Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 65
Filter
1.
Journal of Integrative Medicine ; (12): 451-459, 2021.
Article in English | WPRIM | ID: wpr-888770

ABSTRACT

OBJECTIVE@#Chemotherapeutic drugs, such as cisplatin (CP), which are associated with oxidative stress and apoptosis, may adversely affect the reproductive system. This study tests whether administration of propolis and nano-propolis (NP) can alleviate oxidative stress and apoptosis in rats with testicular damage induced by CP.@*METHODS@#In this study, polymeric nanoparticles including propolis were synthesized with a green sonication method and characterized using Fourier transform-infrared spectroscopy, Brunauer-Emmett-Teller, and wet scanning transmission electron microscopy techniques. In total, 56 rats were divided into the following seven groups: control, CP, propolis, NP-10, CP + propolis, CP + NP-10, and CP + NP-30. Propolis (100 mg/kg), NP-10 (10 mg/kg), and NP-30 (30 mg/kg) treatments were administered by gavage daily for 21 d, and CP (3 mg/kg) was administered intraperitoneally in a single dose. After the experiment, oxidative stress parameters, namely, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT), and apoptotic pathways including B cell leukemia/lymphoma-2 protein (Bcl-2) and Bcl-2-associated X protein (Bax) were measured in testicular tissues. Furthermore, sperm quality and weights of the testis, epididymis, right cauda epididymis, seminal vesicles and prostate were evaluated.@*RESULTS@#Propolis and NP (especially NP-30) were able to preserve oxidative balance (decreased MDA levels and increased GSH, CAT, and GPx activities) and activate apoptotic pathways (decreased Bax and increased Bcl-2) in the testes of CP-treated rats. Sperm motility in the control, CP, and CP + NP-30 groups were 60%, 48.75%, and 78%, respectively (P < 0.001). Especially, NP-30 application completely corrected the deterioration in sperm features induced by CP.@*CONCLUSION@#The results show that propolis and NP treatments mitigated the side effects of CP on spermatogenic activity, antioxidant situation, and apoptosis in rats.


Subject(s)
Animals , Antioxidants/metabolism , Cisplatin/toxicity , Male , Oxidative Stress , Propolis , Rats , Rats, Sprague-Dawley , Sperm Motility , Testis
2.
Braz. j. otorhinolaryngol. (Impr.) ; 86(2): 222-227, March-Apr. 2020. graf
Article in English | LILACS | ID: biblio-1132576

ABSTRACT

Abstract Introduction: The use of electron microscopy in the study of the inner ear has allowed us to observe minute details of the hair cells, especially in ototoxicity studies; however, the preparation of this material is a difficult and delicate task. In an attempt to simplify the handling of these materials, two agents, toluidine blue and ethylenediamine tetra-acetic acid were tested, in addition to the elimination of osmium tetroxide during the preparation of albino guinea pig cochleae. We also tested the applicability of these methodologies in an ototoxicity protocol. Objective: To verify the quality of the images obtained with and without the use of ethylenediamine tetra-acetic acid, toluidine blue and osmium tetroxide in the preparation of cochleae of albino guinea pigs for the scanning electron microscopy. Methods: Three groups of cochleae were used. In Group 1, 10 cochleae were prepared with the usual methodology, dissecting the optical capsule without decalcification and using osmium tetroxide as a post-fixative agent. In Group 2, we prepared 10 cochleae decalcified with ethylenediamine tetra-acetic acid, injecting toluidine blue in the endolymphatic space to facilitate the identification of the organ of Corti. In Group 3, we used 4 cochleae of guinea pigs that received 3 doses of cisplatin (7.5 mg/kg, D1-D5-D6), two prepared according to the methodology used in Group 1 and two with that used in Group 2. Scanning electron microscopy images were obtained from the organ of Corti region of the basal turn of each cochlea. Results: The organ of Corti was more easily identified with the use of toluidine blue. The dissection of the cochlea was more accurate in the decalcified cochleae. The quality of the images and the preservation of the organ of Corti obtained with the two methodologies were similar. Conclusion: The proposed modifications resulted in images of similar quality as those observed using the traditional methodology.


