Resumo
Chemotherapy agents have some undesirable and non-selective cytostatic effects. Considering that kidneys are vulnerable to drug-induced toxicity, this study evaluated renal injury caused by vincristine sulfate (VS) in 12 female dogs diagnosed with transmissible venereal tumor (TVT). The animals were treated with VS (0.025 mg/kg IV) every 7 days for 4 weeks. During treatment, the animals were subjected to clinical examination, blood count, serum measurement of symmetric dimethylarginine (SDMA), blood urea nitrogen (BUN), creatinine, alanine aminotransferase, and alkaline phosphatase. In addition, urinalysis and urinary gamma-glutamyl transferase (GGT) measurements were performed. All parameters were determined three times: before beginning the treatment (T0), after 14 days (T1), and after 28 days (T2). During the study period, there were no changes in serum urea or creatinine levels, urine specific gravity, or persistent proteinuria. Furthermore, urinary GGT measurement did not indicate tubular lesions, and consistent elevation of SDMA was found in only one patient above the reference range. The results showed that weekly therapy with VS as a single agent for 28 days does not induce renal injury in most cases.(AU)
Os agentes quimioterápicos possuem efeitos citostáticos indesejáveis e não seletivos. Considerando a vulnerabilidade renal à toxicidade induzida por drogas, este estudo avaliou a lesão renal causada pelo sulfato de vincristina (VS) em 12 cadelas com diagnóstico de tumor venéreo transmissível (TVT). Os animais foram tratados com VS (0,025 mg / kg IV) a cada sete dias, durante quatro semanas. No transcurso do tratamento, os animais foram submetidos a exame clínico, hemograma, dosagem sérica de dimetilarginina simétrica (SDMA), nitrogênio ureico sanguíneo (BUN), creatinina, alanina aminotransferase e fosfatase alcalina. Além disso, foram realizadas análises de urina e medições de gama-glutamil transferase (GGT) urinária. Todos os parâmetros foram mensurados em três tempos, antes do início do tratamento (T0), aos 14 dias (T1) e aos 28 dias (T2). Durante o período do estudo, não houve alterações nas concentrações de ureia ou creatinina séricas, na gravidade específica da urina ou proteinúria persistente. Além disso, a medição de GGT urinária não indicou lesões tubulares, e elevação consistente de SDMA foi encontrada em apenas um paciente acima do intervalo de referência. Os resultados mostraram que a terapia semanal com VS como agente único por 28 dias não induz lesão renal na maioria dos casos.(AU)
Assuntos
Animais , Feminino , Cães , Tumores Venéreos Veterinários/tratamento farmacológico , Vincristina/efeitos adversos , Insuficiência Renal Crônica/veterinária , Exames Médicos , Cães/lesõesResumo
Este trabalho visou avaliar os efeitos de sulfato de vincristine sobre os testículos de ratos tratados na fase pré púbere, sobretudo quanto às alterações das células de Sertoli e das células germinativas. Foram utilizados 30 animais controles e 30 tratados com sulfato de vincristine. As aplicações da droga ocorreram aos 15 dias de vida, e a eutanásia aos 40, 64 e 127 dias de vida para possibilitar a avaliação em diferentes estágios de desenvolvimento reprodutivo. Foram realizadas medidas biométricas (pesos corpóreos e testiculares), medidas morfométricas testiculares, (eixos testiculares maiores e menores, diâmetros testiculares de túbulo e lúmen seminíferos, e altura do epitélio seminífero) e estereológicas (volumes testiculares e as densidades de volume do tecido tubular e do tecido intersticial testicular). As medidas biométricas foram feitas em todos os animais do experimento, e as avaliações morfométricas e estereológicas foram realizadas em 200 túbulos seminíferos. Os resultados demonstraram que sulfato de vincristine reduz parâmetros biométricos como peso corpóreo, peso testicular e volume testicular total. Variáveis morfométricas e estereológicas como diâmetro dos túbulos seminíferos, altura do epitélio seminífero e volume dos túbulos seminíferos também foram reduzidos. Os tipos celulares mais atingidos foram as espermatogônias, espermátides tardias e células de Sertoli.(AU)
