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1.
Arch. cardiol. Méx ; 91(2): 229-234, abr.-jun. 2021. tab, graf
Article in Spanish | LILACS | ID: biblio-1248790

ABSTRACT

Resumen Hoy una de las principales causas de mortalidad es el cáncer. La supervivencia en pacientes con cáncer ha incrementado de 1970 (25%) a la actualidad (80%). A raíz de la introducción de las antraciclinas como tratamiento de cáncer desde 1960-1970, más del 60% de los pacientes son tratados con estos agentes; sin embargo, la exposición de quimioterápicos conlleva las enfermedades cardiovasculares como la principal causa de mortalidad en enfermos supervivientes de cáncer en el s. XXI. Hay múltiples factores que incrementan la sensibilidad de cardiotoxicidad inducida por antracíclicos. En 1970 el estándar de oro para la detección de disfunción ventricular era la biopsia endomiocárdica, en forma posterior la detección y manejo de la cardiotoxicidad fue guiada por los síntomas, en 1981 la detección de cardiotoxicidad fue reportada con la determinación de la fracción de expulsión del ventrículo izquierdo (FEVI) por ecocardiografía 2D. En la actualidad el ecocardiograma 3D para FEVI y volúmenes sistólico y diastólico han presentado una alta correlación de los valores obtenidos por resonancia magnética para la evaluación de la función cardiaca. Hoy en día la ecocardiografía strain, strain-rate y speckle tracking se utilizan para determinar la función miocárdica regional y global. Para una valoración integral estos resultados se pueden complementar con biomarcadores cardiacos (troponinas y propéptido natriurético tipo B) y cambios electrocardiográficos. De esta forma se puede detectar insuficiencia cardiaca subclínica y dar un tratamiento oportuno.


Abstract Today one of the main causes of mortality is cancer. Survival in cancer patients has increased from 1970 (25%) to the present (80%). Following the introduction of anthracyclines as a cancer treatment since 1960-70, more than 60% of patients are treated with these agents, although chemotherapeutic exposure leads to cardiovascular diseases as the main cause of mortality in surviving patients. of cancer in the 21st Century. There are multiple factors that increase the sensitivity of anthracyclic-induced cardiotoxicity. In 1970 the gold standard for the detection of ventricular dysfunction was endomyocardial biopsy, subsequently the detection and management of cardiotoxicity was guided by symptoms, in 1981 the detection of cardiotoxicity was reported with the determination of the ejection fraction of the left ventricle (LVEF), by 2D echocardiography. Currently, the 3D echocardiogram for LVEF and systolic and diastolic volumes have presented a high correlation of the values obtained by magnetic resonance imaging for the evaluation of cardiac function. Today strain, strain-rate and speckle tracking echocardiography are used to determine regional and global myocardial function. For a comprehensive assessment, these results can be complemented with cardiac biomarkers (troponins) and electrocardiographic changes. In this way, subclinical heart failure can be detected and timely treatment can be given.


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Young Adult , Echocardiography/methods , Echocardiography, Three-Dimensional/methods , Cardiotoxicity/diagnostic imaging , Heart Failure/diagnosis , Neoplasms/drug therapy , Antineoplastic Agents/toxicity , Heart Failure/etiology , Antineoplastic Agents/therapeutic use
2.
Int. arch. otorhinolaryngol. (Impr.) ; 24(1): 47-52, Jan.-Mar. 2020. graf
Article in English | LILACS | ID: biblio-1090559

ABSTRACT

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.


Subject(s)
Animals , Male , Acetylcysteine/therapeutic use , Free Radical Scavengers/therapeutic use , Cisplatin/toxicity , Oxidative Stress/drug effects , Antineoplastic Agents/toxicity , Acetylcysteine/metabolism , Acetylcysteine/pharmacology , Microscopy, Electron, Scanning , Evoked Potentials, Auditory, Brain Stem , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Fluorescent Antibody Technique , Cisplatin/therapeutic use , Rats, Wistar , Cochlea/anatomy & histology , Cochlea/drug effects , Free Radicals , Glutathione Peroxidase/metabolism , Hearing Loss, Sensorineural/prevention & control
3.
Braz. j. med. biol. res ; 53(11): e10263, 2020. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132488

ABSTRACT

Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.


Subject(s)
Animals , Male , Rabbits , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/prevention & control , Amifostine/therapeutic use , Oxaliplatin , Hyperalgesia/chemically induced , Hyperalgesia/prevention & control , Hyperalgesia/drug therapy , Antineoplastic Agents/toxicity
4.
Evid. actual. práct. ambul ; 23(4): e002101, 2020. ilus
Article in Spanish | LILACS | ID: biblio-1141414

ABSTRACT

Uno de los efectos adversos que generan mayor impacto psicosocial en los pacientes que se someten a quimioterapia es la pérdida de cabello. El uso de los cascos fríos podría representar una alternativa para prevenir la alopecia. Estos dispositivos producen vasoconstricción en los vasos sanguíneos del cuero cabelludo provocando que los quimioterápicos lleguen en menores concentraciones a los folículos pilosos, y por consiguiente, evitando que los citotóxicos alcancen el metabolismo de las células foliculares. Se propone que este proceso permita prevenir la alopecia, aunque existe una preocupación que es la posibilidad de metástasis en cuero cabelludo si la quimioterapia no llega a este tejido. Partiendo de la consulta de una paciente con diagnóstico reciente de cáncer de mama, surge el interrogante si en pacientes en tratamiento con quimioterapia el uso de cascos fríos en comparación con su no utilización, disminuye la caída del cabello y si aumenta el riesgo de metástasis en cuero cabelludo. Luego de realizar una búsqueda, se analizaron los resultados de tres artículos pertinentes. Se concluye que el uso de cascos fríos en pacientes que reciben quimioterapia representaría una opción válida para prevenir la alopecia sin indicios de problemas de seguridad y se realiza una reseña acerca de la disponibilidad de los cascos fríos en Argentina. (AU)


One of the adverse effects that generate greater psychosocial impact in patients undergoing chemotherapy is hair loss. The use of cold caps could represent an alternative to prevent alopecia. These devices produce vasoconstriction in the blood vessels of the scalp, causing chemotherapeutic agents to reach the hair follicles in lower concentrations, and there forepreventing toxins from being metabolized by the follicular cells. Thus, alopecia could be prevented but, there is a concern that is the possibility of metastasis to the scalp if the therapy does not reach this tissue. Based on a consultation of a patient recently diagnosed with breast cancer, the question arises whether in patients undergoing chemotherapy the useof cold caps compared to their non-use reduces hair loss and whether it in creases the risk of metastasis to the scalp. After performing a search, the results of three relevant articles were analyzed. It is concluded that the use of cold helmets in patients receiving chemotherapy would represent a valid option to prevent alopecia without indications of safety problems. Finally, a review is made about the availability of scalp-cooling devices in Argentina.