Resumo Introdução: O emprego da microscopia eletrônica no estudo da orelha interna permitiu observar detalhes minuciosos das células ciliadas especialmente em estudos de ototoxicidade. Entretanto, o preparo desse material é trabalhoso e delicado. Para simplificar a manipulação desses materiais, testou-se o uso de dois agentes, azul de toluidina e ácido etilenodiamino tetra-acético, além da retirada do tetróxido de ósmio na preparação de cócleas de cobaias albinas. Testamos também a aplicabilidade dessas metodologias em um protocolo de ototoxicidade. Objetivo: Verificar a qualidade das imagens obtidas com e sem o uso de ácido etilenodiamino tetra-acético, azul de toluidina e tetróxido de ósmio na preparação de cócleas de cobaias albinas para a microscopia eletrônica de varredura. Método: Foram utilizados três grupos de cócleas. No Grupo 1 preparou-se 10 cócleas com a metodologia usual, dissecando a cápsula ótica sem descalcificac¸ão e utilizando tetróxido de ósmio como pós-fixador. No Grupo 2 preparamos 10 cócleas descalcificadas com ácido etilenodiamino tetra-acético, injetando azul de toluidina no espac¸o endolinfático para facilitar a identificação do órgão de Corti. No Grupo 3 utilizamos 4 cócleas de cobaias que receberam 3 doses de cisplatina (7,5 mg/kg, D1-D5-D6), duas preparadas com a metodologia do Grupo 1 e duas com a do Grupo 2. Foram obtidas imagens da microscopia eletrônica de varredura da região do órgão de Corti do giro basal de cada cóclea. Resultados: O órgão de Corti foi mais facilmente identificado com o azul de touidina. A dissecção da cóclea foi mais precisa nas cócleas descalcificadas A qualidade das imagens e a preservac¸ão do órgão de Corti obtidas com as duas metodologias foi similar. Conclusão: As modificações propostas resultaram em imagens de qualidade similar as observadas com o uso da metodologia tradicional.


Subject(s)
Animals , Female , Cisplatin/toxicity , Cochlea/drug effects , Cochlea/ultrastructure , Organ of Corti/drug effects , Organ of Corti/ultrastructure , Osmium Tetroxide/administration & dosage , Tolonium Chloride/administration & dosage , Microscopy, Electron, Scanning , Edetic Acid/administration & dosage , Guinea Pigs , Hair Cells, Auditory/drug effects , Hair Cells, Auditory/ultrastructure
3.
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
4.
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
5.
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
6.
Braz. j. otorhinolaryngol. (Impr.) ; 85(3): 267-274, May-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1011617

ABSTRACT

Abstract Introduction: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. Objective: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Methods: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15 mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days. Cisplatin + gallic acid group received intraperitoneal gallic acid at 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day. A control group received 1 mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. Results: In cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the cisplatin + gallic acid group, this biochemical, histopathological and functional changes were reversed. Conclusion: In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic emissions test results, biochemical findings and immunohistochemical analyses.


