Topical agents for the prevention ofradiodermatitis in cancer patients: A systematic review / Agentes tópicos para prevenção de radiodermatiteem pacientes com câncer: revisão sistemática

Objetivo: Analisar as evidências sobre o efeito dos agentes tópicos empregados para a prevenção da radiodermatite em pacientes com câncer. Método: Revisão sistemática de estudos clínicos randomizados duplos-cegos construída conforme recomendações do Joanna Briggs Institute e busca nas bases de dados MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase, Scopus, além da literatura cinzenta. Utilizaram-se a ferramenta de avaliação crítica do JBI para ensaios clínicos randomizados para avaliar a possibilidade de viés, o Grading of Recommendations, Assessment, Development and Evaluation para a qualidade das evidências e o Gradepro® para recomendá-las. Resultados: Selecionaram-se 13 estudos que avaliaram diferentes agentes tópicos para prevenir a radiodermatite, a saber: corticosteroides, de ação antioxidante e fitoterápicos. A qualidade metodológica de cada estudo foi apropriada, mas a qualidade da evidência gerada pela reunião deles foi baixa, independentemente do tipo de agente tópico empregado, sugerindo que a confiança no seu efeito é limitada e tornando a força de recomendação fraca. Conclusão: Alguns agentes tópicos mostraram-se promissores para a prevenção de radiodermatite, mas as evidências aqui reunidas sobre a eficácia deles não permitem indicar seu uso para a prevenção de radiodermatite em pacientes com câncer. (AU)

Objective: To analyze the evidence on the effect of topical agents to prevent radiodermatitis in cancer patients. Methods: Systematic review of double-blind randomized clinical studies built according to JBI recommendations and search in the databases MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase and Scopus, in addition to the Gray Literature. The JBI critical assessment tool for randomized clinical trials was used to assess the possibility of bias, GRADE for the quality of evidence, and Gradepro® to recommend them. Results: Thirteen studies were selected that evaluated different topical agents to prevent radiodermatitis, namely: corticosteroids, with antioxidant action and herbal medicines. The methodological quality of each study was appropriate. Still, the quality of evidence generated by pooling them was low, regardless of the type of topical agent employed, suggesting that confidence in its effect is limited and weakening the strength of the recommendation. Conclusions: Some topical agents have shown promise for the prevention of radiodermatitis, but the evidence gathered here about their effectiveness does not indicate their use for the prevention of radiodermatitis in cancer patients. (AU)

Objetivo: Analizar la evidencia sobre el efecto de los agentes tópicos utilizados para la prevención de la radiodermatitis en pacientes con cáncer. Método: Revisión sistemática de estudios clínicos aleatorizados, doble ciego, elaborados según las recomendaciones del JBI y buscados en MEDLINE/PubMed, CINAHL, LILACS, Web of Science, Embase y Scopus, además de literatura gris. Se utilizó la herramienta de evaluación crítica JBI para ensayos clínicos aleatorios para evaluar la posibilidad de sesgo, GRADE para la calidad de la evidencia y Gradepro® para recomendarla. Resultados: Se seleccionaron trece estudios que evaluaron diferentes agentes tópicos para prevenir la radiodermatitis, a saber: corticosteroides, con acción antioxidante y fitoterapia. La calidad metodológica de cada estudio fue apropiada, pero la calidad de la evidencia generada al combinarlos fue baja, independientemente del tipo de agente tópico empleado, lo que sugiere que la confianza en su efecto es limitada y debilita la fuerza de la recomendación. Conclusión: Algunos agentes tópicos se han mostrado prometedores para la prevención de la radiodermatitis, pero la evidencia aquí reunida sobre su eficacia no nos permite indicar su uso para la prevención de la radiodermatitis en pacientes con cáncer. (AU)

Protective Effects of Antioxidants on Cyclophosphamide-Induced Ovarian Toxicity.

The most common limitation of anticancer chemotherapy is the injury to normal cells. Cyclophosphamide, which is one of the most widely used alkylating agents, can cause premature ovarian insufficiency and infertility since the ovarian follicles are extremely sensitive to their effects. Although little information is available about the pathogenic mechanism of cyclophosphamide-induced ovarian damage, its toxicity is attributed to oxidative stress, inflammation, and apoptosis. The use of compounds with antioxidant and cytoprotective properties to protect ovarian function from deleterious effects during chemotherapy would be a significant advantage. Thus, this article reviews the mechanism by which cyclophosphamide exerts its toxic effects on the different cellular components of the ovary, and describes 24 cytoprotective compounds used to ameliorate cyclophosphamide-induced ovarian injury and their possible mechanisms of action. Understanding these mechanisms is essential for the development of efficient and targeted pharmacological complementary therapies that could protect and prolong female fertility.

Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Efecto protector del aceite de Sacha inchi ( Plukenetía volubilis linneo ) en ratas Holtzman con inducción de artritis experimental / Protective effect of Sacha inchi oil ( Plukenetía volubilis linneo ) in Holtzman rats with induction of experimental arthritis

RESUMEN Objetivo. Demostrar cual es el resultado de la protección del aceite de Sacha inchi (SI) al realizar una inducción artificial de artritis al inyectar carragenina a ratas Holtzman. Métodos. Estudio cuantitativo, experimental y correlacional; se usaron 30 ratas macho: divididos en cinco grupos aleatorios : 1) Solución salina fisiológica (SSF) 2 mL/kg; 2) Carragenina (C) 0,1 mL solución 2% vía intraarticular, en la zona de la articulación del fémur con la tibia izquierda; 3) C y SI 250 mg/kg; 4) C y SI 1125 mg/kg; y 5) C y SI 2250 mg/ kg; determinándose tiempo (segundos), tipo de prensión (normal, pobre, regular, moderada, intensa), e inflamación pannus, fibrosis pannus, mediante estudio histopatológico. Se aplicó análisis de varianza, y los test de Tukey y Fisher. Resultados. Hubo mayor porcentaje de efecto antiinflamatorio dosis dependiente y tiempo de prensión a 2250 mg/Kg, seguido por 1125 mg/Kg. El estudio histopatológico mostró un pannus leve y fibrosis ausente con la dosis más alta; a dosis de 1125 mg/Kg de aceite SI hubo pannus moderado, y fibrosis leve. Conclusiones. Se demostró el resultado protector del aceite de Sacha Inchi (SI) aumentando y mejorando el tiempo tipo de prensión y reducción del pannus en la artritis inducida por carragenina en ratas Holtzman.

ABSTRACT Objective. To demonstrate the protective effect of Sacha inchi oil (SI) in arthritis induced by carrageenan in Holtzman rats. Methods. Quantitative, experimental and correlational study; 30 rats, males, randomly distributed in 5 groups were used: 1) SSF 2 mL/kg; 2) Carrageenan; 3) 4) and 5) Sacha inchi. Except for the control, they received 0.1 mL 2% carrageenan intra-articularly (the area of the femur joint with the left tibia); sacha inchi oil orally 225, 1125 and 2250 mg/kg correspondingly; determining time (seconds), type of grip (normal, poor, regular, moderate, intense), and pannus inflammation, pannus fibrosis by means of histopathological study. Applying analysis of variance, Tukey and Fisher test. Results. There was a higher percentage of dose-dependent anti-inflammatory effect and grasp time at 2250 mg/Kg, followed by 1125 mg/Kg; and the histopathological study showed mild pannus and absent fibrosis with the highest dose, in contrast to doses of 1125 mg/Kg of oil there was moderate pannus, and mild fibrosis. Conclusions. The protective effect of Sacha inchi oil (SI) has demonstrated by increasing the time and improving the type of grasp and reducing the pannus in arthritis induced by carrageenan in Holtzman rats.

Protective effect of polysaccharides isolated from the seeds of Cuscuta chinensis Lam. on 5-fluorouracil-induced intestinal mucositis in mice

Purpose: To evaluate the protective effect of Cuscuta chinensis Lam. polysaccharides (PCCL) on 5-fluorouracil-(5-FU)-induced intestinal mucositis (IM) in mice. Methods: PCCL was orally administered at a dose of 20 mg·kg­1 for 7 days and its protective effect on 5-FU-induced IM (5-FU, 50 mg·kg­1 for 5 days) was evaluated by monitoring changes in body weight, degree of diarrhea, levels of tissue inflammatory factors (tumor necrosis factor α, interleukin 6, and interleukin 1ß levels), apoptosis rates, and the expression levels of caspase-3, Bax and Bcl-2. Results: The severity of mucosal injury (as reflected by body weight changes, degree of diarrhea, height of villi, and damage to crypts) was significantly attenuated by PCCL administration. PCCL also reduced the levels of tissue inflammatory factors, the apoptosis rate, and the expression of caspase-3 and Bax, and increased Bcl-2 expression. Conclusions: PCCL administration may be significantly protective against 5-FU-induced IM by inhibiting apoptosis and regulating the abnormal inflammation associated with it.

