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 60Co 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. Key words: Radiation, Spermatogenesis, Resveratrol, Alpha-Lipoic Acid, Coenzyme Q10

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. Key words: Radiation, Testis, Leydig cells, Melatonin, Metformin, Spermatogenesis

Evaluating the Protective Effect of a Combination of Curcumin and Selenium-L-Methionine on Radiation Induced Dual Oxidase Upregulation

Background: Epidemiological studies have shown an increased incidence of heart diseases among survivors of Chernobyl disaster as well as Hiroshima and Nagasaki atomic bomb explosion. Similar results were observed for lung and left breast cancer patients. Experimental studies have proposed the chronic upregulation of some pro-inflammatory and pro-fibrotic cytokines. Recent studies have shown that upregulation of pro-oxidant enzymes play a key role in the development of late effects of ionizing radiation such as fibrosis. Interleukin-4 (IL-4) and Interleukin-13 (IL-13) are two important cytokines that have shown ability to induce production of free radicals through dual oxidases (Duox) i.e. Duox1 and Duox2. In this study, we aimed to detect the expression of IL-4 receptor-a1 (IL-4Ra1), IL-13 receptor-a2 (IL-13Ra2), Duox1 and Duox2 genes following irradiation of rat’s heart. In addition, we evaluated the possible role of the combination of curcumin and selenium-L-methionine on the regulation of these genes. Methods: Twenty rats were divided into 4 groups as follows; G1: control; G2: treatment with the combination of curcumin and selenium-L-methionine; G3: radiation; G4: radiation plus treatment with the combination of curcumin and selenium-L-methionine. Rats were sacrificed 10 weeks after irradiation for detecting the expression of IL-4Ra1, IL-13Ra2, Duox1 and Duox2. Results: Results showed that exposure to ionizing radiation caused upregulation of IL-4Ra1 by more than 4-fold as well as Duox1 and Duox2 by more than 5-fold. However, results showed no detectable expression for IL-13Ra2. Treatment with the combination of curcumin and selenium-L-methionine could attenuate the upregulation of all genes. Conclusion: This study has shown that exposing rat’s heart tissues to radiation leads to chronic upregulation of IL-4Ra1, Duox1 and Duox2 as well as pro-oxidant enzymes. Treatment with the combination of curcumin and selenium-L-methionine showed ability to attenuate the upregulation of these genes

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

Purpose: Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat’s lung tissues. Methods: 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4–DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR

Radiation-Induced Heart Diseases: Protective Effects of Natural Products

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

Immigration et crise d’identite dans l’Univers Romanesque de Sami Tchak

La littérature africaine du XXIème siècle a eu une grande transformation. Cela est dû au fait qu’on voit paraître sur la scène littéraire un assez bon nombre de jeunes écrivains et écrivaines de la postindépendance qui de gré ou de force s’installent en Occident et exercent leur métier d’écrivain en  situation d’immigrés ou d’exilés. Il ne s’agit plus de la négritude mais d’un nouveau courant ou mouvement littéraire que Chevrier a nommé la migritude. Les ouvrages de ces écrivains de la migritude se caractérisent fortement par l’immigration et la crise d’identité entre autres. Ces deux thèmes attirent notre attention dans la présente étude qui a à sa disposition les approches descriptive et psychanalytique. L’objectif de cette étude est la mise en évidence de la thématique aussi bien de l’immigration que de la crise identitaire. Pour ce faire, cinq romans de Sami Tchak constituent notre corpus de base. Ils sont examinés à fond pour démontrer comment le jeune romancier togolais a abordé le sujet en question. Il a été constaté que Sami Tchak se préoccupe profondément de la thématique aussi bien de l’immigration que de la crise identitaire dans son univers romanesque.English AbstractAfrican literature in the twenty-first century has undergone great transformation. This is because appearing on the literary scene is a large number of young writers of the post independence era ,who of their own volition or by force, settle in the western world and carry on with their work as writers in their situation as immigrants and exiles. It is no more the issue of negritude but of a new literary movement which Chevrier named migritude. The works of these migritude writers are strongly characterized by immigration and identity crises among others. The present study which makes use of descriptive and psychoanalytical approaches takes interest in these two themes. The objective of the study is to examine the themes of immigration and identity crisis. For our corpus, we have five novels of Sami Tchak. They are examined thoroughly to bring out the young Togolese novelist’s treatment of the subject in question. It is established that Sami Tchak takes profound interest in projecting and handling the themes of immigration and identity crisis in his novelistic world

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

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

Role of tumor microenvironment in cancer stem cells resistance to radiotherapy

Cancer is a chronic disorder that involves several elements of both the tumor and the host stromal cells. At present, the complex relationship between the various factors presents in the tumor microenvironment (TME) and tumor cells, as well as immune cells located within the TME, is still poorly known. Within the TME, the crosstalk of these factors and immune cells essentially determines how a tumor reacts to the treatment and how the tumor can ultimately be destroyed, re-main dormant, or develop and metastasize. Also, in TME, reciprocal crosstalk between cancer-asso-ciated fibroblasts (CAFs), extracellular matrix (ECM), hypoxia-inducible factor (HIF) intensifies the proliferation capacity of cancer stem cells (CSCs). CSCs are a subpopulation of cells that reside within the tumor bulk and have the capacity to self-renew, differentiate, and repair DNA damage. These characteristics make CSCs develop resistance to a variety of treatments, such as radiotherapy (RT). RT is a frequent and often curative treatment for local cancer which mediates tumor elimi-nation by cytotoxic actions. Also, cytokines and growth factors that are released into TME have been involved in the activation of tumor radioresistance and the induction of different immune cells, altering local immune responses. In this review, we discuss the pivotal role of TME in the resistance of CSCs to RT