Resumo Introdução: A cisplatina é um agente antineoplásico amplamente usado no tratamento de vários tipos de câncer. A ototoxicidade é um dos principais efeitos colaterais que restringem o uso da cisplatina. Objetivo: O objetivo deste estudo foi investigar a eficácia protetora do ácido gálico, em termos bioquímicos, funcionais e histopatológicos, contra a ototoxicidade induzida por cisplatina. Método: Vinte e oito ratas Sprague-Dawley foram incluídas. As ratas foram distribuídas aleatoriamente em quatro grupos de sete animais cada. O grupo cisplatina recebeu uma única dose intraperitoneal de 15 mg/kg de cisplatina. O grupo ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos. O grupo cisplatina + ácido gálico recebeu ácido gálico via intraperitoneal a uma dose de 100 mg/kg durante cinco dias consecutivos e uma única dose intraperitoneal de 15 mg/kg de cisplatina no terceiro dia. O grupo controle recebeu 1 mL de solução salina via intraperitoneal por cinco dias consecutivos. Antes da administração do fármaco, todos os ratos foram expostos ao teste de emissões otoacústicas - produto de distorção. O teste foi repetido no sexto dia do estudo. Todos os ratos foram então sacrificados; as cócleas foram removidas e reservadas para análises bioquímicas e histopatológicas. Resultados: No grupo cisplatina, os valores da relação sinal-ruído do dia 6 foram significativamente mais baixos aos dos outros grupos. Além disso, os níveis de malondialdeído nos tecidos cocleares foram significativamente mais altos, e as atividades de superóxido dismutase e glutatione peroxidase foram significativamente mais baixas em comparação com o grupo controle. A avaliação histopatológica revelou erosão na estria vascular, degeneração e edema na camada de tecido conjuntivo em células endoteliais, comprometimento das células ciliadas externas e diminuição do número dessas células. No grupo cisplatina + ácido gálico, estas alterações bioquímicas, histopatológicas e funcionais foram revertidas. Conclusão: Tendo em vista os nossos achados, consideramos que o ácido gálico pode ter desempenhado um papel protetor contra a ototoxicidade induzida por cisplatina em ratas, conforme indicado pelos resultados do teste emissões otoacústicas - produto de distorção, achados bioquímicos e análises imuno-histoquímicas.


Subject(s)
Animals , Female , Rats , Cisplatin/toxicity , Otoacoustic Emissions, Spontaneous/drug effects , Cochlea/drug effects , Cochlea/pathology , Protective Agents/administration & dosage , Gallic Acid/administration & dosage , Acoustic Stimulation , Immunohistochemistry , Rats, Sprague-Dawley , Disease Models, Animal , Injections, Intraperitoneal
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.
Bol. méd. postgrado ; 34(2): 12-16, Jul-Dic. 2018. tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1120810

ABSTRACT

Con el objetivo de determinar los efectos ototóxicos del cisplatino y su relación con la aparición de hipoacusia en pacientes con cáncer de cuello uterino que asistieron al Servicio Autónomo de Oncología del estado Lara durante el lapso octubre 2017-febrero 2018, se realizó un estudio descriptivo transversal en 16 pacientes siendo las más afectadas el grupo de edad entre 36-45 años (43,2%). Los síntomas auditivos antes de iniciar el tratamiento fueron pérdida de la audición (6,2%); después del primero y segundo ciclo de quimioterapia se reportaron acúfenos (62,5% y 68,7%, respectivamente) siendo en la mayoría del tipo agudo (60% y 81,8% respectivamente) y pérdida de la audición (37,5% y 31,2% respectivamente). Los valores audiométricos al inicio fueron hipoacusia superficial para 25db (31,2%) y 30db (25%) en cambio, después del primero y segundo ciclo, fue hipoacusia superficial de tipo neurosensorial a predominio de frecuencias agudas con valores de 35db (31,2%) y de 40db (31,2%), respectivamente. Los hallazgos audiométricos mostraron que 56,2% de las pacientes presentaban hipoacusia superficial al inicio; pero luego se reportó 50% de pacientes con hipoacusia superficial de tipo neurosensorial a predominio de frecuencias agudas, posterior a ambos ciclos. Los resultados obtenidos permiten identificar de forma temprana las pacientes susceptibles de desarrollar hipoacusia posterior al tratamiento adyuvante con cisplatino(AU)


