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.

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.

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.

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.

Radiosensitizers, radioprotectors, and radiation mitigators.

Radiotherapy is regarded as one of the most important therapeutic modality for the treatment of malignant lesions. This field is undergoing rapid advancements in the recent times. With the use of radiosensitizers and radioprotective agents, the course of radiotherapy has improved the sensitization of tumor cells and protection of normal cells, respectively. The aim of this paper was to critically review and analyze the available compounds used as radiosensitizers, radioprotectors, and radiation mitigators. For reviewing, the author used the electronic search for the keywords 'Radiosensitizers', 'Radioprotectors', 'Radiation mitigators' on PubMed for inclusion of previously published articles and further search of reference papers on individual radiosensitizing and radioprotecting agents was done. Radiosensitizers are agents that sensitize the tumor cells to radiation. These compounds apparently promote fixation of the free radicals produced by radiation damage at the molecular level. The mechanism of action is similar to the oxygen effect, in which biochemical reactions in the damaged molecules prevent repair of the cellular radiation damage. Free radicals such as OH + are captured by the electron affinity of the radiosensitizers, rendering the molecules incapable of repair. Radioprotectors are compounds that are designed to reduce the damage in normal tissues caused by radiation. These compounds are often antioxidants and must be present before or at the time of radiation for effectiveness. Other agents, termed mitigators, may be used to minimize toxicity even after radiation has been delivered. This article tries to discuss the various aspects of radiosensitizers, radioprotectors, and radiation mitigators including the newer agents.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

Radioprotective Effect of Vitamin E in Parotid Glands: a Morphometric Analysis in Rats

The aim of this study was to evaluate the radioprotective effect of vitamin E on rat parotid glands by morphometric analysis. Sixty male rats were divided into 5 groups (n=6): control, in which animals received olive oil solution; olive oil/irradiated, in which animals received olive oil and were irradiated with a dose of 15 Gy of gamma radiation; irradiated, in which animals were irradiated with a dose of 15 Gy gamma radiation; vitamin E, which received α-tocopherol acetate solution; vitamin E/irradiated, which received α-tocopherol acetate solution before irradiation with a dose of 15 Gy gamma rays. Half of the animals were euthanized at 8 h, and the remaining at 30 days after irradiation. Both parotid glands were surgically removed and morphometric analysis of acinar cells was performed. Data were subjected to two-way ANOVA and Tukey's test (α=0.05). Morphometric analysis showed a significant reduction in the number of parotid acinar cells at 30 days in olive oil/irradiated and irradiated groups. In groups evaluated over time a significant reduction was shown at 30 days in olive oil/irradiated and irradiated groups, indicating that ionizing radiation caused tissue damage. The vitamin E/irradiated group presented more acinar cells than the irradiated group, but no statistically significant difference was observed (p>0.05). In conclusion, vitamin E seems to have failed as a radioprotective agent on acinar cells in rat parotid glands.

O objetivo neste estudo foi avaliar o efeito radioprotetor da vitamina E sobre glândulas parótidas de ratos por meio de análise morfométrica. Sessenta ratos machos foram divididos em cinco grupos: controle, no qual os animais receberam solução de óleo de oliva; óleo de oliva irradiado, em que os animais receberam óleo de oliva e foram irradiados com uma dose de 15 Gy de radiação gama; irradiado, em que os animais foram irradiados com uma dose de 15 Gy de radiação gama; vitamina E, no qual receberam solução de acetato α-tocoferol; vitamina E irradiado, os quais receberam solução de acetato de α-tocoferol antes da irradiação com uma dose de 15 Gy de radiação gama. Metade dos animais foi eutanasiada em 8 h, e o restante aos 30 dias após a irradiação. Ambas as glândulas parótidas foram removidas cirurgicamente e análise morfométrica das células acinares foi realizada. Os dados foram submetidos à Análise de Variância com 2 fatores e teste de Tukey (α=0,05). A análise morfométrica mostrou uma redução significativa no número de células acinares da glândula parótida aos 30 dias nos grupos óleo irradiado e irradiado. Nos grupos avaliados ao longo do tempo uma redução significativa foi mostrada aos 30 dias nos grupos óleo irradiado e irradiado, indicando que a radiação ionizante causou danos teciduais. O grupo vitamina E/irradiado apresentou mais células acinares que o grupo irradiado, mas diferença estatisticamente significante não foi observada. Em conclusão, a vitamina E parece ter fracassado como um agente radioprotetor nas células acinares das glândulas parótidas de ratos.

