Research progress of irradiation injuries anti-agents / 中华劳动卫生职业病杂志

Irradiation injuries anti-agents refer to drugs that can inhibit the initial stage of radiation injuries, or reduce the development of radiation injuries and promote the recovery of injuries when used early after irradiation exposure. According to the mechanism of action and the time of intervention, the irradiation injuries anti-agents are divided into four categories: radioprotectors, radiomitigators, radiation therapeutics for external radiation exposure, and anti-agents for internalized radionuclides. In this paper, the research progress of irradiation injuries anti-agents in recent years is reviewed.

The probable radioprotective role of Acacia nilotica L. against biochemical and cytogenetic disorders induced in gamma irradiated male rats

Gum Arabic (Acacia nilotica L.) is a respected plant that has many nutrients and curative practices. It hinders, improves, or manages many disorders. The radio-protective activity of Acacia nilotica was investigated against γ-rays-induced testicle damage in rats. Twenty-four rats were correspondingly distributed into 4 groups; control, Acacia nilotica (15mg/kg, daily for 30 days), γ-irradiated (5Gy γ-rays, single dose) and Acacia nilotica plus γ-rays treated groups. The plasma testosterone and total antioxidant status (TAS) were estimated. Lipid peroxidation; malondialdehyde (MDA), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), also glutathione peroxidase (GPx), catalase (CAT), tumor necrosis factor-α (TNF-α) with interleukin-1ß (IL-1ß), were determined in the testicle tissues. A testis weight, sperm count and motility, peripheral-blood and bone-marrow micronuclei (PMN and BMN), and frequency of chromosomal aberrations (CAs) were scored. A significant decline in the levels of plasma testosterone with TAS observed in the γ-irradiated rats. The results also showed significantly increased levels of testicle MDA, inflammatory markers, PMN, BMN and CAs frequencies and decrease in testes weight, sperm count and motility and levels of testicle antioxidants markers in gamma irradiated group. All these biochemical and fertility indices results were significantly enhanced in the Acacia nilotica plus γ-rays treated groups. However, the possible alleviate activity of Acacia nilotica on γ-rays-induced testicle injury in rats has not previously conversed, and this is the topic of this study.

Radioprotective Effect of Nigella Sativa Oil on Heart Tissues of Rats Exposed to Irradition

Abstract Background Various studies are ongoing related to the radioprotective agents. Herbal preparations are currently becoming popular because of their beneficial effects with fewer side effects compared to the synthetic/semi-synthetic medicines, and Nigella sativa oil (NSO) is only one of them. Objective To investigate NSO for its antioxidant effects on the heart tissue of rats exposed to ionizing radiation (IR). Methods Thirty six male albino Wistar rats, divided into four groups, were designated to group I (IR plus NSO group) that received both 5 Gray of gamma IR to total cranium and NSO; group II (IR alone group) that received IR plus saline, group III (control group of NSO) that received saline and did not receive NSO or IR; group IV (control group) that received only sham IR. Alterations in Total antioxidant status (TAS) and Total oxidant status (TOS), Oxidative stres index (OSI), Sulhydryl group (SH), Lipid hydroperoxide (LOOH), Paraoxonase (PON) levels, Arylesterase (ARE) and Ceruloplasmin (CER) activities in homogenized heart tissue of rats were measured by biochemical methods. Results In heart tissue of the rats in the IR alone group (group II) LOOH, TOS and OSI levels were found to be higher, ARE activity and TAS level were found to be lower than all of the other groups (p < 0.01). These results also support that IR increases oxidative stress and NSO's protective effect. Conclusion NSO would reduce the oxidative damage in the irradiated heart tissue in the experimental rat model.

Efecto radioprotector del ácido tánico y vinos de la var vitis vinífera L. cv tannat en Saccharomyces cerevisiae / Radioprotective effect of tannic acid and wines of the vitis vinifera L. cv tannat on Saccharomyces cerevisiae / Proteção contra radiação por vinho tinto var tannat e ácido tanico em Saccharomyces cerevisiae