With the objective of determining the ototoxic effects of cisplatin and its relationship with the onset of hearing loss in patients with cervical cancer who attended the Autonomous Oncology Service of Lara state, during the period October 2017-February 2018; A cross-sectional descriptive study was conducted, obtaining 16 patients, being the most affected the age group between 36-45 years (43.25%), and the ranges of 25-35 years and 46-55 years (25%, respectively) . Hearing symptoms before starting treatment were hearing loss (6.25%); After the first and second cycle, tinnitus was reported (62.5% and 68.75%), being most of the acute type (60% and 81.81%) and hearing loss (37.5% and 31%). 25%). The audiometric values at the beginning were superficial hypoacusis for 25db (31.25%) and 30db (25%); however, after the first and second cycle was hearing loss Surface-type neurosensory with a curve suggestive of grade I acoustic trauma with values of 35db (31.25%) and 40db (31.25%), respectively. The audiometric findings showed that 56.25% had superficial hearing loss at baseline; but, then, 50% were reported with superficial sensorineural hearing loss with a curve suggestive of grade I acoustic trauma, after both cycles. The results obtained allow the early identification of patients susceptible to developing hearing loss after adjuvant treatment with cisplatin(AU)


Subject(s)
Humans , Female , Adult , Uterine Cervical Neoplasms/physiopathology , Cisplatin/toxicity , Ototoxicity , Hearing Loss , Tinnitus/etiology , Ear, Inner/drug effects , Medical Oncology
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.
Int. j. morphol ; 34(2): 713-718, June 2016. ilus
Article in English | LILACS | ID: lil-787059

ABSTRACT

Cisplatin (EBEWE Pharma, Unterach, Austria) is an anti-cancer drug used in chemotherapy. One of the limiting major side effects of cisplatin is nephrotoxicity. Tribulus terrestris (TT) has been used as an synthetic or herbal protective agents for kidney disorders. The present study amid to investigate the Tribulus terrestris Hydroalcoholic extract effect on cisplatin-induced apoptosis in mice kidney. Male adult mice (n= 30) were divided into control group and 4 experimental groups (n= 6). Control group received saline, the first experimental group received cisplatin (5.5 mg/kg) and other three experimental groups received cisplatin (5.5 mg/kg) and different doses of hydroalcoholic extact of TT (100, 300 and 500 mg/kg i.p) respectively. The kidneys were removed after 4 days of injections, and TUNEL assay on mice's kidneys were performed. Weights of body and kidneys and apoptotic index were assessed. Data analysis was performed using one-way ANOVA followed by Tukey's post hoc test. The results showed that cisplatin lead to a reduction in the weight of body and kidney (P <0.01), and increased apoptotic index significantly compared to the control group (P <0.001), while in treated groups with TT, the weights of body and kidney were significantly higher compared with cisplatin group, but apoptotic index did not show significant differences. These parameters reached normal range after administration of fruit extracts of TT for 4 days. The study demonstrates that extract of TT could have protective effect on cisplatin- induced apoptosis of kidney. This may be related to the presence of antioxidant components acting via a multitude of central and peripheral mechanisms.


El cisplatino (EBEWE Pharma, Unterach, Austria) es un medicamento contra el cáncer utilizado en quimioterapia. Uno de los principales efectos secundarios limitantes del cisplatino es la nefrotoxicidad. Tribulus terrestris (TT) ha sido utilizado como agente protector sintético o herbal para los trastornos renales. El objetivo fue investigar el efecto del extracto hidroalcohólico de TT sobre la apoptosis inducida por cisplatino en el riñón de ratones. Se utilizaron ratones adultos machos (n= 30), que fueron divididos en 4 grupos, un control y tres grupos experimentales (n= 6). El grupo control recibió solución salina; el primer grupo experimental recibió cisplatino (5,5 mg/kg) y los otros tres grupos experimentales recibieron cisplatino (5,5 mg/kg) con diferentes dosis de extracto hidroalcohólico de TT (100, 300 y 500 mg/kg vía ip) respectivamente. Los riñones fueron retirados después de 4 días de aplicadas las inyecciones, y se realizó el ensayo TUNEL en los riñones. Se evaluó el peso corporal de los ratones, el peso de los riñones y el índice de apoptosis. El análisis de datos se realizó mediante ANOVA de un factor seguido por la prueba post hoc de Tukey. Los resultados mostraron que el cisplatino con plomo provocó una reducción en el peso corporal y el riñón (P <0,01) y un aumento significativo del índice de apoptosis en comparación con el grupo control (P <0,001), mientras que en los grupos tratados con TT, los pesos corporales y de los riñones fueron significativamente mayores en comparación con el grupo de cisplatino, pero el índice de apoptosis no mostró diferencias significativas. Estos parámetros alcanzaron niveles normales después de la administración de extracto de TT durante 4 días. El estudio demuestra que el extracto de TT podría tener un efecto protector sobre la apoptosis inducida por cisplatino en el riñón, que podría estar relacionado con la presencia de componentes antioxidantes que actúan a través de múltiples mecanismos centrales y periféricos.