Fotoproteção na prática clínica / Photoprotection in clinical practice

A exposição solar sem a adequada proteção pode ter efeitos agudos e crônicos prejudiciais à pele. A escolha do tipo de proteção solar depende da idade, fototipo de pele e das atividade individuais. Os autores fazem uma revisão bibliográfica sobre os tipos de radiação e a respectiva proteção solar.

The sun exposure with no adequate protection may have acute and chronic detrimental effects in skin. The choice of the type of photoprotection depends on the age, skin phototype and individual activities. The authors make a literature review about the types of radiation and photoprotection.

Síndrome de Gorlin

Contexto: A síndrome de Gorlin ou síndrome do nevo basocelular é desordem autossômica dominante causada por mutação no gene Patched, que faz parte da via de sinalização Hedgehog.Descrição do caso: O paciente descrito tem 67 anos, apresenta múltiplos carcinomas basocelulares com início desde os 17 anos, além de cistos odontogênicos, escoliose dorsal, pits palmoplantares, hipertelorismo e macrocefalia.Discussão: A síndrome é manifestada pela tríade de múltiplos carcinomas basocelulares, tumores odontogênicos ceratocísticos e anomalias esqueléticas. Outras alterações orgânicas podem estar presentes, sendo o meduloblastoma, tumor maligno da fossa posterior, causa potencial de morte.Conclusão: O diagnóstico precoce é importante para que terapias menos agressivas sejam realizadas. O tratamento envolve equipe multidisciplinar e o aconselhamento genético é mandatório.

Radioprotective effect of sodium selenite on bone repair in the tibia of ovariectomized rats

This studyevaluated protection by selenium (Se) in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Wistar rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of x-rays on the lower limb region. The animals were euthanized at 7, 14, 21 and 28 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/Se and Ov/Se/Irr groups. In conclusion, sodium selenite exerted a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity.

Esse estudo avaliou a proteção do selênio no processo de reparação óssea em ratas ovariectomizadas após irradiação. Para isso, 80 ratas Wistar foram divididas aleatoriamente em 4 grupos experimentais: ovariectomizado, ovariectomizado/selênio, ovariectomizado/irradiado e ovariectomizado/selênio/irradiado. Foi realizado um defeito ósseo na tíbia de todos os animais 40 dias após ovariectomia. Dois dias após essa cirurgia, os animais dos grupos ovariectomizado/selênio e ovariectomizado/selênio/irradiado receberam 0,8 mg Se/kg. Três dias após a cirurgia, os animais dos grupos ovariectomizado/irradiado e ovariectomizado/selênio/irradiado receberam 10 Gy de radiação X na região de membros inferiores. Os animais foram sacrificados 7, 14, 21 e 28 dias após a cirurgia para avaliação do processo de reparo ósseo, que foi realizado pela análise do número de trabéculas ósseas (coloração Tricrômico de Masson) e pela análise de birrefringência (coloração de Picrosirius). Foi observado atraso no processo de reparo ósseo no grupo ovariectomizado/irradiado e semelhança entre os grupos ovariectomizado, ovariectomizado/selênio e ovariectomizado/selênio/irradiado. Foi possível concluir que o selenito de sódio exerceu efeito radioprotetor no processo de reparação de tíbias em ratas ovariectomizadas sem toxicidade.

Effect of melatonin and time of administration on irradiation-induced damage to rat testes

The effect of ionizing irradiation on testes and the protective effects of melatonin were investigated by immunohistochemical and electron microscopic methods. Eighty-two adult male Wistar rats were divided into 10 groups. The rats in the irradiated groups were exposed to a sublethal irradiation dose of 8 Gy, either to the total body or abdominopelvic region using a 60Co source at a focus of 80 cm away from the skin in the morning or evening together with vehicle (20% ethanol) or melatonin administered 24 h before (10 mg/kg), immediately before (20 mg/kg) and 24 h after irradiation (10 mg/kg), all ip. Caspace-3 immunoreactivity was increased in the irradiated group compared to control (P < 0.05). Melatonin-treated groups showed less apoptosis as indicated by a considerable decrease in caspace-3 immunoreactivity (P < 0.05). Electron microscopic examination showed that all spermatogenic cells, especially primary spermatocytes, displayed prominent degeneration in the groups submitted to total body and abdominopelvic irradiation. However, melatonin administration considerably inhibited these degenerative changes, especially in rats who received abdominopelvic irradiation. Total body and abdominopelvic irradiation induced identical apoptosis and testicular damage. Chronobiological assessment revealed that biologic rhythm does not alter the inductive effect of irradiation. These data indicate that melatonin protects against total body and abdominopelvic irradiation. Melatonin was more effective in the evening abdominopelvic irradiation and melatonin-treated group than in the total body irradiation and melatonin-treated group.