Subject(s)
Humans , Female , Middle Aged , Alopecia/prevention & control , Head Protective Devices , Hypothermia, Induced/instrumentation , Argentina , Scalp , Breast Neoplasms/complications , Randomized Controlled Trials as Topic , Alopecia/chemically induced , Systematic Reviews as Topic , Neoplasm Metastasis , Antineoplastic Agents/adverse effects , Antineoplastic Agents/toxicity , Antineoplastic Agents/therapeutic use
5.
Braz. j. otorhinolaryngol. (Impr.) ; 85(6): 766-773, Nov.-Dec. 2019. tab, graf
Article in English | LILACS | ID: biblio-1055506

ABSTRACT

Abstract Introduction: Ototoxicity refers to cellular damage or function impairment developing in the inner ear in association with any therapeutic agent or chemical substance, and still represents the principal side-effect restricting the use of cisplatin. Objective: The aim of this study was to perform a biochemical, functional and histopathological investigation of the potential protective effect of eugenol against cisplatin-induced ototoxicity. Methods: The study was performed with 24 female Sprague Dawley rats. Distortion product otoacoustic emissions tests were performed on all animals, which were randomized into four equal groups. A single intraperitoneal dose of 15 mg/kg cisplatin was administered to cisplatin group, while the eugenol group received 100 mg/kg eugenol intraperitoneal for five consecutive days. 100 mg/kg eugenol was administered to cisplatin + eugenol group for 5 days. On the third day, these rats were received a single dose of 15 mg/kg cisplatin. The control group was given 8 mL/kg/day intraperitoneal saline solution for five days. The distortion product otoacoustic emissions test was repeated 24 h after the final drug administration. All animals were sacrificed, and the cochleas were subsequently used for biochemical and histopathological examinations. Results: Cisplatin caused oxidative stress in the cochlea, impaired the cochlear structure and significantly reduced signal noise ratio levels. Administration of eugenol together with cisplatin reversed these effects and provided functional, biochemical and histopathological protection. Conclusion: The study findings represent the first indication in the literature that eugenol may protect against ototoxicity by raising levels of antioxidant enzymes and lowering those of oxidant parameters.


Resumo Introdução: A ototoxicidade refere-se ao dano celular ou comprometimento da função da orelha interna associado a qualquer agente terapêutico ou substância química e ainda representa o principal efeito colateral que restringe o uso da cisplatina. Objetivo: O objetivo deste estudo foi realizar uma investigação bioquímica, funcional e histopatológica do potencial efeito protetor do eugenol contra a ototoxicidade induzida pela cisplatina. Método: O estudo foi realizado com 24 ratos fêmeas Sprague Dawley. Testes de emissões otoacústicas por produto de distorção foram realizados em todos os animais, os quais foram randomizados em quatro grupos iguais. Uma única dose intraperitoneal de 15 mg/kg de cisplatina foi administrada ao grupo cisplatina, enquanto o grupo eugenol recebeu 100 mg/kg de eugenol intraperitoneal por cinco dias consecutivos. Foram administrados 100 mg/kg de eugenol ao grupo cisplatina + eugenol durante 5 dias. No terceiro dia, estes ratos receberam uma dose única de 15 mg/kg de cisplatina. O grupo controle recebeu 8 mL/kg/dia de solução salina intraperitoneal por cinco dias. O teste de emissões otoacústicas por produto de distorção foi repetido 24 horas após a administração final do medicamento. Todos os animais foram sacrificados e as cócleas foram posteriormente utilizadas para exames bioquímicos e histopatológicos. Resultados: A cisplatina causou estresse oxidativo na cóclea, prejudicou a estrutura coclear e reduziu significativamente os níveis da relação sinal/ruído. A administração de eugenol juntamente com a cisplatina reverteu esses efeitos e forneceu proteção funcional, bioquímica e histopatológica. Conclusão: Os achados do estudo representam a primeira indicação na literatura de que o eugenol pode proteger contra a ototoxicidade, eleva os níveis de enzimas antioxidantes e diminui os níveis dos parâmetros oxidantes.


Subject(s)
Animals , Female , Rats , Eugenol/therapeutic use , Cisplatin/toxicity , Hearing Loss/prevention & control , Antineoplastic Agents/toxicity , Antioxidants/therapeutic use , Rats, Sprague-Dawley , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/drug effects , Cochlea/pathology , Disease Models, Animal , Hearing Loss/chemically induced
6.
Int. j. morphol ; 37(2): 509-514, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002252

ABSTRACT

Cisplatin is an antineoplastic agent with neuropathy as one of its major side effect. However, effective treatment is lacking. Increasing evidence suggests that cisplatin might damage nerve capillaries leading to impaired functions of blood-nerve barrier (BNB) and neuropathy. This study was aimed to examine the effects of cisplatin on pericytes. Rats were either treated with intraperitoneal injection of cisplatin 2 mg/kg twice a week for five continuous weeks. Cisplatin-treated rats showed reduced body weight, thermal hypoalgesia and slow sciatic motor nerve conduction velocity, indicating neuropathy. The density of pericytes in the distal sciatic nerves determined by immunohistochemistry to desmin was significantly reduced in the cisplatin compared with that of the control groups. Electron microscopic analysis demonstrated the detachment of pericytes from endothelial cells including the disruption of shared basement membrane in the sciatic nerves from cisplatin-treated rats. These data indicate the pericyte loss and detachment caused by cisplatin. Future studies of the BNB components and functions after cisplatin treatment are needed and will be essential for the development of effective treatments against cisplatin-induced neuropathy.