Does the administration of meloxicam before head and neck radiotherapy reduce the risk of mandibular osteoradionecrosis? An animal model study.

OBJECTIVE: To assess whether the administration of meloxicam before head and neck radiotherapy reduces the risk of mandibular osteoradionecrosis in rats. MATERIAL AND METHODS: Sixty male Wistar rats were randomly divided into 6 groups (n = 10) according to the meloxicam administration and radiation therapy: control (C), irradiated (I), single dose of meloxicam (M1), single dose of meloxicam and irradiated (M1I), triple dose of meloxicam (M3), triple dose of meloxicam and irradiated (M3I). Meloxicam was administrated (20 mg/kg per dose) 1 h before the radiation therapy (single dose of 20 Gy) and 24 h and 48 h after the radiation therapy for groups with two additional doses. Ten days after the radiation therapy, the three right mandibular molars were extracted from all rats, who were euthanatized after 21 or 35 days (n = 5 per group). The mandibles were assessed by macroscopic evaluation and micro-CT analysis. RESULTS: The right hemimandibles of the irradiated groups revealed macroscopic signs of osteoradionecrosis, and those of the non-irradiated groups revealed complete gingival healing. A significant delay in alveolar socket healing in all irradiated groups was observed in the micro-CT assessment regardless meloxicam treatment. CONCLUSION: The administration of meloxicam before head and neck radiotherapy does not reduce the risk of mandibular osteoradionecrosis when associated to dental extractions. CLINICAL RELEVANCE: Since meloxicam has been shown to be a potential radiation-protective agent, and osteoradionecrosis physiopathology is believed to be related to an inflammatory process, possible interactions are relevant to be investigated.

The evaluation of shear bond strength of resin-modified glass ionomer cement with the addition of 45S5 bioactive glass using two conventional methods / La evaluación de la resistencia al cizallamiento del cemento de ionómero de vidrio modificado con resina con la adición de vidrio bioactivo 45S5 utilizando dos métodos convencionales

Introduction: There is a high prevalence of enamel caries around brackets due to the young age of the majority of orthodontic patients, and to the difficulty of plaque removal in presence of orthodontic appliances. Recently, protective agents such as bioactive glasses (BGs) were introduced to enhance remineralization and prevent demineralization of tooth structures. This study aimed to assess the shear bond strength (SBS) of resin-modified glass ionomer cement (RMGIC) with addition of 45S5 BG to enhance its remineralizing potential using two conventional methods. Material and methods: This in-vitro experimental study evaluated three groups (n=20) of orthodontic brackets bonded to enamel using Transbond XT (group 1), light-cure RMGIC (group 2) and RMGIC with BG added (group 3). Samples underwent 7000 thermal cycles and their SBS was measured. The adhesive remnant index (ARI) score was also determined. Quantitative data were analyzed using one-way ANOVA while qualitative data were analyzed using a chi-square test. Discussion: The results showed no significant difference in SBS between study groups, however the ARI scores were significantly different among the groups. The RMGIC group showed the highest ARI while RMGIC doped with BG showed the lowest ARI score. Conclusion: Addition of 30% w/v 45S5 BG to RMGIC does not cause a significant change in SBS of orthodontic brackets bonded to enamel, while resulting in less amount of luting agent remnants on the enamel surface after debonding.