Melatonin prevents inflammation and oxidative stress caused by abdominopelvic and total body irradiation of rat small intestine

We investigated the day-night differences in intestinal oxidative-injury and the inflammatory response following total body (TB) or abdominopelvic (AP) irradiation, and the influence of melatonin administration on tissue injury induced by radiation. Rats (male Wistar, weighing 220-280 g) in the irradiated groups were exposed to a dose of 8 Gy to the TB or AP region in the morning (resting period - 1 h after light onset) or evening (activity span - 13 h after light onset). Vehicle or melatonin was administered immediately before, immediately after and 24 h after irradiation (10, 2.0 and 10 mg/kg, ip, respectively) to the irradiated rats. AP (P < 0.05) and TB (P < 0.05) irradiation applied in the morning caused a significant increase in thiobarbituric acid reactive substance (TBARS) levels. Melatonin treatment in the morning (P < 0.05) or evening (P < 0.05) decreased TBARS levels after TB irradiation. After AP irradiation, melatonin treatment only in the morning caused a significant decrease in TBARS levels (P < 0.05). Although we have confirmed the development of inflammation after radiotherapy by histological findings, neither AP nor TB irradiation caused any marked changes in myeloperoxidase activity in the morning or evening. Our results indicate that oxidative damage is more prominent in rats receiving TB and AP irradiation in the morning and melatonin appears to have beneficial effects on oxidative damage irrespective of the time of administration. Increased neutrophil accumulation indicates that melatonin administration exerts a protective effect on AP irradiation-induced tissue oxidative injury, especially in the morning.

Efeito do propiltiouracil sobre a eficácia da dose terapêutica de iodo radioativo (I-131) no hipertiroidismo por doença de graves / The effect of propylthiouracil on the efficacy of radioiodine (I-131) therapy in gravesÆ hyperthyroidism / The effect of propylthiouracil on the efficacy of radioiodine (I-131) therapy in gravesÆ hyperthyroidism

Com objetivo de avaliar a influência das drogas antitiroidianas (AT) sobre a eficácia da dose terapêutica de iodo radioativo (DT), avaliamos retrospectivamente 226 prontuários de pacientes portadores de doença de Graves submetidos à DT no período entre 1990 e 2001: 58 pacientes sem antitiroidiano (AT), 119 em uso de propiltiouracil (PTU) e 49 em uso de metimazol (MMI). O estado funcional tiroidiano 9-12 meses pós-DT dividia os pacientes entre curados e não curados. Níveis elevados de T4 livre, captação de 131I em 24 h tiveram influência negativa sobre a taxa de cura, assim como menor dose de iodo administrada e maior volume do bócio (p< 0,05). O percentual de pacientes curados em uso de PTU previamente à DT foi de 70,2 por cento (84/119), enquanto nos pacientes em uso de MMI foi de 85,7 por cento (42/49), e de 84,5 por cento (49/58) nos pacientes sem AT pré-DT (p= 0,034). Em modelo de regressão multivariado, T4 livre > 4 ng/dl, maior volume do bócio, dose terapêutica < 10 mCi e o uso prévio de PTU tiveram relação com menores taxas de cura. Quando comparado ao grupo sem AT, concluímos que PTU implica em maior risco de falência pós-DT (OR= 3,13), o mesmo não ocorrendo com MMI (OR= 1,28).

Aiming at evaluating the effect of antithyroid drugs on the efficacy of radioiodine treatment (RAI) we retrospectively analyzed 226 patients with GravesÆ disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients without any antithyroid drug (ATD) prior to RAI, 119 patients using propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI. Clinical and laboratory parameters 1 year after RAI defined their clinical status (cured or not cured). High serum free T4 and 131-iodine uptake were negatively related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05). The percentage of cured patients on PTU prior to RAI was 70.2 percent (84/119), while those on MMI was 85.7 percent (42/49), and 84.5 percent (49/58) of those without ATD prior to RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter, RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared to patients with no ATD prior to RAI, we concluded that the previous use of PTU implies in higher failure rates after RAI (OR= 3.13), an effect not observed in patients on MMI (OR= 1.28).

Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in head and neck cancer patients who had normal or mild impaired salivary gland function.

