Oxirredução/efeitos dos fármacos , Lesões por Radiação/etiologia , Tolerância a Radiação/efeitos dos fármacos , Protetores contra Radiação/administração & dosagem , Radioterapia/efeitos adversos , Selênio/metabolismoRESUMO
Cardiovascular diseases (CVDs) account for the majority of deaths worldwide. Radiation-induced heart diseases (RIHD) is one of the side effects following exposure to ionizing radiation (IR). Exposure could be from various forms such as diagnostic imaging, radiotherapy for cancer treatment, as well as nuclear disasters and nuclear accidents. RIHD is mostly observed after radiotherapy for thoracic malignancies, especially left breast cancer. RIHD may affect the supply of blood to heart muscles, leading to an increase in the risk of heart attacks to irradiated persons. Due to its dose-limiting consequence, RIHD has a negative effect on the therapeutic efficacy of radiotherapy. Several methods have been proposed for protection against RIHD. In this paper, we review the use of natural products, which have shown promising results for protection against RIHD.
Assuntos
Produtos Biológicos/uso terapêutico , Cardiopatias/etiologia , Fatores de Proteção , Lesões por Radiação/complicações , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/uso terapêutico , Curcumina/farmacologia , Curcumina/uso terapêutico , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Guaiacol/análogos & derivados , Guaiacol/farmacologia , Guaiacol/uso terapêutico , Cardiopatias/fisiopatologia , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Humanos , Melatonina/farmacologia , Melatonina/uso terapêutico , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Álcool Feniletílico/uso terapêutico , Lesões por Radiação/fisiopatologia , Selênio/farmacologia , Selênio/uso terapêutico , VitisRESUMO
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.
Assuntos
Hesperidina/efeitos da radiação , Radiação Ionizante , Animais , Antioxidantes/efeitos da radiação , Antioxidantes/uso terapêutico , Humanos , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , RatosRESUMO
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.
Assuntos
Intestino Delgado/efeitos da radiação , Melatonina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Radioterapia/efeitos adversos , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Intestino Delgado/fisiopatologia , Masculino , Melatonina/uso terapêutico , Lesões por Radiação/complicações , Lesões por Radiação/prevenção & controle , Radioterapia/métodos , Ratos , Ratos WistarRESUMO
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.
Assuntos
Antioxidantes/uso terapêutico , Melatonina/uso terapêutico , Lesões Experimentais por Radiação , Neuropatia Ciática , Animais , Modelos Animais de Doenças , Masculino , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controle , Ratos , Ratos Wistar , Neuropatia Ciática/patologia , Neuropatia Ciática/prevenção & controleRESUMO
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.
Assuntos
Dano ao DNA/genética , Neoplasias/radioterapia , Radiação Ionizante , Relação Dose-Resposta à Radiação , Instabilidade Genômica , HumanosRESUMO
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.
Assuntos
Melatonina/uso terapêutico , Metformina/uso terapêutico , Pneumonite por Radiação/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Melatonina/metabolismo , Metformina/metabolismo , Camundongos , Substâncias Protetoras/metabolismo , Substâncias Protetoras/uso terapêutico , Exposição à Radiação/efeitos adversos , Exposição à Radiação/estatística & dados numéricos , Pneumonite por Radiação/patologiaRESUMO
Background: Radiation-induced heart injury can lead to increased risk of heart failure, attack, and ischemia. Some studies proposed IL-4 and IL-13 as two important cytokines that are involved in late effects of ionizing radiation. On the other hand, these cytokines may, through upregulation of Duox1 and Duox2, induce chronic oxidative stress, inflammation, and fibrosis. In this study, we evaluated the upregulation of Duox1 and Duox2 pathways in hearts following chest irradiation in rats and then detected possible attenuation of them by melatonin. Materials and Methods: Twenty male Wistar rats were divided into four groups: (1) control; (2) melatonin treated (100 mg/kg); (3) radiation (15 Gy gamma rays); (4) melatonin treated before irradiation. All rats were sacrificed after 10 weeks and their heart tissues collected for real-time PCR (RT-PCR), ELISA detection of IL-4 and IL-13, as well as histopathological evaluation of macrophages and lymphocytes infiltration. Results: Results showed an upregulation of IL-4, IL4ra1, Duox1, and Duox2. The biggest changes were for IL4ra1 and Duox1. Treatment with melatonin before irradiation could attenuate the upregulation of all genes. Melatonin also caused a reduction in IL-4 as well as reverse infiltration of inflammatory cells. Conclusion: Duox1 and Duox2 may be involved in the late effects of radiation-induced heart injury. Also, via attenuation of these genes, melatonin can offer protection against the toxic effects of radiation on the heart.
Assuntos
Oxidases Duais/efeitos da radiação , Melatonina/farmacologia , Regulação para Cima/efeitos da radiação , Análise de Variância , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Cardiopatias Congênitas , Masculino , Melatonina/uso terapêutico , Fatores de Proteção , Lesões por Radiação , Ratos , Ratos Wistar , Regulação para Cima/fisiologiaRESUMO
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.
RESUMO
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.
Assuntos
Neoplasias/radioterapia , Tratamentos com Preservação do Órgão/métodos , Radioterapia (Especialidade)/normas , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Neoplasias/patologia , Tolerância a Radiação , Radioterapia/efeitos adversos , Radioterapia/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/normas , Resultado do TratamentoRESUMO
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.
Assuntos
Colo/patologia , Enterite/tratamento farmacológico , Íleo/patologia , Melatonina/uso terapêutico , Metformina/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Animais , Colo/efeitos dos fármacos , Colo/efeitos da radiação , Quimioterapia Combinada , Enterite/patologia , Humanos , Íleo/efeitos dos fármacos , Íleo/efeitos da radiação , Masculino , Modelos Animais , Lesões por Radiação/patologia , Ratos , Ratos Wistar , Irradiação Corporal TotalRESUMO
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.
Assuntos
Neoplasias/tratamento farmacológico , Resveratrol/farmacologia , Animais , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Resistencia a Medicamentos Antineoplásicos , Humanos , Terapia de Alvo Molecular , Neoplasias/radioterapia , Estresse Oxidativo/efeitos da radiação , Protetores contra Radiação/farmacologiaRESUMO
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.
Assuntos
Proteção Radiológica , Protetores contra Radiação , Radiação Ionizante , SulfonamidasRESUMO
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.
Assuntos
Curcumina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Lesões por Radiação/tratamento farmacológico , Protetores contra Radiação/farmacologia , Pele/efeitos dos fármacos , Administração Oral , Animais , Curcumina/administração & dosagem , Raios gama , Masculino , Protetores contra Radiação/administração & dosagem , Ratos , Ratos WistarRESUMO
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.
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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.
Assuntos
Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/uso terapêutico , Resveratrol/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Colo/efeitos dos fármacos , Colo/patologia , Colo/efeitos da radiação , Duodeno/efeitos dos fármacos , Duodeno/patologia , Duodeno/efeitos da radiação , Raios gama/efeitos adversos , Jejuno/efeitos dos fármacos , Jejuno/patologia , Jejuno/efeitos da radiação , Masculino , Camundongos , Lesões Experimentais por Radiação/patologia , Irradiação Corporal Total/efeitos adversosRESUMO
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.
Assuntos
Antioxidantes/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Pneumonite por Radiação/tratamento farmacológico , Resveratrol/uso terapêutico , Ácido Tióctico/uso terapêutico , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Humanos , Camundongos , RadiaçãoRESUMO
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.