Introducción: Existe una alta prevalencia de caries del esmalte alrededor de los brackets debido a la corta edad de la mayoría de los pacientes de ortodoncia y a la dificultad de remoción de la placa en presencia de aparatos de ortodoncia. Recientemente, se introdujeron agentes protectores como los vidrios bioactivos (VB) para mejorar la remineralización y prevenir la desmineralización de las estructuras dentales. Este estudio tuvo como objetivo evaluar la resistencia al cizallamiento (RC) del cemento de ionómero de vidrio modificado con resina (CIVMR) con la adición de 45S5 BG para mejorar su potencial remineralizante utilizando dos métodos convencionales. Material y Métodos: Este estudio experimentalin vitro evaluó tres grupos (n = 20) de brackets de ortodoncia adheridos al esmalte usando Transbond XT (grupo 1), CIVMR fotopolimerizable (grupo 2) y CIVMR con VB agregado (grupo 3). Las muestras se sometieron a 7000 ciclos térmicos y se midió su RC. También se determinó la puntuación del índice de restos de adhesivo (IRA). Los datos cuantitativos se analizaron mediante ANOVA de una vía, mientras que los datos cualitativos se analizaron mediante una prueba de chi-cuadrado. Discusión: Los resultados no mostraron diferencias significativas en la RC entre los grupos de estudio, sin embargo, los puntajes IRA fueron significativamente diferentes entre los grupos. El grupo CIVMR mostró el ARI más alto mientras que CIVMR dopado con VB mostró el puntaje IRA más bajo. Conclusión: La adición de un 30% p/v de 45S5 VB a CIVMR no causa un cambio significativo en la RC de los brackets de ortodoncia adheridos al esmalte, mientras que resulta en una menor cantidad de remanentes de agente de fijación en la superficie del esmalte después del desprendimiento. Resistencia al Corte.

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.

Factores moduladores de resiliencia en pacientes diagnosticadas con cáncer de mama / Modulating Factors of Resilience in Patients Diagnosed with Breast Cancer

Introducción: los factores que modulan la resiliencia actúan como agentes protectores de la salud y pueden influir en el afrontamiento de la enfermedad de los pacientes con cáncer. Objetivo: precisar las particularidades de los factores moduladores de la resiliencia según: optimismo, inteligencia emocional y apoyo social en pacientes diagnosticadas con cáncer de mama. Método: estudio descriptivo, prospectivo, de serie de casos, en el municipio Rodas entre 2014-2015. Incluyó a todas las pacientes diagnosticadas con cáncer de mama, con uno, tres y cinco años de supervivencia. Los instrumentos aplicados fueron: cuestionario de datos generales, examen de inteligencia emocional, cuestionarios de optimismo y de apoyo social. Las variables analizadas fueron: edad, nivel de escolaridad, estado civil, ocupación, presencia de optimismo, grado de inteligencia emocional, necesidad de apoyo. Se realizó un estudio en profundidad y se aplicaron los cuestionarios de datos generales, de optimismo, de apoyo social y examen de inteligencia emocional. Se utilizaron medidas de tendencia central, medidas de dispersión y el porciento como medida de resumen para variables cualitativas. Resultados: se estudiaron 37 mujeres, principalmente casadas, amas de casa, de nivel medio superior y con edad promedio 59,5 años. De los moduladores de la resiliencia, el optimismo estuvo presente en las pacientes con 3 y 5 años de evolución, predominó el grado medio de inteligencia emocional en la mayoría de las pacientes y perciben que necesitan entre casi nada y algo, de apoyo social. Conclusiones: existió homogeneidad en los aspectos sociodemográficos y clínicos de las pacientes. El optimismo estuvo menos presente en los inicios de la enfermedad, pero posteriormente se relacionó con la evolución en años. Las necesidades de apoyo social y emocional aumentaron con el tiempo de evolución de este padecimiento.

Introduction: resilience modulating factors serve as health protecting agents and can influence in facing the disease of patients with cancer. Objective: to specify the distinctive features of modulating resilience factors according to: optimism, emotional intelligence and social support in patients diagnosed with breast cancer. Methods: descriptive, prospective study, of a case series, in the municipality of Rodas from 2014 to 2015. It included all patients diagnosed with breast cancer, with one, three and five years of survival. The applied instruments were: general data questionnaire, emotional intelligence test, optimism and social support questionnaires. The variables analyzed were: age, level of schooling, marital status, occupation, presence of optimism, degree of emotional intelligence, support need. An in-depth study was carried out and the questionnaires of general data, optimism, social support and emotional intelligence examination were applied. Measures of central tendency, dispersion measures and percentage were used as a summary measure for qualitative variables. Results: 37 mainly married, housewives, were studied, senior high schooling and aged 59.5 years average. From the resilience modulators, optimism was present in patients with 3 and 5 years of evolution, an average degree of emotional intelligence predominated in most patients and they perceive that they need between almost nothing and something of social support. Conclusion: there was homogeneity in the socio-demographic and clinical aspects of the patients. Optimism was less present at the beginning of the disease, but later it was related to the evolution in years. Needs of social and emotional support increased with the time of evolution of this condition.

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.

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.