El vino tinto variedad Vitis vinifera L. cv Tannat en los últimos años ha tomado relevancia por su alta concentración de polifenoles, esto le podría significar un rol protector sobre el genoma disminuyendo la formación de lesiones oxidativas. Los efectos a nivel celular de las radiaciones ionizantes en blancos como el ADN, componentes de cascadas de transducción de señales, resultan en lesiones letales, mutagénicas y recombinogénicas y en retardos en el ciclo celular. Se utilizó como modelo eucariota poblaciones de Saccharomyces cerevisiae en fase exponencial expuestas a radiación gamma (200 Gy) en presencia, o ausencia, de vino Tannat (10 % v/v) o de ácido tánico (60 µg/mL). Se estimaron las probabilidades de sobrevida y frecuencia mutagénica en distintas condiciones. Las muestras celulares expuestas a radiación ionizante presentaron una fracción de sobrevida de 0.21 ± 0.02 mientras que en las muestras irradiadas en presencia de vino Tannat o de ácido tánico la fracción de sobrevida fue de 0.33 ± 0.03 y 0.30 ± 0.03 respectivamente. Se observó en las poblaciones irradiadas un aumento significativo de la probabilidad de mutagénesis. En el caso de los tratamientos combinados se observó que la frecuencia mutagénica fue significativamente menor (gamma Tannat: 33%, gamma ácido tánico: 45% ). Estos resultados preliminares podrían indicar radioprotección moderada por parte de los compuestos estudiados, efecto que podría explicarse por las interacciones redox del ácido tánico y polifenoles contenidos en el vino con los radicales libres formados por las radiaciones ionizantes, además de la activación de vías de reparación genómica.

The red wine variety Vitis vinifera L. cv Tannat in recent years has gained relevance due to its high concentration of polyphenols, this could mean a protective role on the genome, reducing the formation of oxidative lesions. The effects at the cellular level of ionizing radiation on targets such as DNA, components of signal transduction cascades, result in lethal, mutagenic and recombinogenic lesions and delays in the cell cycle. Exponential phase populations of Saccharomyces cerevisiae exposed to gamma radiation (200 Gy) in the presence or absence of Tannat wine (10% v / v) or tannic acid (60 µg / ml) were used as a eukaryotic model. The probabilities of survival and mutagenic frequency in different conditions were estimated. Cellular samples exposed to ionizing radiation presented a survival fraction of 0.21 ± 0.02, while in samples irradiated in the presence of Tannat wine or tannic acid, the survival fraction was 0.33 ± 0.03 and 0.30 ± 0.03 respectively. A significant increase in the probability of mutagenesis was observed in irradiated populations. In the case of the combined treatments, it was observed that the mutagenic frequency was significantly lower (Tannat gamma: 33%, Tannic acid gamma: 45%). These preliminary results could indicate moderate radioprotection by the compounds studied, an effect that could be explained by the redox interactions of tannic acid and polyphenols contained in wine with the free radicals formed by ionizing radiation, in addition to the activation of genomic repair pathways.

A variedade de vinho tinto Vitis vinifera L. cv Tannat nos últimos anos tem ganhado relevância devido à sua alta concentração de polifenóis, o que pode significar um papel protetor do genoma, reduzindo a formação de lesões oxidativas. Os efeitos no nível celular da radiação ionizante em alvos como o DNA, componentes de cascatas de transdução de sinal, resultam em lesões letais, mutagênicas e recombinogênicas e atrasos no ciclo celular. Populações de fase exponencial de Saccharomyces cerevisiae expostas à radiação gama (200 Gy) na presença ou ausência de vinho Tannat (10% v / v) ou ácido tânico (60 µg / ml) foram utilizadas como modelo eucariótico. Foram estimadas as probabilidades de sobrevivência e frequência mutagênica em diferentes condições. As amostras celulares expostas à radiação ionizante apresentaram uma fração de sobrevivência de 0,21 ± 0,02, enquanto nas amostras irradiadas na presença de vinho Tannat ou ácido tânico, a fração de sobrevivência foi de 0,33 ± 0,03 e 0,30 ± 0,03, respectivamente. Um aumento significativo na probabilidade de mutagênese foi observado nas populações irradiadas. No caso dos tratamentos combinados, observou-se que a frequência mutagênica foi significativamente menor (Tannat gama: 33%, ácido tânico gama: 45%). Esses resultados preliminares podem indicar radioproteção moderada pelos compostos estudados, efeito que pode ser explicado pelas interações redox do ácido tânico e polifenóis contidos no vinho com os radicais livres formados pela radiação ionizante, além da ativação de vias de reparo genômico.

Radioprotective natural products as alternative complements in oncological radiotherapy / Productos naturales radioprotectores como complementos alternativos en la radioterapia oncológica

Humans when exposed to harmful ionising radiations suffer from various pathophysiological disorders including cancer. Radiotherapy is a treatment where these cancerous cells within a tumor aretargeted and killed by means of high energy waves. This therapy is very expensive and involves highly sophisticated instruments. In addition to this, most synthetic radioprotectors including Amifostine have been found to possess toxicity. This led researchers to develop a novel, economically viable, and efficient therapeutic alternative to radiation therapy. The last two decades have observed a major shift towards investigating natural products as radioprotectors, as these are immensely effective in terms of their potential bioequivalence relative to many of the established synthetic compounds available. Taking into account the limitations of radiation therapy, an approach 'Integrative Oncology' that involves a combination of both traditional and conventional medical treatment are used nowadays to treat patients suffering from cancer and associated mental and psychological disorders.