Subject(s)
Animals , Male , Mice , Apoptosis/drug effects , Kidney/drug effects , Plant Extracts/administration & dosage , Tribulus , Analysis of Variance , Cisplatin/toxicity , Hydroalcoholic Solution , In Situ Nick-End Labeling , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Mice, Inbred BALB C
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.
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
14.
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
15.
Article in English | WPRIM | ID: wpr-42471

ABSTRACT

Bucillamine is used for the treatment of rheumatoid arthritis. This study investigated the protective effects of bucillamine against cisplatin-induced damage in auditory cells, the organ of Corti from postnatal rats (P2) and adult Balb/C mice. Cisplatin increases the catalytic activity of caspase-3 and caspase-8 proteases and the production of free radicals, which were significantly suppressed by pretreatment with bucillamine. Bucillamine induces the intranuclear translocation of Nrf2 and thereby increases the expression of gamma-glutamylcysteine synthetase (gamma-GCS) and glutathione synthetase (GSS), which further induces intracellular antioxidant glutathione (GSH), heme oxygenase 1 (HO-1) and superoxide dismutase 2 (SOD2). However, knockdown studies of HO-1 and SOD2 suggest that the protective effect of bucillamine against cisplatin is independent of the enzymatic activity of HO-1 and SOD. Furthermore, pretreatment with bucillamine protects sensory hair cells on organ of Corti explants from cisplatin-induced cytotoxicity concomitantly with inhibition of caspase-3 activation. The auditory-brainstem-evoked response of cisplatin-injected mice shows marked increases in hearing threshold shifts, which was markedly suppressed by pretreatment with bucillamine in vivo. Taken together, bucillamine protects sensory hair cells from cisplatin through a scavenging effect on itself, as well as the induction of intracellular GSH.


Subject(s)
Animals , Antioxidants/metabolism , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 8/metabolism , Cell Line , Cisplatin/toxicity , Cysteine/analogs & derivatives , Gene Expression Regulation/drug effects , Gene Knockdown Techniques , Glutathione/metabolism , Heme Oxygenase-1/genetics , Intracellular Space/metabolism , Male , Metabolic Detoxication, Phase II/genetics , Mice , NF-E2-Related Factor 2/genetics , Nitric Oxide/biosynthesis , Organ of Corti/drug effects , RNA Interference , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/genetics
16.
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
17.
Article in English | IMSEAR | ID: sea-162043