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

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.(AU)

Phytochemical analysis of hydroethanolic extract of Turnera diffusa Willd and evaluation of its effects on astrocyte cell death / Análise fitoquímica do extrato hidroetanólico de Turnera diffusa Willd e avaliação de seus efeitos na morte de astrócitos

ABSTRACT Objective To evaluate the phytochemical composition of hydroethanolic extracts from powdered aerial parts of Turnera diffusa Willd (Turneraceae; T. diffusa), as well as its toxicity in astrocytes. Methods Chemical analyses of hydroethanolic extract from powdered aerial parts ofT. diffusa were carried out using HPLC-DAD-ESI-MS/MS.In vitro assays using astrocytes culture were performed to evaluate cell death. Results Flavone-C, O-diglycosides, such as, luteolin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside, apigenin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside and apigenin-7-O-6”-p-coumaroylglucoside were the main compounds found in this hydroethanolic extract. Concentration time-effect demonstrated the toxicity of this extract at a concentration of 1,000µg/mL in astrocyte culture, after 6 and 24 hours of incubation. Conclusion In phytochemical analyses, important antioxidants (mainly flavonoids) were observed. T. diffusa extracts presented cytotoxic effect in high concentrations, leading to increased cell death in astrocyte culture.

RESUMO Objetivo Avaliar a composição fitoquímica do extrato hidroetanólico das partes aéreas de Turnera diffusa Willd (Turneraceae; T. diffusa) e sua toxicidade em astrócitos. Métodos Análises químicas do extrato hidroetanólico de partes aéreas de T. diffusa foram feitas por HPLC-DAD-ESI-MS/MS. Os ensaiosin vitro utilizaram culturas de astrócitos para avaliar morte celular. Resultados Flavonas-C, O-diglicosídeos, como, luteolina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo, apigenina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo e apigenina-7-O-6”-p-cumaroilglucosídeo foram os principais constituintes encontrados neste extrato hidroetanólico. Uma curva tempo-concentração demonstrou toxicidade desse extrato na concentração de 1.000µg/mL, na cultura de astrócitos após 6 e 24 horas de incubação. Conclusão Nas análises fitoquímicas, importantes antioxidantes, sobretudo flavonoides, foram observados. Extratos de T. diffusa apresentaram efeitos citotóxicos em altas concentrações, ocasionando aumento de morte celular em cultura de astrócitos.

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.

Evaluación de los arándanos como radioprotectores potenciales / Evaluation of blueberries as potential radioprotectors

Antecedentes: numerosos estudios han analizado la capacidad antioxidante de los arándanos. Considerando la citotoxicidad de las radiaciones ionizantes, mediada por radicales libres, es imperativo el análisis de fitocompuestos con efecto mitigante potencial. Objetivo: evaluar las propiedades radio-protectoras de de los arándanos, en relación con el daño genético inducido por rayos X. Materiales y métodos: el diseño experimental tuvo dos etapas: primero se ejecutó ensayo in vitro con diez muestras de sangre periférica de mujeres jóvenes no fumadoras. Cada muestra fue analizada mediante Ensayo Cometa en el siguiente grupo de tratamientos: control negativo, tratamiento con arándanos (0,232 mG/mL), irradiación con 4 Gy y tratamiento simultáneo arándanos/irradiación. Se contabilizaron 800 células/individuo, 200 por tratamiento, considerando su repetición. Posteriormente, se realizó ensayo in vivo con sangre periférica de dos mujeres, de condiciones similares a las anteriores, sometidas al consumo de extracto seco de arándanos durante 15 días consecutivos. El muestreo se realizó antes y después del tratamiento y se implementó el Cometa analizando 800 células/individuo, correspondientes al control negativo e irradiación con 4 Gy. Resultados: en ambas etapas, el tratamiento con arándanos demostró una reducción significativa (p<0,01) del daño genómico referido a las muestras irradiadas. Conclusiones: la suplementación dietaria con arándanos podría disminuir los efectos secundarios de la radioterapia, optimizando la calidad de vida del paciente oncológico.