El cisplatino es un agente antineoplásico y presenta como uno de sus principales efectos secundarios, la neuropatía. Sin embargo, falta un tratamiento eficaz. La creciente evidencia sugiere que el cisplatino podría dañar los capilares nerviosos, lo que puede provocar una alteración de las funciones de la barrera hematoencefálica (BHE) y neuropatía. Este estudio tuvo como objetivo examinar los efectos del cisplatino en los pericitos. Las ratas se trataron con inyección intraperitoneal de cisplatino (2 mg/kg) dos veces por semana durante 5 semanas seguidas. Las ratas tratadas con cisplatino mostraron una reducción del peso corporal, hipoalgesia térmica y una velocidad de conducción del nervio ciático lenta, lo que indicaría neuropatía. La densidad de los pericitos en los nervios ciáticos distales determinada por inmunohistoquímica para desmina se redujo significativamente en el grupo cisplatino en comparación con la de los grupos controles. El análisis al microscopio electrónico demostró el desprendimiento de pericitos de las células endoteliales, incluida la ruptura de la membrana basal compartida en los nervios ciáticos de ratas tratadas con cisplatino. Estos datos indican la pérdida de pericitos y el desprendimiento causado por el cisplatino. Se necesitan estudios futuros de los componentes y funciones del BHE después del tratamiento con cisplatino y serán esenciales para el desarrollo de tratamientos efectivos contra la neuropatía inducida por el cisplatino.


Subject(s)
Animals , Male , Rats , Cisplatin/toxicity , Pericytes/drug effects , Nervous System Diseases/pathology , Antineoplastic Agents/toxicity , Body Weight/drug effects , Immunohistochemistry , Rats, Wistar , Pericytes/pathology , Microscopy, Electron, Transmission , Nervous System Diseases/chemically induced
7.
Braz. j. otorhinolaryngol. (Impr.) ; 85(1): 55-62, Jan.-Feb. 2019. tab, graf
Article in English | LILACS | ID: biblio-984047

ABSTRACT

Abstract Introduction: Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage. Objective: We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress. Methods: Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day. Results: The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress. Conclusion: The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.


Resumo Introdução: A cisplatina é um dos principais agentes quimioterápicos utilizados para o tratamento de muitos tipos de câncer. No entanto, a ototoxicidade, um dos efeitos colaterais mais graves da cisplatina, restringe seu uso. Objetivo: Nosso objetivo foi investigar os efeitos protetores do extrato de uva-do-monte contra a ototoxicidade induzida por cisplatina, avaliar o dano auditivo e histopatológico coclear e medir os parâmetros bioquímicos afetados pelo estresse oxidativo. Método: Foram incluídos no estudo 48 ratos machos após teste de emissão otoacústica evocada por produto de distorção para confirmar que seus níveis de audição eram normais. Os ratos foram divididos aleatoriamente em seis grupos: o grupo controle, o grupo simulado, o que recebeu apenas extrato de uva-do-monte, o que recebeu apenas cisplatina, o que recebeu cisplatina + 100 mg de extrato de uva-do-monte e o que recebeu cisplatina + 200 mg de extrato de uva-do-monte, respectivamente. A investigação audiológica foi feita através do teste de emissão otoacústica de produto de distorção no início e no oitavo dia do estudo. As amostras de sangue cardíaco foram coletadas para análise bioquímica e os ratos foram sacrificados para obtenção de espécimes histopatológicos cocleares no oitavo dia. Resultados: Os resultados revelaram que o extrato de uva-do-monte protege a audição contra a ototoxicidade induzida por cisplatina, independentemente da dose. No entanto, são necessárias doses elevadas do extrato para evitar a degeneração histopatológica e o estresse oxidativo. Conclusão: Os resultados obtidos neste estudo mostram que o extrato de uva-do-monte tem um efeito protetor contra a ototoxicidade induzida por cisplatina.


Subject(s)
Animals , Male , Cisplatin/toxicity , Cochlea/drug effects , Protective Agents/therapeutic use , Hearing/drug effects , Anthocyanins/therapeutic use , Antineoplastic Agents/toxicity , Reference Values , Acoustic Stimulation , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/pathology , Oxidative Stress/drug effects , Antioxidants/therapeutic use
8.
Int. j. morphol ; 36(2): 519-522, jun. 2018. graf
Article in English | LILACS | ID: biblio-954147

ABSTRACT

Methotrexate drug is commonly used to treat cancer; it is known to cause reproductive damage. Thymoquinone, as a natural component of herbs has many healthy benefits shown in researches. The present study aimed to investigate probable therapeutic effects of Thymoquinone against Methotrexate-induced damage on sperm parameters in mice. In this experimental study, 30 male mice (25-30 g) were divided into five groups of six in each group. The mice were received normal saline (control group), Methotrexate (20 mg/kg), Methotrexate (20 mg/kg) + Thymoquinone (2, 10 and 20 mg/kg) by intraperitoneal injection. On the day after the last injection, the sperm parameters including motility, viability and count of sperms were assessed. Data analysis was performed using one-way ANOVA followed by Tukey test. Methotrexate alone showed a significant reduction in sperm parameters compared to the control group (P=0.00). In groups treated with Methotrexate and Thymoquinone, sperm parameters (motility ,viability, count sperm) did not show any significant differences with control group (P=0.00). Thymoquinone, as a potent antioxidant, could compensate for the toxicity induced by Methotrexate. These medical trends may be useful for diminishing the side effects of Methotrexate on the male reproductive system.


El metotrexato es un fármaco utilizado comúnmente para tratar el cáncer pero además causa daño en los órganos reproductivos. Durante las investigaciones se ha demostrado que la timoquinona, un componente natural de las hierbas, tiene numerosos beneficios. El objetivo del estudio fue investigar el probable efecto terapéutico de la timoquinona contra el daño inducido por metotrexato, en los parámetros espermáticos en ratones. En este estudio experimental, se dividieron 30 ratones machos (25-30 g) en cinco grupos de seis en cada uno. Los ratones recibieron solución salina normal (grupo control), metotrexato (20 mg / kg), metotrexato (20 mg / kg) + timoquinona (2, 10 y 20 mg / kg) por inyección intraperitoneal. El día después de la última inyección, se evaluaron los parámetros espermáticos, incluida la motilidad, la viabilidad y el recuento de espermatozoides. El análisis de los datos se realizó utilizando test de ANOVA seguido de la prueba de Tukey. Durante el uso exclusivo de metotrexato se observó una reducción significativa en los parámetros espermáticos en comparación con el grupo control (P = 0.00). En los grupos tratados con metotrexato y timoquinona, los parámetros espermáticos (motilidad, viabilidad, conteo de espermatozoides) no mostraron diferencias significativas con el grupo control (P = 0.00). Como potente antioxidante, la timoquinona podría compensar la toxicidad inducida por metotrexato. Estas tendencias médicas pueden ser útiles para disminuir los efectos secundarios de metotrexato en el sistema reproductivo masculino.