Los seres humanos, cuando se exponen a radiaciones ionizantes nocivas, sufren diversos trastornos fisiopatológicos, incluido el cáncer. La radioterapia es un tratamiento en el que estas células cancerosas dentro de un tumor son atacadas y destruidas por medio de ondas de alta energía. Esta terapia es muy cara e implica instrumentos muy sofisticados. Además de esto, se ha descubierto que la mayoría de los radioprotectores sintéticos, incluida la amifostina, poseen toxicidad. Esto llevó a los investigadores a desarrollar una novedosa, económicamente viable y eficiente alternativa terapéutica a la radioterapia. En las dos últimas décadas se ha observado un cambio importante hacia la investigación de productos naturales como radioprotectores, ya que son inmensamente eficaces en términos de su potencial bioequivalencia en relación con muchos de los compuestos sintéticos establecidos disponibles. Teniendo en cuenta las limitaciones de la radioterapia, hoy en día se utiliza un enfoque de "Oncología Integrativa" que implica una combinación de tratamiento médico tradicional y convencional para tratar a pacientes que padecen cáncer y trastornos mentales y psicológicos asociados.

Toll-like Receptor Agonists in Radiation Protection / 中国医学科学院学报

Ionizing radiation causes the massive apoptosis of human tissue cells,leading to dysfunction of the gastrointestinal tract and hematopoietic system.Thus,high-efficiency,low-toxicity radiation protection drugs are urgently needed.Toll-like receptor agonists have been developed based on the anti-apoptotic mechanism of tumor cells in recent years,which exert their radioprotective effects by activating downstream pathways,mainly nuclear factor-κB.Here we elucidate several agonists of Toll-like receptors involved in radiation protection,with an attempt to inform the research and development of new radiation protection agents.

Hiposialia y Xerostomía Post Irradiación: Terapias Innovadoras en el Campo Biomolecular / Hyposialia and Xerostomy Post Irradiation: Innovative Therapies in the Biomolecular Field

Las glándulas salivales humanas pueden ser gravemente lesionadas por la radioterapia utilizada contra neoplasias de cabeza y cuello, produciendo hiposialia y xerostomía, las cuales afectan la salud oral y sistémica, mermando la calidad de vida de la persona. Los tratamientos convencionales actuales están diseñados para disminuir los síntomas, sin actuar sobre los cambios fisiopatológicos que se dan a nivel glandular. Esta revisión intenta analizar aquellas terapias preventivas y/o curativas que están desarrollándose en el campo biomolecular y que tienen un futuro prometedor por sus características innovadoras: terapia génica, terapia con células madre y terapia con factores de crecimiento. Se evidencia un aporte adicional de la nanotecnología, la cual está mejorando las vías de aplicación de los tratamientos.

Human salivary glands can be seriously injured by the radiotherapy used against head and neck neoplasms, producing hyposialia and xerostomy, which affect oral and systemic health, diminishing the person's quality of life. Current conventional treatments are designed to reduce symptoms, without acting on the pathophysiological changes that occur at the glandular level. This review attempts to analyze those preventive and /or curative therapies that are developing in the biomolecular field and that have a promising future due to their innovative features: Gene therapy, stem cell therapy and growth factor therapy. An additional contribution of nanotechnology is evident, which is improving the routes of treatment application.

Radioprotective effect of sodium selenite on mandible of irradiated rats

Abstract The purpose of this study was to test the radioprotective effect of selenium in the bone microarchitecture of irradiated rats mandibles. Forty rats were separated into 4 groups with 10 animals: control group (CG), irradiated group (IG), sodium selenite group (SSG) and sodium selenite irradiated group (SSIG). A single dose of 0.8 mg/kg sodium selenite was administered intraperitoneally in the SSG and SSIG groups. One hour later, animals of IG and SSIG groups were irradiated with 15 Gy of x-rays. Forty days after radiation a bilateral extraction of the mandibular first molars was performed. After the extraction procedure, five rats were killed after fifteen days and others five after thirty days. Micro- computed tomography was used to evaluate cortical and trabecular bone of each rat. The mean and standard deviation of each bone microarchitecture parameter were analyzed using the statistical test of two-way Analysis of Variance (ANOVA). At 15 days, the bone volume presented higher values in the CG and SSG groups (p=0.001). The same groups presented statistically significant higher values when bone volume fraction (p<0.001) and trabecular thickness (p<0.001) were analyzed. At 30 days, it was observed that in relation to the bone volume fraction, SSG group presented the highest value while SSIG group had the lowest value, with statistically significant difference (p=0.016). Sodium selenite demonstrated a median radioprotective effect in the bone microarchitecture of irradiated mandibles, which indicates the substance may be a potential radioprotective agent against chronic effects of high doses of ionizing radiation.