Introduction: Numerous studies have analyzed the antioxidant capacity of blueberries. Considering the ionizing radiation cytotoxicity mediated by free radicals is imperative phytocompounds analysis with potential mitigating effect. Objective: To evaluate radio-protective properties of this fruit in relation to genetic damage induced by x-rays. Materials and methods: Experimental design had two stages. First an in vitro assay using 10 samples of peripheral blood of young and nonsmokers female. Each sample was analyzed by comet assay in the next set of treatments: negative control, treatment with blueberries (0,232 mG / mL), irradiation 4Gy and simultaneous blueberry/ irradiation treatment. Were counted 800 cells/individual, 200 per treatment, considering its repetition. Subsequently, an in vivo assay with peripheral blood of two women, of similar conditions and subject to the consumption of dried extract of blueberries for 15 consecutive days was performed. Sampling was performed before and after treatment and Comet was implemented by analyzing 800 cells / individual, corresponding to the negative control and irradiation with 4 Gy. Results: In both stages, treatment with blueberries showed a significant reduction (p <0.01) of genomic damage relative to irradiated samples. Conclusions: Dietary supplementation with blueberries may decrease the side effects of radiation therapy, optimizing the quality of life of cancer patients.

Effect of protective solutions and hydroxyethyl starch in the attenuation of the injuries of ischemia and reperfusion of splanchnic organs

PURPOSE: Vogt´s antioxidant solution (red blood cells, Ringer's solution, sodium bicarbonate, mannitol, allopurinol and 50% glucose) or its modification including hydroxyethyl starch (HES) were tested for the prevention of splanchnic artery occlusion shock. METHODS: Seventy rats were distributed in treatment (3), control (1), and sham (3) groups. Ischemia and reperfusion were induced by celiac, superior mesenteric and inferior mesenteric arteries occlusion for 40 min, followed by 60 min reperfusion or sham procedures. Controls received saline, both treatment and sham groups received the Vogt's solution, modified Vogt's solution (replacing Ringer's solution by HES), or HES. Mean arterial blood pressure (MABP), ileal malondialdehyde (MDA) and plasmatic MDA were determined, and a histologic grading system was used. RESULTS: At reperfusion, MABP dropped in all I/R groups. Only HES treatment was able to restore final MABP to the levels of sham groups. Plasmatic MDA did not show differences between groups. Ileum MDA was significantly higher in the control and treatment groups as compared to the sham group. Histology ranking was higher in the only in control group. CONCLUSIONS: Hydroxyethyl starch was able to prevent hemodynamic shock but not intestinal lesions. Both treatments with Vogt's solutions did not show any improvement. .

Effect of protective solutions and hydroxyethyl starch in the attenuation of the injuries of ischemia and reperfusion of splanchnic organs

PURPOSE: Vogt´s antioxidant solution (red blood cells, Ringer's solution, sodium bicarbonate, mannitol, allopurinol and 50% glucose) or its modification including hydroxyethyl starch (HES) were tested for the prevention of splanchnic artery occlusion shock.METHODS:Seventy rats were distributed in treatment (3), control (1), and sham (3) groups. Ischemia and reperfusion were induced by celiac, superior mesenteric and inferior mesenteric arteries occlusion for 40 min, followed by 60 min reperfusion or sham procedures. Controls received saline, both treatment and sham groups received the Vogt's solution, modified Vogt's solution (replacing Ringer's solution by HES), or HES. Mean arterial blood pressure (MABP), ileal malondialdehyde (MDA) and plasmatic MDA were determined, and a histologic grading system was used.RESULTS:At reperfusion, MABP dropped in all I/R groups. Only HES treatment was able to restore final MABP to the levels of sham groups. Plasmatic MDA did not show differences between groups. Ileum MDA was significantly higher in the control and treatment groups as compared to the sham group. Histology ranking was higher in the only in control group.CONCLUSIONS:Hydroxyethyl starch was able to prevent hemodynamic shock but not intestinal lesions. Both treatments with Vogt's solutions did not show any improvement.(AU)

Resveratrol plays important role in protective mechanisms in renal disease - mini-review / Resveratrol desempenha importante papel no mecanismo de proteção na doença renal - mini-revisão

Resveratrol (RESV) is a polyphenolic compound found in various plants, including grapes, berries and peanuts, and its processed foods as red wine. RESV possesses a variety of bioactivities, including antioxidant, anti-inflammatory, cardioprotective, antidiabetic, anticancer, chemopreventive, neuroprotective, renal lipotoxicity preventative, and renal protective effects. Numerous studies have demonstrated that polyphenols promote cardiovascular health. Furthermore, RESV can ameliorate several types of renal injury in animal models, including diabetic nephropathy, hyperuricemic, drug-induced injury, aldosterone-induced injury, ischemia-reperfusion injury, sepsis-related injury, and endothelial dysfunction. In addition, RESV can prevent the increase in vasoconstrictors, such as angiotensin II (AII) and endothelin-1 (ET-1), as well as intracellular calcium, in mesangial cells. Together, these findings suggest a potential role for RESV as a supplemental therapy for the prevention of renal injury.