Subject(s)
Animals , Male , Mice , Spermatozoa/drug effects , Methotrexate/toxicity , Benzoquinones/administration & dosage , Antineoplastic Agents/toxicity , Mice, Inbred BALB C
9.
Int. j. morphol ; 36(1): 140-144, Mar. 2018. tab, graf
Article in English | LILACS | ID: biblio-893201

ABSTRACT

SUMMARY: Toxic effects of anti-cancer and other drugs on the normal tissues could be reduced by the herbal plants and their fractions. This study investigated the protective effect of Tribulus terrestris (TT) on Cisplatin- induced cytotoxicity germ cell apoptosis in male mice. In this experimental study, thirty male Balb/c mice were divided randomly into 5 groups (n=6). A single dose of Cisplatin (5.5 mg/kg) and differ-ent concentrations of Tribulus terrestris were administrated for 14 consecutive days. Reverse transcription polymerase chain reaction (RT-PCR) of apoptosis-re-lated genes was performed with RNA extracted from testes of the mice. Statistical analysis was done using one-way ANOVA. In the Cisplatin group, there was a significant increase in mRNA expression of p53 (P=0.008), bax (P=0.004) and the ratio of bax/Bcl-2 (P=0.000), whereas there was an decrease in the expression of Bcl-2 (P=0.003), as compared to control group. In Cis+TT groups, the data showed that different concentrations of TT could improve the harmful effects caused by the Cisplatin. The best protective effects were achieved in Cis+TT (300 mg/kg). Tribulus terrestris protects testicular germ cell against Cisplatin induced apoptosis by affecting related genes regulation.


RESUMEN: Los efectos tóxicos en los tejidos normales, de los medicamentos contra el cáncer al igual que otras medicamentos podrían mejorar con el uso de plantas medicinales y hierbas. Este estudio investigó el efecto protector de Tribulus terrestris (TT) sobre la apoptosis de células germinales por citotoxicidad inducida por cisplatino en ratones machos. En este estudio se dividieron treinta ratones Balb/c macho aleatoriamente en 5 grupos (n = 6). Se administró una sola dosis de cisplatino (5,5 mg / kg) y diferentes concentraciones de Tribulus terrestris durante 14 días consecutivos. La reacción en cadena de la polimerasa de transcripción reversa de los genes relacionados con la apoptosis, se realizó con ARN extraído de los testículos de los ratones. El análisis estadístico se realizó usando ANOVA de una vía. En el grupo cisplatino, hubo un aumento significativo en la expresión de mRNA de p53 (P = 0,008), bax (P = 0,004) y la relación de bax / Bcl-2 (P = 0.000), mientras que hubo una disminución en la expresión de Bcl-2 (P = 0,003), en comparación con el grupo control. En los grupos Cis + TT, los datos mostraron que las diferentes concentraciones de TT podrían mejorar los efectos nocivos causados por el cisplatino. Los mejores efectos protectores se lograron en Cis + TT (300 mg / kg). Tribulus terrestris protege las células germinales testiculares contra la apoptosis inducida por cisplatino al afectar la regulación de los genes relacionados.


Subject(s)
Animals , Male , Mice , Apoptosis/drug effects , Cisplatin/toxicity , Germ Cells/drug effects , Plant Extracts/administration & dosage , Tribulus , Antineoplastic Agents/toxicity , Apoptosis/genetics , Mice, Inbred BALB C , Reverse Transcriptase Polymerase Chain Reaction
10.
Acta cir. bras ; 32(10): 873-880, Oct. 2017. graf
Article in English | LILACS | ID: biblio-886168

ABSTRACT

Abstract Purpose: To evaluate the ability of dexamethasone to protect against cisplatin (CDDP)-induced ototoxicity. Methods: Male Wistar rats were divided into the following three groups: 1) Control (C): 6 animals received intraperitoneal (IP) saline solution, 8 ml/kg/day for four days; 2) C + CDDP: 11 animals received 8 ml/kg/day of IP saline and, 90 min after saline administration, 8 mg/kg/day of IP CDDP for four days; and 3) DEXA15 + CDDP: 11 animals received IP dexamethasone 15 mg/kg/day and, 90 min after dexamethasone administration, received 8 mg/kg/day of IP CDDP for four days. Results: It was found that dexamethasone did not protect against weight loss in CDDP-exposed animals. The mortality rate was comparable with that previously reported in the literature. The auditory threshold of animals in the DEXA15 + CDDP group was not significantly altered after exposure to CDDP. The stria vascularis of animals in the DEXA15 + CDDP group was partially preserved after CDDP exposure. Conclusions: Dexamethasone at the dose of 15 mg/kg/day partially protected against CDDP-induced ototoxicity, based on functional evaluation by brainstem evoked response audiontry (BERA) and morphological evaluation by optical microscopy. However, dexamethasone did not protect against systemic toxicity.