This study evaluated the vincristine sulfate effect on rat testes treated in pre pubertal stage, especially regarding the changes of Sertoli cells and germ cells. Thirty control rats and 30 rats treated with vincristine sulfate were used. The drug application occurred at 15 days of life, and euthanasia at 40, 64 and 127 days of life to enable evaluation at different stages of reproductive development. Biometric measurements were performed (body and testicular weights), testicular morphometric measures (major and minor testicular axis and of seminiferous tubule and seminiferous lumen) and stereological (testicular volumes and volume densities of the tubular and testicular interstitial tissue). The biometric measurements were made on all rats in the experiment, and morphometric and stereological analysis was carried out in 200 seminiferous tubules. The results demonstrate that vincristine sulfate reduces biometric parameters such as body weight, testicular weight and the total testicular volume. Morphometric and stereological variables as diameter of the seminiferous tubules, height of the seminiferous epithelium and volume of the seminiferous tubules were also reduced. The most affected cell types were spermatogonia, late spermatids and Sertoli cells.(AU)
Assuntos
Animais , Ratos , Ratos Endogâmicos/anormalidades , Vincristina/efeitos adversos , Testículo/anormalidadesResumo
Este trabalho visou avaliar os efeitos de sulfato de vincristine sobre os testículos de ratos tratados na fase pré púbere, sobretudo quanto às alterações das células de Sertoli e das células germinativas. Foram utilizados 30 animais controles e 30 tratados com sulfato de vincristine. As aplicações da droga ocorreram aos 15 dias de vida, e a eutanásia aos 40, 64 e 127 dias de vida para possibilitar a avaliação em diferentes estágios de desenvolvimento reprodutivo. Foram realizadas medidas biométricas (pesos corpóreos e testiculares), medidas morfométricas testiculares, (eixos testiculares maiores e menores, diâmetros testiculares de túbulo e lúmen seminíferos, e altura do epitélio seminífero) e estereológicas (volumes testiculares e as densidades de volume do tecido tubular e do tecido intersticial testicular). As medidas biométricas foram feitas em todos os animais do experimento, e as avaliações morfométricas e estereológicas foram realizadas em 200 túbulos seminíferos. Os resultados demonstraram que sulfato de vincristine reduz parâmetros biométricos como peso corpóreo, peso testicular e volume testicular total. Variáveis morfométricas e estereológicas como diâmetro dos túbulos seminíferos, altura do epitélio seminífero e volume dos túbulos seminíferos também foram reduzidos. Os tipos celulares mais atingidos foram as espermatogônias, espermátides tardias e células de Sertoli.(AU)
This study evaluated the vincristine sulfate effect on rat testes treated in pre pubertal stage, especially regarding the changes of Sertoli cells and germ cells. Thirty control rats and 30 rats treated with vincristine sulfate were used. The drug application occurred at 15 days of life, and euthanasia at 40, 64 and 127 days of life to enable evaluation at different stages of reproductive development. Biometric measurements were performed (body and testicular weights), testicular morphometric measures (major and minor testicular axis and of seminiferous tubule and seminiferous lumen) and stereological (testicular volumes and volume densities of the tubular and testicular interstitial tissue). The biometric measurements were made on all rats in the experiment, and morphometric and stereological analysis was carried out in 200 seminiferous tubules. The results demonstrate that vincristine sulfate reduces biometric parameters such as body weight, testicular weight and the total testicular volume. Morphometric and stereological variables as diameter of the seminiferous tubules, height of the seminiferous epithelium and volume of the seminiferous tubules were also reduced. The most affected cell types were spermatogonia, late spermatids and Sertoli cells.(AU)
Assuntos
Animais , Ratos , Ratos Endogâmicos/anormalidades , Vincristina/efeitos adversos , Testículo/anormalidadesResumo
Purpose: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Methods: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. Results: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. Conclusion: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.(AU)
Assuntos