Resumo O propósito deste estudo foi testar o efeito radioprotetor do selênio na microarquitetura óssea de mandíbulas de ratos irradiados. Quarenta ratos foram separados em 4 grupos com 10 animais: grupo controle (GC), grupo irradiado (GI), grupo selenito de sódio (SSG) e grupo selenito de sódio irradiado (SSIG). Uma dose única de 0,8 mg/kg de selenito de sódio foi administrada intraperitonealmente nos grupos SSG e SSIG. Uma hora depois, os animais dos grupos IG e SSIG foram irradiados com 15 Gy de raios-x. Quarenta dias após a irradiação foi realizada extração bilateral dos primeiros molares inferiores. Após o procedimento de extração, cinco ratos foram mortos após quinze dias e outros cinco após trinta dias. A microtomografia computadorizada foi utilizada para avaliar o osso cortical e trabecular de cada rato. A média e o desvio padrão de cada parâmetro da microarquitetura óssea foi analisada pelo teste estatístico de Análise de Variância dois fatores (ANOVA), seguido por comparações post hoc com o teste de Tukey. Após 15 dias, o volume ósseo apresentou valores mais elevados nos grupos GC e GNS (p=0,001). Os mesmos grupos apresentaram valores estatisticamente significantes maiores quando se analisou fração de volume ósseo (p<0,001) e espessura trabecular (p<0,001). Após 30 dias, observou-se que, em relação à fração de volume ósseo, o grupo SSG apresentou o maior valor enquanto o grupo SSIG apresentou o menor valor, com diferença estatisticamente significante (p=0,016). O selenito de sódio demonstrou um efeito radioprotetor mediano na microarquitetura óssea das mandíbulas irradiadas, o que indica que a substância pode ser um potencial agente radioprotetor contra os efeitos crônicos da radioterapia.

MMP Inhibitor Ilomastat Improves Survival of Mice Exposed to γ-Irradiation / 生物医学与环境科学（英文）

There is still a need for better protection against or mitigation of the effects of ionizing radiation following conventional radiotherapy or accidental exposure. The objective of our current study was to investigate the possible roles of matrix metalloproteinase inhibitor, ilomastat, in the protection of mice from total body radiation (TBI), and the underlying protective mechanisms. Ilomastat treatment increased the survival of mice after TBI. Ilomastat pretreatment promoted recovery of hematological and immunological cells in mice after 6 Gy γ-ray TBI. Our findings suggest the potential of ilomastat to protect against or mitigate the effects of radiation.

The toxicological mechanisms and detoxification of depleted uranium exposure

Depleted uranium (DU) has been widely applied in industrial and military activities, and is often obtained from producing fuel for nuclear reactors. DU may be released into the environment, polluting air, soil, and water, and is considered to exert both radiological and chemical toxicity. In humans and animals, DU can induce multiple health effects, such as renal tubular necrosis and bone malignancies. This review summarizes the known information on DU's routes of entry, mechanisms of toxicity, and health effects. In addition, we survey the chelating agents used in ameliorating DU toxicity.

Potential radioprotective effect of AT1 receptor antagonists against morphological and ultrastructural changes in the testes induced by ionizing radiation / Potencial efecto radioprotector de antagonistas del receptor AT1 contra los daños morfológicos y ultraestructurales en los testículos inducido por la radiación ionizante

Radiotherapy is a source of human exposure to ionizing radiation. This pure energy causes deleterious effects on tissues, which result from oxidative stress, a phenomenon in which there is the participation of the Renin-Angiotensin System (RAS). The male genital organs are extremely radiosensitive and the action of radiation in the testes can significantly affect spermatogenesis. In search of potential radioprotective for male genital system, this study investigated whether the AT1 receptor antagonists minimize radiation-induced damage to reproductive tissues, by decreasing oxidative stress. Male Wistar rats were divided into six groups: 0 Gray (Gy) (control), 5 Gy (single dose in the scrotal area), telmisartan, losartan, 5Gy+telmisartan and 5Gy+losartan. The treatment started the day after irradiation with losartan 34 mg/kg (two times/day) and telmisartan 12 mg/kg (one time/day) during 60 days. For ultrastructural analysis, the testis fragments were fixed in 2 % glutaraldehyde and 4 % paraformaldehyde in 0.1 M phosphate buffer, pH 7.3. The material was postfixed for 2 h in 1 % osmium tetroxide. For collagen evaluation, the sections were stained with Picrosirius-red method. Serum testosterone was determined. The date showed the deleterious effects of gamma radiation on testicular ultrastructure. Rich accumulation of collagen fibers in the interstitium was observed in the irradiated groups, especially the irradiated and nontreated testes. No significant difference was detected in serum testosterone concentration among the studied experimental groups. Treatments with telmisartan and losartan influenced the onset of attenuation on ultrastructural damages arising from ionizing radiation. Although the data strongly suggest that AT1 receptor antagonists may promote radioprotection to the testes, further studies with a longer duration of treatment are required for these potentially positive effects to be maximized and, therefore, to better characterize radioprotection to reproductive parameters.