ABSTRACT

Objective: Mesenchymal stem cells (MSCs) have generated a great deal of excitement and promise as a potential source of cells for cell-based therapeutic strategies. These data provide the clue of using MSCs in the current work in correcting cisplatin-induced nephrotoxicity, the severest adverse effect of the well-known anticancer drug; cisplatin. Methods: MSCs of bone marrow origin of femora and tibiae of adult albino rats were separated, grown, propagated in culture then identified by both morphology and CD29 surface marker detection. MSCs were injected into the rats’’ tail veins one day after a single dose (5 mg/kg body weight) of intraperitoneal injection of cisplatin. Four weeks later kidney tissue was examined histopathologically and ultra-structurally. Renal functions s(urea, creatinine) as well as serum electrolytes levels (Na, K) were estimated Results: Cisplatin group demonstrated atrophied glomeruli, thickened glomerular basement membrane, dilated urinary space, loss of proximal convoluted tubules brush borders, loss of podocyte pedicels and collagen deposition. Tubular cells showed vacuolization and nuclear membrane degeneration. Serum levels of urea, creatinine, Na and K were significantly elevated. MSCs ameliorated cisplatin-induced nephrotoxicity to a great extent as evidenced histologically, ultra-structurally and biochemically. Conclusion: MSCs have a potential therapeutic effect against cisplatin induced nephrotoxicity.


Subject(s)
Adult , Animals , Cisplatin/toxicity , Kidney/chemistry , Kidney/drug effects , Kidney/toxicity , Kidney/ultrastructure , Male , Mesenchymal Stem Cell Transplantation/methods , Models, Animal , Rats , Rats, Sprague-Dawley
18.
Int. j. morphol ; 32(2): 551-557, jun. 2014. ilus
Article in English | LILACS | ID: lil-714308

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 has been used as an aphrodisiac. The present study amid to investigate protective effect of Tribulus terrestris hydroalcoholic extract against cisplatin-induced cytotoxicity on sperm parameters 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 groups received cisplatin (5.5 mg/kg) and different doses of hydroalcoholic extact of Tribulus terrestris (100, 300 and 500 mg/kg/i.p) respectively. On the day after the last injection, blood samples were collected for serum Nitric oxide (NO) assay. Also weights of body and testis, sperm parameters and seminiferous tubules diameter 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, sperm parameters and increased level serum of NO significantly compared to the control group (P<0.05), while in treated groups with Tribulus terrestris, the weights of body and testes, sperm parameters, seminiferous tubules diameter were significantly higher compared with cisplatin group (P<0.05), but serum level of NO did not show significant differences. The study demonstrates that extract of Tribulus terrestris could protective effect against cisplatin- induced cytotoxicity on sperm parameters that may be related to the presence of antioxidant components acting via a multitude of central and peripheral mechanisms.


El cisplatino es un medicamento contra el cáncer utilizado en la quimioterapia. Uno de los efectos secundarios limitantes de cisplatino es la decreciente función glándular genital, azoospermia y oligospermia. Tribulus terrestris ha sido utilizado como un afrodisíaco. En el presente estudio se investiga el efecto protector del extracto hidroalcohólico de Tribulus terrestris (TT) contra la citotoxicidad inducida por cisplatino en los parámetros espermáticos en ratones. Ratones adultos machos (n = 30) fueron divididos en 4 grupos control y experimentales (n = 6). En el grupo control se administró solución salina, el primer grupo experimental recibió cisplatino (5,5 mg/kg) mientras que otros tres grupos experimentales recibieron cisplatino (5.5 mg/kg) además de diferentes dosis de extracto hidroalcohólico de TT (100, 300 y 500 mg/kg/IP) respectivamente. El día siguiente de la última inyección, se analizaron muestras de sangre para expresión de óxido nítrito (ON). Además, fueron evaluados el peso del cuerpo y testículos, los parámetros espermáticos y el diámetro de los túbulos seminíferos. Los datos fueron analizados mediante análisis ANOVA y la prueba de Tukey. El uso de cisplatino causó reducción del peso corporal y testicular, parámetros espermáticos y aumento significativo de los valores de ON en comparación con el grupo control (P<0,05), mientras que los grupos tratados con TT, fue significativamente mayor el peso corporal y testicular, parámetros espermáticos y diámetro de los túbulos seminíferos en comparación al grupo tratado con cisplatino (P<0,05). No se observaron diferencias significativas en los valores ON. El extracto de TT puede tener un efecto protector frente a la citotoxicidad inducida por el cisplatino sobre los parámetros espermáticos, al estar relacionado a la presencia de componentes antioxidantes que actúan mediante mecanismos centrales y periféricos.