Resveratrol (RESV) é um composto fenólico encontrado em várias plantas, como a uva e amendoim, e seus produtos derivados, como o vinho tinto. RESV possui uma variedade de bioatividades, incluindo antioxidantes, anti-inflamatória, cardioprotetoras, antidiabetes, anticancerígeno, quimiopreventivo, neuroprotetor, lipotoxicidade renal, e efeitos protetores renais. Numerosos estudos demonstraram que os polifenois promovem a saúde cardiovascular e podem reparar vários tipos de lesões renais em modelos animais, incluindo a nefropatia diabética, hiperuricemia, lesão induzida por droga, lesão induzida pela aldosterona, lesão de isquemia-reperfusão, lesões relacionadas com sepsis, e disfunção endotelial. Além disso, RESV pode prevenir o aumento de vasoconstritores, tais como angiotensina II (AII) e endotelina-1 (ET-1), bem como o cálcio intracelular, em células mesangiais. Em conjunto, estes resultados sugerem um importante papel para o RESV como uma terapia complementar na prevenção de lesões renais.

Capacidad atrapadora de radicales oxígeno (ORAC) y fenoles totales de frutas y hortalizas de Colombia / Oxygen radical absorbance capacity (ORAC) and phenolic content of fruits and vegetables from Colombia

Antecedentes: las frutas y hortalizas poseen un alto potencial nutricional y terapéutico, debido a la presencia de diferentes fitoquímicos, como los compuestos fenólicos que han sido relacionados con la actividad antioxidante. Con el fin de determinar la capacidad antioxidante en matrices alimentarias, uno de los métodos más utilizados es la capacidad atrapadora de radicales de oxígeno (ORAC). Objetivo: estimar el contenido de fenoles totales y la capacidad atrapadora de radicales de oxígeno (ORAC) en frutas y hortalizas colombianas. Materiales y métodos: el material vegetal fue liofilizado, seguido de un proceso de extracción para separar la fracción hidrofílica y lipófilica. El contenido de fenoles totales se determinó en la fracción hidrofílica por el método de Folin- Ciocalteu. La actividad antioxidante fue evaluada en la fracción hidrofílica y lipofílica por ORAC. Resultados: el contenido de fenoles totales varió entre 30,5 a 10.584,7 mg/100 g en las frutas y 12,4 a 1.377,2 mg/100 g en las hortalizas. Los valores ORAC obtenidos variaron desde 685,7 a 207.850,4 μmol trolox/100 g en las frutas y 372,3 a 32.047,9 μmol trolox/100 g en las hortalizas. La curuba y espinaca presentaron mejores propiedades antioxidantes de las frutas y hortalizas analizadas, respectivamente; con diferencias estadísticamente significativas frente a los demás alimentos de su grupo (p<0,05). Conclusión: los productos hortofrutícolas colombianos presentan posibles propiedades nutracéuticas por el aporte de compuestos fenólicos con actividad antioxidante.

Background: Fruits and vegetables have a high nutritional and therapeutic potential. It could be explained by presence of different phytochemicals, such as phenolic compounds, which have been associated with antioxidant activity. In order to determine antioxidant capacity in food matrices, one of the most widely used methods is oxygen radical absorbance capacity (ORAC). Objective: To estimate total phenolic content and ORAC in Colombian fruits and vegetables. Method and materials: Plant material was lyophilized, followed by an extraction process to separate hydrophilic and lipophilic fraction. Total phenolic content was estimated from hydrophilic fraction by Folin-Ciocalteu method. Antioxidant activity was evaluated in hydrophilic and lipophilic fractions by ORAC. Results: Total phenolic content varied from 30,5 to 10.584,7 mg/100 g in fruits, and 12,4 to 1.377,2 mg/100 g in vegetables. ORAC values were from 685,7 to 207.850,4 μmol trolox/100 g in fruits, and 372,3 to 32.047,9 μmol trolox/100 g in vegetables. Passion fruit and spinach had better antioxidant properties. Conclusions: Nutraceutical properties of Colombian fruits and vegetables may be explained by phenolic compounds content and antioxidant activity.