El tratamiento radioterápico es una fuente de exposición del ser humano a la radiación ionizante. Esta energía pura causa efectos deletéreos en los tejidos, debido al estrés oxidativo, fenómeno donde hay participación del Sistema Renina-Angiotensina. Los órganos genitales masculinos son extremadamente radiosensibles y la acción de la radiación en los testículos puede afectar significativamente la espermatogénesis. En la búsqueda de potenciales radioprotectores, este estudio ha investigado fármacos antagonistas del receptor AT1 que minimizan los daños radioinduzidos en los tejidos reproductivos, por medio de la disminución del estrés oxidativo. Ratones Wistar machos fueron distribuidos en seis grupos: grupo 0 Gray (Gy) (control), grupo 5 Gy (dosis única en el área escrotal), grupo telmisartán, grupo losartán, grupo 5Gy+telmisartán y grupo 5Gy+losartán. El tratamiento empezó en el día siguiente a la irradiación con losartán 34 mg/kg (2x/día) y telmisartán 12 mg/kg (1x/día), durante 60 días. Para el análisis ultraestructural, los testículos se fijaron en glutaraldehido (2 %) y paraformaldehido (4 %) con tampón de fosfato 0,1 M, pH 7,3. El material fue post-fijado en tetróxido de osmio (1 %). Para evaluar el colágeno fue utilizado el método Picrosirius Red. Fue determinada la concentración sérica de testosterona. Los datos mostraron los efectos deletéreos de los rayos gamma sobre la ultraestructura testicular. Fue observada una rica deposición de colágeno en el intersticio en los grupos irradiados, especialmente en el irradiado y no tratado. Entre los grupos, no se detectó ninguna diferencia significativa en la concentración sérica de testosterona. Los tratamientos con telmisartán y losartán influenciaron el comienzo de la atenuación de los cambios en la ultraestructura testicular de la radiación. A pesar de que los datos sugieren que los antagonistas del receptor AT1 pueden promover radioprotección a los testículos, estudios complementarios con una duración de tratamiento más extendida son necesarios para que los efectos potencialmente positivos sean maximizados y, por supuesto, puedan mejorar la caracterizacion de la radioprotección a los parámetros reproductivos.

Meloxicam as a Radiation-Protective Agent on Mandibles of Irradiated Rats

Abstract This study evaluated the action of ionizing radiation and the possible radioprotective effect of the non-steroidal anti-inflammatory drug meloxicam on the bone physiology of rat mandibles by assessing the alveolar socket healing and bone strength. Forty male Wistar rats were divided in 4 groups (n=10): control (CG), irradiated (IG), meloxicam (MG), meloxicam irradiated (MIG). A dose of 0.2 mg/kg meloxicam was administered to MG and MIG. After this, IG and MIG were irradiated with 15 Gy radiation dose in the mandible. Forty days after the above procedures, the mandibular first molars were extracted and the animals were killed after 15 or 30 days (n=5). Micro-computed tomography and bending test were used to evaluate alveolar socket healing and bone strength, respectively. At 15 days, bone volume, bone volume fraction and trabecular thickness were higher in the CG and MG than in the IG and MIG; and trabecular separation was higher in the IG compared with the others. At 30 days, there was a difference only in trabecular separation, which was higher in IG than in CG and MG, and MIG did not differ from the others. Bone strength was lower in IG compared with CG and MG, and MIG did not differ from the others. In conclusion, the ionizing radiation affected the bone physiology of rat mandibles, delaying the alveolar socket healing and reducing the bone strength. Moreover, the meloxicam had a positive effect on the trabecular separation in alveolar socket healing and on the bone strength.