Animais , Masculino , Camundongos , Interleucina-4/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Vincristina/efeitos adversos , Modelos AnimaisResumo
PURPOSE:To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment.METHODS:Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated.RESULTS:Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (p<0.05) between 6 hours and 24 hours, 6 hours and 18 hours through visual observation. However, the inflammation happened 6 hours after infusion, the loss of venous endothelial cells demonstrated differences among four groups through histopathological evaluation (p<0.05). There were significant differences (p<0.05) after 4 days among the intervention groups through visual observation, the effects of Xianchen group (five times a day) were better than Xianchen group (tid) (p<0.01). The treatment of edema demonstrated differences among groups through histopathological evaluation (p<0.05), Xianchen (five times a day) better relieved the degree of edema (p<0.05).CONCLUSIONS:The study showed that inflammatory reaction of phlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.(AU)
Assuntos
Animais , Coelhos , Flebite/tratamento farmacológico , Flebite/veterinária , Vincristina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/toxicidade , Medicamentos de Ervas Chinesas/uso terapêuticoResumo
Background: Peripheral neuropathies secondary to chemotherapy drugs, especially when it comes to the use of vincristine, are common in humans, but rare in dogs. Neurologic manifestation depends on the kind of axonal fibers involved. When motor fibers are affected, weakness and ataxia are observed. Sensory fibers involvement, which can lead to hyperesthesia, hypoesthesia or paresthesia was reported experimentally in rats, and is common in humans but were never reported in dogs. Thus, this report aims at describing a mixed neuropathy, with sensory and motor involvement, in a dog after vincristine treatment. Case: A one year old mixed breed dog, rescued from the street, was presented with multiple nodular and ulcerated lesions, disseminated on the head, gums, flank and limbs, with progressive worsening in the last two months. Cytology of two subcutaneous and one gum nodule revealed an intense concentration of neutrophils and round cells with abnormally clumped chromatin patterns, prominent nucleoli and multiple cytoplasmic vacuoles, compatible with TVT. Treatment was initiated with a weekly administration of vincristine (0,75 mg/m2 ) combined with anti-emetic (maropitant) and H1 receptor inhibitor (ranitidine). Fast remission of the cutaneous lesions occurred. However, after the second chemo session, generalized hyperesthesia, mild ataxia, intermittent collapse and vomiting were...(AU)
Assuntos
Animais , Cães , Transtornos das Habilidades Motoras/induzido quimicamente , Doenças do Sistema Nervoso Periférico/veterinária , Vincristina/efeitos adversos , Preparações Farmacêuticas/administração & dosagemResumo
Background: Peripheral neuropathies secondary to chemotherapy drugs, especially when it comes to the use of vincristine, are common in humans, but rare in dogs. Neurologic manifestation depends on the kind of axonal fibers involved. When motor fibers are affected, weakness and ataxia are observed. Sensory fibers involvement, which can lead to hyperesthesia, hypoesthesia or paresthesia was reported experimentally in rats, and is common in humans but were never reported in dogs. Thus, this report aims at describing a mixed neuropathy, with sensory and motor involvement, in a dog after vincristine treatment. Case: A one year old mixed breed dog, rescued from the street, was presented with multiple nodular and ulcerated lesions, disseminated on the head, gums, flank and limbs, with progressive worsening in the last two months. Cytology of two subcutaneous and one gum nodule revealed an intense concentration of neutrophils and round cells with abnormally clumped chromatin patterns, prominent nucleoli and multiple cytoplasmic vacuoles, compatible with TVT. Treatment was initiated with a weekly administration of vincristine (0,75 mg/m2 ) combined with anti-emetic (maropitant) and H1 receptor inhibitor (ranitidine). Fast remission of the cutaneous lesions occurred. However, after the second chemo session, generalized hyperesthesia, mild ataxia, intermittent collapse and vomiting were...