Subject(s)
Animals , Male , Rats , Auditory Threshold/drug effects , Dexamethasone/therapeutic use , Cisplatin/toxicity , Cochlea/drug effects , Protective Agents/therapeutic use , Antineoplastic Agents/toxicity , Rats, Wistar , Models, Animal
11.
Rev. bras. cancerol ; 62(2): 137-145, abr.-jun. 2016.
Article in Portuguese | LILACS | ID: biblio-847359

ABSTRACT

Introdução: A exposição ocupacional às propriedades citotóxicas da quimioterapia implica em riscos à saúde desses profissionais, podendo causar alterações agudas ou crônicas oriundas do manuseio dos agentes antineoplásicos em longo prazo. Objetivo: Identificar o conhecimento de enfermeiros a respeito das medidas de biossegurança para administração de quimioterapia. Método: Estudo descritivo transversal com enfermeiros de um hospital geral. A coleta de dados ocorreu por meio de questionário autoaplicado e os dados foram analisados através de medidas de tendência central, dispersão e correlações. Resultados: Trinta enfermeiros participaram do estudo e 23 deles informaram nunca ter recebido capacitação para trabalhar com quimioterápicos. O escore médio de conhecimento dos participantes foi 27,6 de um total possível de 37 pontos. Conclusão: Os enfermeiros da instituição pesquisada apresentam conhecimento parcialmente adequado às recomendações de biossegurança. A identificação de lacunas no conhecimento pode orientar o desenvolvimento de protocolos e programas de capacitação, aspecto fundamental atualmente, haja vista o elevado número de pacientes com câncer internados em unidades de clínica médica em hospitais gerais.


Introduction: Occupational exposure to the cytotoxic properties of chemotherapy entails risks to professionals' health and may cause acute or chronic changes arising from the long-term handling of antineoplastic agents. Objective: To identify the nurses' knowledge of the biosecurity measures for administering chemotherapy. Method: Cross-sectional descriptive study with nurses at a general hospital. The data were collected through a self-applied questionnaire and the data were analyzed using measures of central tendency, dispersion, and correlation. Results: Thirty nurses were enrolled in this study and 23 reported they had never received training on working with chemotherapy drugs. The average score of the subjects was 27.6 out of a possible 37 points. Conclusion: The nurses of the institution investigated have partially adequate knowledge of biosafety recommendations. Identifying gaps in knowledge can guide the development of protocols and training programs, a fundamental aspect, given the high number of cancer patients admitted to medical units in general hospitals.


Introducción: La exposición ocupacional a las propiedades citotóxicas de la quimioterapia implica riesgos para la salud de estos profesionales, puede causar cambios agudos o crónicos derivados de la manipulación de agentes antineoplásicos a largo plazo. Objetivo: Identificar los conocimientos de los enfermeros acerca de las medidas de bioseguridad para administración de la quimioterapia. Método: Estudio descriptivo transversal, con enfermeros de un hospital general. Los datos fueron recolectados a través cuestionario autoadministrado y se analizaron los datos utilizando medidas de tendencia central, dispersión y correlación. Resultados: Treinta enfermeros participaron en el estudio, 23 de ellos informaron que nunca recibieron capacitación para trabajar con agentes quimioterapéuticos. La puntuación media de los participantes fue de 27,6 de un máximo de 37 puntos. Conclusión: Los enfermeros de la institución investigada tienen conocimiento parcialmente adecuado a las recomendaciones de bioseguridad. La identificación de lagunas en el conocimiento puede guiar el desarrollo de protocolos y programas de formación, un aspecto fundamental en la actualidad visto teniendo en cuenta elevado número de pacientes con cáncer ingresados en unidades médicas en los hospitales generales.


Subject(s)
Humans , Male , Female , Antineoplastic Agents/toxicity , Nurses , Occupational Risks , Cross-Sectional Studies , Epidemiology, Descriptive , /statistics & numerical data , Occupational Exposure/statistics & numerical data
12.
Acta cir. bras ; 31(4): 271-277, Apr. 2016. tab, graf
Article in English | LILACS | ID: lil-781332

ABSTRACT

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.


Subject(s)
Animals , Male , Benzoquinones/pharmacology , Cisplatin/toxicity , Cardiomyopathies/chemically induced , Cardiomyopathies/prevention & control , Antineoplastic Agents/toxicity , Antioxidants/pharmacology , Reference Values , Time Factors , Immunohistochemistry , Random Allocation , Reproducibility of Results , Benzoquinones/therapeutic use , Treatment Outcome , Rats, Wistar , Apoptosis/drug effects , Oxidative Stress/drug effects , Proto-Oncogene Proteins c-bcl-2/analysis , Proto-Oncogene Proteins c-bcl-2/drug effects , Myocytes, Cardiac/drug effects , Cardiotoxicity/etiology , Cardiotoxicity/pathology , Cardiotoxicity/prevention & control , Heart/drug effects , Cardiomyopathies/pathology , Myocardium/pathology , Antioxidants/therapeutic use
13.
Article in English | WPRIM | ID: wpr-34240

ABSTRACT

To investigate the function and regulation mechanism of ATP-binding cassette, subfamily G, member 2 (ABCG2) in retinoblastoma cancer stem cells (RCSCs), a long-term culture of RCSCs from WERI-Rb1 cell line was successfully established based on the high expression level of ABCG2 on the surface of RCSCs. To further explore the molecular mechanism of ABCG2 on RCSCs, a microRNA that specifically targets ABCG2 was predicted. Subsequently, miR-3163 was selected and confirmed as the ABCG2-regulating microRNA. Overexpression of miR-3163 led to a significant decrease in ABCG2 expression. Additionally, ABCG2 loss-of-function induced anti-proliferation and apoptosis-promoting functions in RCSCs, and multidrug resistance to cisplatin, carboplatin, vincristine, doxorubicin, and etoposide was greatly improved in these cells. Our data suggest that miR-3163 has a significant impact on ABCG2 expression and can influence proliferation, apoptosis, and drug resistance in RCSCs. This work may provide new therapeutic targets for retinoblastoma.