Resumo Este estudo avaliou a ação da radiação ionizante e o possível efeito radioprotetor do anti-inflamatório não esteroide meloxicam na fisiologia óssea de mandíbulas de rato por meio da análise da reparação alveolar e da resistência óssea. Quarenta ratos Wistar machos foram divididos em 4 grupos (n=10): controle (GC), irradiado (GI), meloxicam (GM), meloxicam irradiado (GMI). Administrou-se uma dose única de 0,2 mg/kg de meloxicam no GM e GMI. Posteriormente, o GI e GMI foram irradiados com dose de 15 Gy na região de mandíbula. Decorridos 40 dias dos procedimentos acima, extraiu-se os primeiros molares inferiores dos animais, que foram mortos após 15 e 30 dias (n=5). Utilizou-se a microtomografia computadorizada e o teste de flexão para avaliação da reparação alveolar e da resistência óssea, respectivamente. Aos 15 dias, o volume ósseo, a fração de volume ósseo e a espessura trabecular foram maiores no GC e GM comparados ao GI e GMI; já a separação trabecular foi maior no GI em relação aos demais. Aos 30 dias, houve diferença apenas na separação trabecular, que foi maior no GI em comparação ao GC e GM, não tendo o GMI diferido dos demais. A resistência óssea no GI foi menor em relação ao GC e GM, não tendo o GMI diferido dos demais. Concluiu-se que a radiação ionizante afetou a fisiologia óssea das mandíbulas de rato, promovendo atraso na reparação alveolar e redução da resistência óssea; além disso, o meloxicam, apresentou efeito positivo na separação trabecular da reparação alveolar e na resistência óssea.

Short- and long-term effects of zinc treatment on lacrimal gland histopathology and tear functions tests in radioiodine-administered rats / Efeitos de curto e longo prazo do tratamento com zinco na histopatologia da glândula lacrimal e funções lacrimais em ratos que receberam iodo radioativo

ABSTRACT Purpose: To investigate the short-term (1 week) and long-term (8 weeks) protective effects of zinc administration on radioiodine (RAI)-induced lacrimal gland damage of rats. Methods: A total of 40 rats were divided into two groups: an RAI group (n=20), which was administrated a single dose of 3 mCi of 131I and 1 mL physiologic saline for 7 days by gastric gavage, and a zinc group (n=20), which received a single dose of 3 mCi of 131I and 1 mL of physiologic saline containing zinc sulfate at a concentration of 10 mg/kg concentration for 7 days by gastric gavage. All rats underwent tear function tests before and 1 week after RAI administration. About 1 week after irradiation, half of the animals in each group were sacrificed and the extraorbital lacrimal glands were removed for histopathological examination. The remaining animals of the groups underwent the same procedures at 8 weeks after irradiation. Results: In the RAI and zinc groups, the mean tear production was 3.75 ± 1.55 and 3.65 ± 1.53 mm at baseline, 2.10 ± 1.07 and 3.30 ± 1.34 mm at week 1 (p=0.004), and 3.22 ± 1.48 and 3.50 ± 1.78 mm at week 8, respectively; further, the mean corneal fluorescein staining scores were 4.65 ± 2.16 and 4.80 ± 2.21 points at baseline, 7.85 ± 1.90 and 5.45 ± 2.06 points at week 1 (p=0.001), and 5.44 ± 2.13 and 4.90 ± 2.08 at week 8, respectively. The histopathological changes in rat lacrimal glands at weeks 1 and 8 were consistent with the tear function test results. Conclusions: Zinc treatment seems to be protective against RAI-induced lacrimal gland damage of rats, particularly in the acute period.

RESUMO Objetivo: Investigar se o tratamento com zinco tem efeito protetor, no curto prazo (1 semana) e longo prazo (8 semanas), sobre os danos induzidos na glândula lacrimal por iodo radiotativo (RAI) em ratos. Métodos: Quarenta ratos foram divididos em dois grupos. No grupo RAI (n=20) foi administrada uma única dose de 3 mCi 131I e 1 cc de solução salina fisiológica durante 7 dias, por gavagem gástrica. O grupo zinco (n=20) recebeu uma dose única de 3 mCi 131I e 1 cc de solução salina fisiológica contendo sulfato de zinco na concentração de 10 mg/kg durante 7 dias por gavagem gástrica. Os testes de função lacrimal foram realizadas para todos os animais antes e após uma semana da administração da RAI. Em seguida, após 1 semana da administração, metade dos animais de cada grupo foi sacrificada e as glândulas lacrimais extraorbitais foram removidas para exame histopatológico. Os animais remanescentes dos grupos foram submetidos aos mesmos procedimentos após 8 semanas a radiação. Resultados: As médias de produção lacrimal foram de 3,75 ± 1,55 e 3,65 ± 1,53 mm na linha de base, 2,10 ± 1,07 e 3,30 ± 1,34 mm na 1a semana (p=0,004), e 3,22 ± 1,48 e 3,50 ± 1,78 mm na 8a semana, para os grupos RAI e zinco, respectivamente. As pontuações médias de coloração fluoresceína foram 4,65 ± 2,16 e 4,80 ± 2,21 no início do estudo, 7,85 ± 1,90 e 5,45 ± 2,06 na primeira semana (p=0,001), 5,44 ± 2,13 e 4,90 ± 2,08 pontos na 8a semana, para os grupos RAI e zinco, respectivamente. As alterações histopatológicas das glândulas lacrimais em 1 e 8 semanas foram consistentes com os testes de função lacrimal resultados. Conclusões: O tratamento de zinco parece ser protetor sobre os danos glândula lacrimal induzidos por RAI em ratos, especialmente no período agudo.