Subject(s)
Animals , Mice , Spermatozoa/drug effects , Plant Extracts/pharmacology , Tribulus/chemistry , Cisplatin/toxicity , Alcohols/chemistry , Mice, Inbred BALB C
19.
Article in Korean | WPRIM | ID: wpr-150516

ABSTRACT

PURPOSE: The purpose of this study was to examine the effects of Cu/Zn SOD on reduction of hindlimb muscular atrophy induced by cisplatin in rats. METHODS: Forty-two rats were assigned to three groups; control group, Cisplatin (CDDP) group and cisplatin with Cu/Zn SOD (CDDP-SOD) group. At day 35 hindlimb muscles were dissected. Food intake, activity, withdrawal threshold, muscle weight, and Type I, II fiber cross-sectional area (CSA) of dissected muscles were measured. Relative SOD activity and expression of MHC and phosphorylated Akt, ERK were measured after dissection. RESULTS: Muscle weight and Type I, II fiber CSA of hindlimb muscles in the CDDP group were significantly less than the control group. Muscle weight and Type I, II fiber CSA of hindlimb muscles, food intake, activity, and withdrawal thresholds of the CDDP-SOD group were significantly greater than the CDDP group. There were no significant differences in relative SOD activities of hindlimb muscles between the CDDP-SOD and CDDP groups. MHC expression and phosphorylated Akt, ERK of hindlimb muscles in the CDDP-SOD group were significantly greater than the CDDP group. CONCLUSION: Cu/Zn SOD attenuates hindlimb muscular atrophy induced by cisplatin through increased food intake and activity. Increment of phosphorylated Akt, ERK may relate to attenuation of hindlimb muscular atrophy.


Subject(s)
Animals , Body Weight/drug effects , Cisplatin/toxicity , Disease Models, Animal , Extracellular Signal-Regulated MAP Kinases/metabolism , Hindlimb , Male , Muscle, Skeletal/drug effects , Muscular Atrophy/chemically induced , Phosphorylation , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Recombinant Proteins/biosynthesis , Superoxide Dismutase/genetics , Superoxides/metabolism
20.
Article in English | WPRIM | ID: wpr-202217

ABSTRACT

OBJECTIVE: To investigate whether granulocyte-colony stimulating factor (G-CSF) can decrease the extent of ovarian follicle loss caused by cisplatin treatment. METHODS: Twenty-one adult female Sprague-Dawley rats were used. Fourteen rats were administered 2 mg/kg/day cisplatin by intraperitoneal injection twice per week for five weeks (total of 20 mg/kg). Half of the rats (n=7) were treated with 1 mL/kg/day physiological saline, and the other half (n=7) were treated with 100 microg/kg/day G-CSF. The remaining rats (n=7, control group) received no therapy. The animals were then euthanized, and both ovaries were obtained from all animals, fixed in 10% formalin, and stored at 4degrees C for paraffin sectioning. Blood samples were collected by cardiac puncture and stored at -30degrees C for hormone assays. RESULTS: All follicle counts (primordial, primary, secondary, and tertiary) and serum anti-Mullerian hormone levels were significantly increased in the cisplatin+G-CSF group compared to the cisplatin+physiological saline group. CONCLUSION: G-CSF was beneficial in decreasing the severity of follicle loss in an experimental rat model of cisplatin chemotherapy.


Subject(s)
Animals , Anti-Mullerian Hormone/blood , Antineoplastic Agents/toxicity , Biomarkers/blood , Cisplatin/toxicity , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Female , Fertility Preservation/methods , Granulocyte Colony-Stimulating Factor/therapeutic use , Ovarian Follicle/drug effects , Primary Ovarian Insufficiency/blood , Rats, Sprague-Dawley
SELECTION OF CITATIONS
SEARCH DETAIL