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

ปัจจัยที่สัมพันธ์กับความรุนแรงในที่ทำงานของพยาบาลประเทศภูฏาน Factors Related to Workplace Violence as Perceived by Nurses in Bhutan

บทคัดย่อ วัตถุประสงค์: เพื่อศึกษาผลกระทบและปัจจัยที่สัมพันธ์กับความรุนแรงในที่ทำงานของพยาบาล ประเทศภูฏาน วิธีการศึกษา: กลุ่มตัวอย่างเป็นพยาบาลที่ปฏิบัติงานที่โรงพยาบาลระดับตติยภูมิจำนวน 190 ราย เครื่องมือวิจัยประกอบด้วยแบบบันทึกข้อมูล แบบสำรวจความรุนแรงในที่ทำงานของพยาบาลวิชาชีพ แบบสอบถามสิ่งแวดล้อมที่ทำงาน แบบสอบถามบุคคลิกภาพ แบบสอบถามสมรรถนะของพยาบาล และแบบเอกสิทธิ์เชิงวิชาชีพ สถิติวิเคราะห์ข้อมูลประกอบด้วยสถิติพรรณา ไคสแควร์ และสหสัมพันธ์พ้อยท์ไบซีเรียล ผลการศึกษา: ปัจจัยด้านหอผู้ป่วย สมรรถนะและภาระงานของพยาบาลมีความสัมพันธ์กับความรุนแรงในที่ทำงานของพยาบาลอย่างมีนัยสำคัญทางสถิติที่ระดับ 0.05 สรุป: การลดความรุนแรงในที่ทำงานของพยาบาล ผู้บริหารทางการพยาบาลหรือผู้ออกแบบนโยบายควรพัฒนาสมรรถนะและจัดภาระงานให้เหมาะสมกับลักษณะผู้ป่วยและควรคำนึงถึงการจัดสภาพหอผู้ป่วย คำสำคัญ: ความรุนแรงในที่ทำงาน, พยาบาล, ประเทศภูฏานAbstract Objective: To investigate the impact and factors related to workplace violence as perceived by nurses working in Bhutan. Method: Data were collected using sets of self-reported questionnaires consisting of workplace violence survey, Short Version of Nursing Professional Competency Scale, Practice Work Environment–Nursing Work Index Scale, Revised Eysenck Personality Questionnaire short scale, Autonomy and Control scale and Workload Perception Questionnaire. Descriptive statistics, chi-square testand point biserial test were used for data analysis. Results: It was found that  current work unit, nursing competency and workload perception had significant relationships with workplace violence (P-value < 0.05). Conclusion: In order to minimize workplace violence against nurses, nurse administrators and concerned policy makers should improve nursing competency and balance nursing workload under work unit condition. Keywords: workplace violence, nurses, Bhuta

Reduction–oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics

Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems

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.

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. © 2018 Bentham Science Publishers

Targeting of inflammation for radiation protection and mitigation

Background: Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Discussion: Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect. Inflammation in both irradiated and non-irradiated cells can trigger genomic instability, leading to increased risk of carcinogenesis. Targeting the inflammatory mediators has been an interesting idea for improving the therapeutic ratio throughout the reduction of normal tissue injury as well as an increase in tumor response to radiotherapy. Conclusion: So far, various targets have been proposed for the amelioration of radiation toxicity in radiotherapy. Of different targets, NF-κB, COX-2, some of NADPH Oxidase subfamilies, TGF-β, p38 and the renin-angiotensin system have shown promising results. Interestingly, inhibition of these targets can help sensitize the tumor cells to the radiation treatment with some mechanisms such as suppression of angiogenesis and tumor growth as well as induction of apoptosis. In this review, we focus on recent advances on promising studies for targeting the inflammatory mediators in radiotherapy. © 2018 Bentham Science Publishers

COX-2 in radiotherapy: A potential target for radioprotection and radiosensitization

Background: Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Discussion: Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the activation of this enzyme can increase resistance of malignant cells to radiotherapy. Hence, the inhibition of COX-2 has been proposed for better therapeutic response and amelioration of normal tissues. Celecoxib is one of the most studied COX-2 inhibitor for radiosensitization and radioprotection, while some other inhibitors have shown interesting results. Conclusion: In this review, we describe the role of COX-2 in radiation normal tissue injury as well as irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2 induced tumor resistance to radiotherapy and the potential role of COX-2 inhibition are discussed. © 2018 Bentham Science Publishers

Radiation-induced inflammation and autoimmune diseases

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

Radiation-induced inflammation and autoimmune diseases

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

Radiation-induced inflammation and autoimmune diseases

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