Efecto radioprotector del piruvato de etilo, solo o como coadyuvante de la amifostina / Radioprotective effect of ethyl pyruvate alone or as a coadyuvant of amifostine / Efeito radioprotetor do piruvato de etila, sozinho ou como um coadjuvante de amifostina

Entre los radioprotectores con uso clínico se destaca la amifostina (WR- 2721), eficaz pero con efectos secundarios que impiden su uso repetitivo. Es interés de los autores desarrollar radioprotectores menos tóxicos, por sí mismos o como coadyuvantes de amifostina. Ratas machos o hembras se expusieron a una dosis de rayos X de 2 Gy. Se ensayó el piruvato de etilo, solo o conjuntamente con amifostina. Cuarenta y ocho horas después de la exposición a la radiación, se realizó el recuento de eritrocitos, de leucocitos y la fórmula leucocitaria. Los efectos genotóxicos se evaluaron en leucocitos de sangre mediante el ensayo Cometa. Se realizaron también estudios de supervivencia a 60 días post-irradiación. En los animales irradiados disminuyeron los eritrocitos, y el recuento de leucocitos se redujo drásticamente respecto al control, presentando además una fórmula alterada. El tratamiento con piruvato de etilo resultó en una protección de los eritrocitos en ambos sexos. El daño genético disminuyó significativamente por el tratamiento con piruvato de etilo solo o combinado con amifostina, y en hembras se observó una mayor supervivencia solo con el tratamiento combinado. El piruvato de etilo mostró una acción radioprotectora significativa, que podría mejorarse aumentando la dosis o el tiempo de tratamiento, ya que tiene muy baja toxicidad.

Among the currently available radioprotectors, only amifostine (WR-2721) has shown in clinical trials to reduce radiation-induced toxicity. This compound is an efficient radioprotector but it exhibits some undesirable side effects which prevent its repetitive use. Efforts are directed to develop radioprotective agents with lower toxicity, with their own protective potential or suitable as coadyuvants of amifostine. The present study describes the results obtained by repetitive oral administration of ethyl pyruvate. Male or female rats were exposed to an X-ray dose of 2 Gy. Forty-eight hours after exposure to radiation, erythrocyte count, leukocyte and differential count were performed. Genotoxic effects were assessed in blood leukocytes by the Comet assay. Survival studies were also performed at 60 days post-irradiation. Eritrocyte and leukocyte were reduced in animals exposed to radiation compared to the control, also presenting an altered formula. Treatment with ethyl pyruvate resulted in a protection on erythrocytes of both sexes. Genetic damage was significantly decreased by ethyl pyruvate alone or combined with amifostine, and in females, higher survival was observed only with combined administration. Ethyl pyruvate showed a significant radioprotective action, which could be improved by increasing the dose or time of treatment because it has low toxicity.

Entre os radioprotetores com uso clínico destaca-se a amifostina (WR-2721) eficaz mas com efeitos secundários que impedem seu uso repetitivo. O interesse dos autores é desenvolver radioprotetores menos tóxicos, por si mesmos ou como coadjuvantes de amistofina. Ratos machos ou fêmeas foram expostos a doses de raios X de 2Gy. Ensaiou-se o piruvato de etila, só ou junto com amifostina. Quarenta e oito horas após a exposição à radiação foi realizada a contagem de eritrócitos, de leucócitos e da fórmula leucocitária. Efeitos genotóxicos foram avaliados em leucócitos do sangue pelo Ensaio Cometa. Estudos de sobrevivência foram também realizados a 60 dias pós-irradiação. Nos animais irradiados diminuíram os eritrócitos, e a contagem de leucócitos se reduziu drasticamente em comparação com o controle, apresentando também uma fórmula alterada. O tratamento com piruvato de etila resultou numa proteção dos eritrócitos em ambos os sexos. O dano genético diminuiu significativamente pelo tratamento com piruvato de etila sozinho ou combinado com amifostina, e nas fêmeas se observou maior sobrevivência só com o tratamento combinado. O piruvato de etila mostrou uma ação radioprotetora significativa, que poderia ser melhorada pelo aumento da dose ou do tempo de tratamento, visto que tem baixa toxicidade.

Nutritional supplementation with arginine protects radiation-induced effects. An experimental study

ABSTRACT PURPOSE: To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. METHODS: Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. RESULTS: After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). CONCLUSIONS: Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine.