Subject(s)
3' Untranslated Regions , ATP Binding Cassette Transporter, Subfamily G, Member 2/antagonists & inhibitors , Antagomirs/metabolism , Antineoplastic Agents/toxicity , Apoptosis/drug effects , Base Sequence , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/drug effects , Gene Silencing , Humans , MicroRNAs/antagonists & inhibitors , Neoplasm Proteins/antagonists & inhibitors , Neoplastic Stem Cells/metabolism , Retinoblastoma/metabolism , Sequence Alignment , Transfection
14.
Acta cir. bras ; 30(6): 394-400, 06/2015. tab, graf
Article in English | LILACS | ID: lil-749642

ABSTRACT

PURPOSE: To evaluate the central nervous system toxicity of cisplatin and neuroprotective effect of selenium. METHODS: Twenty-one male Wistar albino rats were divided into three groups: control (C), cisplatin (CS), cisplatin and selenium (CSE, n=7 in each group). Cisplatin (12 mg/kg/day, i.p.) was administered to CS and CSE groups for three days. Furthermore, CSE group received 3mg/kg/day (twice-a-day as 1.5 mg/kg) selenium via oral gavage five days before cisplatin injection and continued for 11 consecutive days. The same volumes of saline were administered to C group intraperitoneally and orally at same time. RESULTS: Heterochromatic and vacuolated neurons and dilated capillary vessels in the brain were observed in the histochemical examinations of cisplatin treated group. Rats that were given a dose of 3mg/kg/day selenium decreased the cisplatin induced histopathological changes in the brain, indicating a protective effect. In addition, cytoplasmic staining of the cell for bcl-2, both cytoplasmic and nuclear staining for bax were determined to be positive in the all groups. Bax positive cells were increased in the CS group compared to C group, in contrast to decreased bcl-2 positivity. CONCLUSION: Selenium limited apototic activity and histological changes due to the cisplatin related central neurotoxicity. .


Subject(s)
Animals , Male , Antineoplastic Agents/toxicity , Antioxidants/pharmacology , Brain/drug effects , Cisplatin/toxicity , Neurons/drug effects , Selenium/pharmacology , Apoptosis/drug effects , Brain/pathology , Immunohistochemistry , Models, Animal , Neuroprotective Agents/pharmacology , Rats, Wistar , Reproducibility of Results , Time Factors
15.
Int. j. morphol ; 33(1): 279-284, Mar. 2015. ilus
Article in English | LILACS | ID: lil-743798

ABSTRACT

Cisplatin is an anti-cancer drug used in chemotherapy. One of the limiting side effects of cisplatin is decreasing genital gland function, azoospermia and oligospermia. Tribulus terrestris (TT) has been used as an aphrodisiac. The present study amid to investigate protective effect of TT hydroalcoholic extract against cisplatin-induced apoptosis on testis in mice. Male adult mice (n=30) were divided into control and 4 experimental groups (n=6). Control group received saline, first experimental group received cisplatin (5.5 mg/kg) and other three experimental group received cisplatin (5.5 mg/kg) and different doses of hydroalcoholic extact of TT (100, 300 and 500 mg/kg/i.p) respectively. Day after the last injection, histopathology and histomorphic analysis and also TUNEL assay on mice testis were performed. Weights of body and testis, seminiferous tubules diameter and apoptotic index were assessed. Data analysis was performed using one-way ANOVA followed by Tukeys' test. The results showed that cisplatin lead to a reduction in the weight of body and testes, and significantly increased apoptotic index compared to the control group (P<0.001), while in treated groups with TT, the weights of body and testis and seminiferous tubules diameter were significantly higher compared with cisplatin group (P<0.001), but apoptotic index did not show significant differences. The study demonstrates that extract of TT could protective effect of on cisplatin-induced apoptosis of testis and seminiferous tubules diameter that may be related to the presence of antioxidant components acting via a multitude of central and peripheral mechanisms.


El cisplatino es un medicamento anticancerígeno utilizado en tratamientos de quimioterapia. Uno de los efectos secundarios que limitan el uso del cisplatino es la disminución en la función de la glándula genital, provocando azoospermia y oligospermia. El Tribulus terrestris (TT) se ha utilizado como un afrodisíaco. El objetivo fue investigar el efecto protector del extracto hidroalcohólico de TT contra la apoptosis inducida por el cisplatino en los testículos de ratones. Ratones machos adultos (n=30) fueron divididos en un grupo control y cuatro grupos experimentales (n=6). Al grupo control se le administró una solución salina, mientras que el primer grupo experimental recibió cisplatino (5,5 mg/kg) y los tres restantes recibieron cisplatino (5,5 mg/kg) con diferentes dosis del extracto hidroalcohólico de TT (100, 300 y 500 mg/kg/ip), respectivamente. El día posterior a la última inyección, se realizaron análisis histopatológicos y morfométricos, junto al ensayo TUNEL, de los testículos de los ratones. Se registró el peso corporal y testicular de cada ratón, así como el diámetro de los túbulos seminíferos e índice de apoptosis. Los datos fueron analizados mediante ANOVA de una vía, seguida de la prueba de Tukey. El cisplatino provocó una reducción del peso corporal y testicular, y un aumento del índice de apoptosis, que fue significativo en comparación con el grupo control (P<0,001), mientras que en los grupos tratados con TT, el peso corporal y testicular, junto al diámetro de los túbulos seminíferos fueron significativamente mayores en comparación con el grupo tratado con cisplatino (P<0,001), sin embargo, el índice de apoptosis no mostró diferencias significativas. El estudio demuestra que el extracto de TT podría poseer un efecto protector de la apoptosis inducida por cisplatino sobre los testículos, así como en el diámetro de los túbulos seminíferos, lo que podría relacionarse con la presencia de componentes antioxidantes que actúan a través de diversos mecanismos, centrales y periféricos.


Subject(s)
Animals , Male , Mice , Testis/drug effects , Plant Extracts/pharmacology , Cisplatin/toxicity , Apoptosis/drug effects , Tribulus , Seminiferous Tubules/drug effects , Analysis of Variance , Protective Agents/pharmacology , In Situ Nick-End Labeling , Mice, Inbred BALB C , Antineoplastic Agents/toxicity
16.
Braz. dent. j ; 25(6): 528-531, Nov-Dec/2014. tab
Article in English | LILACS | ID: lil-732250

ABSTRACT

This study aimed to evaluate the influence of epigallocatechin-3-gallate (EGCG) incorporation on the physicochemical properties of a methacrylate-based dental adhesive. EGCG was added to Adper Easy One (3M-ESPE) except in control group, to obtain concentrations of 0.01% w/w and 0.1% w/w of EGCG-doped adhesives. For water sorption (WS) and solubility (SL) surveys, resin discs were assayed following ISO recommendations (n=10). The degree of conversion (DC) was analyzed by FTIR whereas flexural strength (FS) was tested by three-point bending with bar specimens (n=10). Data were subjected to one-way ANOVA and Tukey's test (p<0.05). No significant difference in the DC, WS and FS were found between the different concentrations of EGCG (p>0.05). Adhesives containing 0.1% or 0.01% of EGCC demonstrated similar values of SL (p>0.05) and higher than those found for adhesive without EGCC (p<0.05). In conclusion, the addition of EGCC to adhesive reduced the solubility without affecting the other evaluated properties.


Esse estudo teve como objetivo avaliar a influência da incorporação de epigalocatequina-3-galato (EGCG) nas propriedades físico-químicas de um sistema adesivo à base de metacrilato. O EGCG foi adicionado ao Adper Easy One (3M-ESPE), exceto para o grupo controle, para a obtenção das concentrações de 0,01% e 0,1% p/p. No ensaio de sorção (S) e solubilidade (SL), foram confeccionados discos de resina de acordo com as recomendações da ISO (n=10). O grau de conversão (GC) foi analisado através de FTIR, enquanto a resistência flexural (RF) foi avaliada em teste de flexão de três pontos com espécimes em forma de barra (n=10). Os dados foram submetidos à Análise de Variância a um critério e teste de Tukey (p<0,05). Não houve diferença significativa entre as concentrações de EGCG testadas no GC, SL e RF (p>0,05). Adesivos contendo EGCG a 0,1% ou 0,01% apresentaram valores similares de SL (p>0,05) e maiores do que os valores obtidos pelo adesivo não incorporado por EGCG. Conclui-se que a adição de EGCG ao adesivo reduziu a solubilidade sem afetar as outras propriedades avaliadas.


Subject(s)
Animals , Female , Rats , Antineoplastic Agents/pharmacology , Floxuridine/pharmacology , Administration, Rectal , Antineoplastic Agents/adverse effects , Antineoplastic Agents/toxicity , Floxuridine/administration & dosage , Floxuridine/toxicity , Leukocyte Count , Neoplasms, Experimental/drug therapy , Platelet Count
17.
Braz. dent. j ; 25(6): 472-478, Nov-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-732254

ABSTRACT

To evaluate the microtensile bond strength (µTBS) of a fluoride-containing adhesive system submitted to a pH-cycling and storage time regimen for primary outcomes. As secondary outcomes the fluoride released amount was evaluated. Twelve dentin surfaces from sound third molar were divided into 2 groups according to adhesive systems: Clearfil SE Protect (PB) and Clearfil SE Bond (SE). Sticks obtained (1.0 mm2) from teeth were randomly divided into 3 subgroups according to storage regimen model: immediate (24h); 5-month deionized water (W); and pH-cycling model (C). All sticks were tested for µTBS in a universal testing machine. Fluoride concentration was obtained from 1-4 days and 30-day in W and 1-4 days in demineralization (DE)/remineralization (RE) solutions from C, using a fluoride-specific electrode. µTBS and fluoride released data were, respectively, submitted to ANOVA in a split plot design and Tukey, and Friedman' tests (a=0.05). There was no significant interaction between adhesive system and storage regimen for µTBS. W showed the lowest µTBS values. There was no significant difference between 24 h and C models for µTBS. There was no significant difference between adhesive systems. Failure mode was predominantly cohesive within composite for the 24 h and W, for the C group it was mixed for SE and cohesive within composite for PB adhesive system. Fluoride concentrations in the DE/RE solutions were less than 0.03125 ppm and not detected in W. In conclusion, the fluoride-containing adhesive system performed similarly to the regular one. Hydrolytic degradation is the main problem with both adhesive systems, regardless of fluoride contents.


O objetivo principal desse estudo foi avaliar a resistência de união à microtração de dois sistemas adesivos (com e sem flúor) após a ciclagem de pH e armazenagem em água deionizada. A quantidade de flúor liberada foi avaliada secundariamente. Doze terceiros molares hígidos foram separados em 2 grupos de acordo com o sistema adesivo: Clearfil SE Protect - com flúor (PB) e Clearfil SE Bond - sem flúor (SE). Os palitos (1 mm2) obtidos do mesmo dente foram aleatoriamente divididos em 3 subgrupos de acordo com o meio de armazenagem: em água deionizada por 24h ou 5 meses e ciclagem de pH. Os palitos foram tracionados em uma máquina de ensaio universal a 0,5 mm/min. A concentração de flúor foi analisada em água deionizada (1-4 dias e 30 dias) e na solução remineralizadora e desmineralizadora (1-4 dias) usando um eletrodo específico. Os dados de resistência de união e liberação de flúor foram, respectivamente, submetidos à Análise de Variância em esquema de parcela subdividida e ao teste de Friedman (a=0,05). Não houve nenhuma interação significativa na resistência de união entre os sistemas adesivos e os meios de armazenagem. Os menores valores de resistência de união à microtração foram encontrados para os palitos armazenados em água deionizada. Não houve nenhuma diferença significativa nos valores de resistência de união após 24h e ciclagem de pH. Nenhuma diferença significativa na resistência de união foi observada entre os 2 sistemas adesivos. O modo de falha foi predominantemente coesivo em compósito para os grupos armazenados em água por 24h ou 5 meses para ambos os sistemas adesivos. No grupo submetido à ciclagem, a falha foi mista para o SE e coesiva em compósito para o PB. A concentração de flúor nas soluções DE/RE foi menor que 0,03125 ppm e não detectada em água deionizada. Concluindo, o sistema adesivo com flúor (PB) apresentou performance similar ao sistema adesivo sem flúor (SE). A degradação hidrolítica foi o principal fator para ambos os sistemas adesivos, independente da adição de flúor.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antineoplastic Agents/administration & dosage , Floxuridine/administration & dosage , Antineoplastic Agents/toxicity , Drug Administration Schedule , Drug Evaluation , Drug Tolerance , Floxuridine/toxicity , Isomerism , Neoplasms/drug therapy
18.
Salud pública Méx ; 56(5): 519-527, sep.-oct. 2014. ilus, tab
Article in Spanish | LILACS | ID: lil-733325

ABSTRACT

Objetivo. Explorar las necesidades de información y consejería de un grupo de mujeres mexicanas al utilizar la prueba de virus de papiloma humano (VPH). Material y métodos. En 2011, se realizaron 24 entrevistas semiestructuradas a mujeres que recibieron el resultado de una prueba de VPH, en dos municipios del estado de Michoacán. El análisis cualitativo de las entrevistas se realizó con las técnicas de la comparación constante. Resultados. Durante el tamizaje, las mujeres recibieron escasa consejería; experimentaron angustia y confusión. Las usuarias de la prueba se mostraron interesadas en recibir información sobre el VPH y el cáncer cervical, el significado de sus resultados, los pasos que habrían de realizar en la atención, apoyo emocional e información vinculada con la transmisión sexual de VPH. Conclusiones. Se requiere diseñar e implementar políticas para impartir educación para la salud y consejería, a la par de la realización de pruebas de VPH.


Objective. To explore the information and counseling needs of a group of Mexican women during use of the HPV test. Materials and methods. In 2011, 24 semistructured interviews were done with women upon receiving HPV test results in two municipalities in the state of Michoacan. Qualitative analysis of the interviews was done using constant comparison techniques. Results. During their use of screening services women received limited counseling; they felt anguish and confusion. Women were interested in receiving information and advice on HPV and cervical cancer, the meaning of test result, next steps to be taken in their healthcare use as well as information and emotional support related to the sexual transmission of HPV. Conclusions. The design and implementation of policies are needed which instigate health education and counseling in conjunction with HPV testing.


Subject(s)
Animals , Mice , Antineoplastic Agents/toxicity , Enzyme Inhibitors/pharmacology , Floxuridine/toxicity , Intestines/drug effects , Thymidine Phosphorylase/antagonists & inhibitors , Uracil/analogs & derivatives , Administration, Oral , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Body Weight , Carcinoma, Lewis Lung/drug therapy , Drug Synergism , Floxuridine/administration & dosage , Floxuridine/therapeutic use , Isomerism , Uracil/administration & dosage , Uracil/pharmacology
19.
J. bras. nefrol ; 36(3): 280-288, Jul-Sep/2014. tab, graf
Article in Portuguese | LILACS | ID: lil-725501

ABSTRACT

Introdução: A injúria renal aguda (IRA) em pacientes que recebem a cisplatina é comum, portanto, a avaliação da função renal em pacientes utilizando drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL) na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP) que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 horas antes da cisplatina, 24 horas após a infusão, 48 horas após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos). Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal. Os níveis de NGAL podem estar elevados em relação aos níveis basais, mesmo antes da utilização da cisplatina. .


Introduction: Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. Objective: To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. Methods: We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 hours before cisplatin, 24 hours after infusion, 48 hours after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). Results: AKI was observed in 78% of patients. There was increase in creatinine, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. Conclusion: AKI was noted in 78% of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin. .


Subject(s)
Female , Humans , Male , Middle Aged , Acute Kidney Injury/chemically induced , Acute Kidney Injury/urine , Acute-Phase Proteins/urine , Antineoplastic Agents/toxicity , Cisplatin/toxicity , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/urine , Lipocalins/urine , Proto-Oncogene Proteins/urine , Acute Kidney Injury/epidemiology , Incidence , Prospective Studies
20.
Article in Portuguese | LILACS | ID: lil-718810

ABSTRACT

A terapia antineoplásica tradicional apresenta algumas limitações que podem ser superadas através da utilização dos lipossomas. Estes nanossistemas de carreamento possibilitam o direcionamento de fármacos e reduzem efeitos secundários. Alguns peptídeos catiônicos sintetizados na pele de anuros apresentam atividade citotóxica seletiva (microorganismos e/ou tumores). Neste sentido, espécies do gênero Phyllomedusa secretam as dermaseptinas. Objetivou-se neste estudo, avaliar a citotoxicidade in vitro da dermaseptina 01 (DS 01) livre e encapsulada em lipossomas unilamelares pequenos (SUVs) em células tumorais humanas. Os lipossomas foram preparados pelo método de hidratação do filme lipídico seguido de sonicação. Foram produzidas formulações neutras e catiônicas, convencionais e furtivas. A citotoxicidade foi analisada em células tumorais de pulmão (NCI-H292), cólon (HT-29) e laringe (HEp-2), pelo ensaio de redução do sal tetrazólio (MTT) em placas de 96 poços. Os lipossomas foram submetidos a testes de estabilidade acelerada e em longo prazo. Em NCI-H292, a DS 01 livre apresentou efeito citostático médio de 35,6%. A encapsulação do peptídeo em lipossomas convencionais neutros aumentou o efeito, ao contrário dos furtivos. Para HT-29 e HEp-2, a DS 01 livre inibiu o crescimento celular em aproximadamente 50%, em média. A encapsulação em lipossomas catiônicos potencializou o efeito; os lipossomas convencionais inibiram na faixa de 80% e os furtivos, mais que 95% para as duas linhagens celulares. A DS 01, um peptídeo catiônico antimicrobiano, apresentou efeito citotóxico in vitro para células tumorais humanas que foi potencializado com a nanoencapsulação...


The conventional anticancer therapies show some limitations that can be overcome by using liposomes. This type of nanocarriers allows preferential targeting of drugs and reduces undesirable secondary effects. Some cationic peptides synthesized by the skin of anurans exhibit selective cytotoxicity (to pathogens and/or tumors). Species of Phyllomedusa secrete dermaseptins (DSs). The aim of this study was to assess the in vitro cytotoxicity of free and small unilamellar vesicle (SUV)-encapsulated dermaseptin 01 (DS 01) in various human tumor cells. Liposomes were prepared by lipid film hydration followed by sonication. Neutral and cationic, conventional and stealth liposomes were produced. Cytotoxicity was analyzed in lung (NCI-H292), colon (HT-29) and larynx (HEp-2) cancer cells, by the tetrazolium reduction method (MTT) carried out in 96-well microplates. Liposomes were tested for accelerated and long-term stability. In NCI-H292, free DS 01 showed a medium cytostatic effect of 36.5%. The conventional neutral liposome encapsulation of peptide increased this effect, whereas the stealth did not. In HT-29 and HEp-2, free DS 01 inhibited the cell growth by approximately 50% on average. The cationic liposome encapsulation was synergic, inhibition being about 80% in conventional and higher than 95% in stealth liposomes for both celllines. Thus, DS 01, an antimicrobial cationic peptide, showed in vitro cytotoxicity to human tumor cells that was potentiated by nanoencapsulation...


Subject(s)
Antineoplastic Agents/toxicity , In Vitro Techniques
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