BACKGROUND: Amifostine has a potential role for salivary gland protection in head and neck cancer patients who had radiotherapy. MATERIAL AND METHOD: Sixty-seven head and neck cancer patients were randomized to receive radiotherapy or radiotherapy plus Amifostine. The efficacy of the treatment was determined by a questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC acute/late radiation morbidity scoring criteria, collection of the whole saliva and the 99mTc-pertecnetate scintigraphy of the salivary glands. RESULTS: Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73, the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia from 82% to 39%. The salivary gland function returned to normal at a rate of 36.3% in the Amifostine group versus 9.1% in the control group. CONCLUSION: Amifostine is effective in reducing the incidence and severity of acute mucositis, acute and late xerostomia in head and neck cancer patients.

Some novel approaches for radioprotection and the beneficial effect of natural products.

Due to the increased use of ionizing radiation in various aspects of human life especially in areas pertaining to radiotherapy of cancer, food preservation, agriculture, industry and power generation, there is a need to develop an effective and non-toxic radioprotector. The currently available ones have many drawbacks including high cost, side effects and toxicity. Several novel approaches are on to locate a potent radioprotector. These include mimics of antioxidant enzymes, nitroxides, melatonin, growth factors, gene therapy, hyperthermia apart from natural products. The latter has several advantages since they are non-toxic with proven therapeutic benefits. These can be classified as natural compounds and plant extracts; polyherbal formulations; besides natural and semi-natural compounds of plant origin. A review of the above agents, their efficacy in radioprotection and possible mechanisms responsible has been carried out. As India and many Eastern countries have an enormous heritage of vast natural dietary and time tested medicinal resources it is worth exploring the possibility of developing efficient, economically viable and clinically acceptable radioprotectors for human application from these resources.

Otoproteção da amifostina aos efeitos ototóxicos da cisplatina: estudo em cobaias albinas por emissões otoacústicas produtos de distorção e microscopia eletrônica de varredura

A Cisplatina é uma potente droga antineoplásica, largamente utilizada para o tratamento do câncer, tanto em adultos quanto em crianças. Dentre seus efeitos colaterais, a ototoxicidade se apresenta como um dos mais importantes e leva à perda auditiva irreversível, bilateral, para as altas freqüências (4KHz -8KHz). Estudos têm tentado identificar drogas que, associadas à cisplatina, possam atuar como otoprotetores. Sabe-se que o mecanismo da ototoxicidade pela cisplatina está relacionado a alterações nos mecanismos antioxidantes das células ciliadas, principalmente as células ciliadas externas da cóclea. A amifostina tem conhecida ação antioxidante, com conhecido efeito otoprotetor aos efeitos lesivos da radioterapia. OBJETIVO: Nossa proposta foi avaliar através de emissões otoacústicas, por produtos de distorção (EOAPD) e por microscopia eletrônica de varredura (MEV), a existência de possível efeito otoprotetor da amifostina no tratamento com cisplatina. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: O estudo foi realizado em cobaias albinas, que foram divididas em três grupos: Grupo 1: 6 animais -12 orelhas - cisplatina 8,0 mg/Kg/dia (via intraperitoneal) por três dias; Grupo 2: 6 animais - 12 orelhas - amifostina 100 mg/Kg/ dia (via intraperitoneal) e 90 minutos após, cisplatina 8,0 mg/Kg/dia (via intraperitoneal) por três dias; Grupo 3: 03 animais - 06 orelhas - amifostina 100 mg/Kg/dia (via intraperitoneal) por três dias. RESULTADO: Encontramos EOAPD presentes e células ciliadas externas presentes, sem lesão anatômica a MEV, nos grupos 2 e 3. Concluímos que a amifostina, por sua ação antioxidante, atua como otoprotetor a ototoxicidade pela cisplatina. No entanto, seu uso não é recomendável nos casos de tumores potencialmente curáveis, por não se saber exatamente a influência da cisplatina na eficácia da quimioterapia.

Modelo biológico para evaluar la acción fotoprotectora de un extracto de cordón umbilical humano / Biological model to evaluate the photoprotective action of an extract from human umbilical cord

Se demostró por observación macroscópica e histológica que la aplicación tópica de un extracto de cordón umbilical humano en forma de gel, es capaz de proteger la piel de ratones albinos Balb/C de los efectos perjudiciales producidos por la exposición de estos a una fuente artificial de radiaciones ultravioletas. Se compararon además los resultados obtenidos en este sentido con un fotoprotector de la industria norteamericana, e igualmente se discutieron las posibilidades de usar este modelo biológico para evaluar productos con acción fotoprotectora

Mentha piperita (Linn) leaf extract provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Intestinal protection in mice against radiation injury by M. piperita (1 g/kg body weight/day) was studied from day 1 to day 20 after whole body gamma irradiation (8 Gy). Villus height, goblet cells/villus section, total cells, mitotic cells and dead cells/crypt section in the jejunum are good parameters for the assessment of radiation damage. There was significant decrease in the villus height, number of total cells and mitotic cells/crypt section, whereas goblet cells and dead cells showed significant increase after irradiation. Mentha pretreatment resulted in a significant increase in villus height, total cells and mitotic cells, whereas goblet cells and dead cells showed a significant decrease from respective irradiated controls at each autopsy day. The results suggest that Mentha pretreatment provides protection against radiation induced alterations in intestinal mucosa of Swiss albino mice.

Radioprotective effects of DNA ligands Hoechst-33342 and 33258 in whole body irradiated mice.

Radioprotective effects of bisbenzimidole derived DNA ligands Hoechst-33342 (H-342) and Hoechst-33258 (H-258) have been investigated in whole body irradiated stain-A and Balb/c mice (Co-60 Gamma-ray, absorbed doses of 2.5 to 10 Gy delivered at dose rates of 0.01 to 0.50 Gy/min). Biodistribution of Hoechst dyes (2 or 5 mg/kg, body wt., i.v.) and their effects on cell cycle kinetics in bone marrow were studied by flow cytometry. Protection against radiation-induced chromosomal aberrations, micronuclei formation, alterations in DNA content dispersion, inhibition of erythropoiesis and animal lethality were investigated. Significant amount of DNA bound Hoechst could be observed in liver, intestine, kidney and brain for more than 14 days after its administration, while in the bone marrow cells, a reduction in the bound Hoechst was noticed after 7 days. H-342 significantly reduced the radiation-induced chromosome aberrations mainly due to a decrease in the frequency of acentrics (nearly 30%), while a marginal decrease (10%) in the dicentrics was observed at all the dose rates studied. Both H-342 and H-258 reduced the radiation-induced micronuclei formation in a dose dependent manner (2-10 mg/kg body wt.) and this protective effect was observed up to 6 days after the administration. Neither of the two compounds induced any cytogenetic damage in the bone marrow cells of unirradiated animals nor induced tumours at the doses used here (< 5 mg/kg, body wt. i.v.). Reduction in cytogenetic damage of bone marrow cells led to a faster recovery of erythropoesis as observed by increased PCE/NCE ratio in the peripheral blood erythrocytes of the animals which received Hoechst before irradiation. H-258 (5 mg/kg body wt.) given 18 hr before irradiation reduced radiation-induced animal death (5-9 Gy), while no significant effect was observed at higher doses (10 Gy). However, H-342, which has a higher cell permeability, even at a lower dose (2 mg/kg body wt.) showed significant protection at 10 Gy. The protective effects could be enhanced further, by combining these DNA binding agents with the glucose analogue, 2-deoxy-D-glucose (2-DG) which has been shown earlier to protect bone marrow cells against radiation damage.

Pancitoproteção seletiva: revolução na terapia oncológica / Selective pancytoprotective: revolution on cancer therapy

Amifostina é um agente pancitoprotetor seletivo que protege os teci- dos normais, mas não os tumorais, contra os danos citotóxicos induzidos pela quimioterapia e irradiação ionizante. Trata-se de pró- droga que requer defosforilação pela fosfatase alcalina da membrana celular dos tecidos para formação de seu principal metobólito, o WR- 1065, o qual é imediatamente captado pelos tecidos normais, com resultante citoproteção. A droga é geralmente bem tolerada, exibindo efeitos colaterais moderados e transitórios. É o pancitoprotetor seletivo que reúne o maior banco de dados pré-clínicos.

Amifostine is a selective pancytoprotective agent that protects normal, but not maligmant tissues, from the cytotoxic damage induced by chemotherapy and irradiation therapy. It is a pro- drug that requires dephosphorilation at the tissue site by mem- brane-bound alkaline phosphatase in order to produce its main Amifostine is a selective pancytoprotective agent that protects normal, but not maligmant tissues, from the cytotoxic damage active metabolite, WR-I065, which is immediately taken up by the normal tissues, resulring in cytoprotection. The drug is usually well tolerated, with moderate and transient side-effects. To date, amifostine is the selective pancytoprotective agent with the largest preclinical databases.