L-carnitine has a protective effect on the colonic mucosa during abdominopelvic radiotherapy in rats

ABSTRACT PURPOSE: To evaluate histopathologically the radioprotective effect of L-carnitine on the colonic mucosa in rats undergoing abdominopelvic irradiation. METHODS: Thirty-two rats were randomly assigned to four experimental groups: intraperitoneal administration of normal saline (group 1) or L-carnitine (300 mL/kg; group 2), followed in groups 3 and 4, respectively, by one dose of abdominopelvic radiation (20 Gy) 30 min later. Rats were sacrificed 5 days after radiation, and their descending colons were resected for histopathological evaluation of the presence and severity of damage. RESULTS: Average damage scores did not differ significantly between groups 1 and 2 (0.13 ± 0.35 and 0.25 ± 0.46, respectively); the group 3 score was highest (10.25 ± 0.71), and the group 4 score (3.63 ± 1.41) was significantly lower than that of group 3 (both p = 0.0001). Pre-radiation L-carnitine administration significantly reduced mucosal thinning, crypt distortion, reactive atypia, inflammation, cryptitis, and reactive lymph-node hyperplasia (all p < 0.01). CONCLUSIONS: L-carnitine had a radioprotective effect on rat colonic mucosa. L-carnitine use should be explored for patients with gastrointestinal cancer, who have reduced serum L-carnitine levels.

Effects of L-Glutamine oral supplementation on prostate of irradiated rats

ABSTRACT Objectives To investigate the protective effect of L-Glutamine in animals undergone to ventral radiation when the target organ is not the prostate. Materials and Methods Wistar rats were divided into groups of 10 animals each: Controls (C), maintained under standard conditions and not exposed to radiation, Radiated group (R) undergone to abdominal radiation only and Radiated plus supplemented by L-glutamine group (R+G). The animals of group R+G were supplemented with L-glutamine at the beginning of the experiment until death in the 22nd day. The ventral prostate was dissected and processed for morphometrical analysis. The epithelial height, collagen density and acinar area were objectively assessed in histological sections. Results Epithelial height was significantly reduced in R group in comparison to C group (p= 0.005). However, there was no statistical difference between the C and R+G groups. Collagen surface density in the C and R groups were not statistically different, but a significant difference was observed when comparing groups R+G and R (p= 0.040). The R+G group values did not differ significantly from C group. The acinar prostate area of group R was similar to that of C (p= 0.971), but in R+G it was significantly reduced when compared with the C (p= 0.038) and R (p= 0.001) groups. Conclusions Pelvic radiation promotes structural modifications in ventral prostate of rats, which can be reduced by L-Glutamine.

The effect of amifostine on bacterial translocation after radiation induced acute enteritis

ABSTRACT PURPOSE: To investigate the effects of amifostine on bacterial translocation and overgrowth in colonic flora after acute radiation enteritis in a rat model. METHODS: Thirty-two female Wistar albino rats were divided into four groups: Group-1 (n=8): only normal saline was administered intraperitoneally. Group-2 (n=8): first serum saline was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. Group-3 (n=8): only amifostine 200 ml/kg was administered intraperitoneally and radiation was not applied. Group-4 (n=8): first amifostine 200 ml/kg was administered intraperitoneally and 30 minutes later 20 Gy radiation was applied to abdominopelvic region. On the 5th day after radiation, samples of mesenteric lymph tissues and cecal contents were taken by laparotomy for microbiological culture. RESULTS: Intraperitoneal amifostine administration significantly decreased the bacterial overgrowth related to radiation in colon but did not significantly decrease the bacterial translocation. CONCLUSİON: Although not providing a full protection on the damaged mucosal barrier, amifostine significantly decreased the bacterial overgrowth in the cecal content after high dose radiation. There is a need to find out appropriate amifostine dose under different radiation applications avoiding bacterial translocation in gastrointestinal system.

Effects of arbutin on radiation-induced micronuclei in mice bone marrow cells and its definite dose reduction factor

Background: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study,the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte [PCE/PCE+NCE] in order to show cell proliferation activity

Methods: Arbutin [50, 100, and 200 mg/kg] was intraperitoneally [ip] administered to NMRI mice two hours before gamma radiation at 2 and 4 gray [Gy]. The frequency of micronuclei in 1000 PCEs [MnPCEs] and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA,Tukey HSD test, and t-test

Results: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE [P<0.001] while reducing PCE/PCE+NCE [P<0.001] compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control [P<0.001]. All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor [DRF] showed DRF=1.93 for 2Gy and DRF-2.22 for 4 Gy

Conclusion: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation

Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

Abstract The purpose of this study was to perform a microcomputed tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a microcomputed tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey's post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05). The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues.