RESUMO
Recently, there have been numerous cases of leishmaniasis reported in different Brazilian states. The use of furazolidone (FZD) to treat leishmaniasis has been previously described; however, the drug is associated with adverse effects such as anorexia, weight loss, incoordination, and fatigue in dogs. Thus, in the present study, we prepared and evaluated inclusion complexes between FZD and ß-cyclodextrin (ß-CD) to guarantee increased drug solubility and reduce the toxicity associated with high doses. The FZD:ß-CD complexes were prepared by two different techniques (kneading and lyophilization) prior to incorporation in an oral pharmaceutical dosage form. Formation of the complexes was confirmed using appropriate physicochemical methods. Antileishmanial activity against L. amazonensis was tested in vitro via a microplate assay using resazurin dye and cytotoxicity was determined using the fibroblast L929 lineage. Solubility studies showed the formation of complexes with complexation efficiencies lower than 100%. Physicochemical analysis revealed that FZD was inserted into the ß-CD cavity after complexation by both methods. Biological in vitro evaluations demonstrated that free FZD and the FZD:ß-CD complexes presented significant leishmanicidal activity against L. amazonensis with IC50 values of 6.16⯵g/mL and 1.83⯵g/mL for the complexes prepared by kneading and lyophilization, respectively. The data showed that these complexes reduced the survival of promastigotes and presented no toxicity for tested cells. Our results indicate that the new compounds could be a cost-effective alternative for use in the pharmacotherapy of leishmaniasis in dogs infected with L. amazonensis.
Assuntos
Antiprotozoários/farmacologia , Furazolidona/farmacologia , Leishmania mexicana/efeitos dos fármacos , beta-Ciclodextrinas/farmacologia , Animais , Antiprotozoários/efeitos adversos , Brasil , Furazolidona/efeitos adversos , Testes de Sensibilidade Parasitária , Resultado do Tratamento , beta-Ciclodextrinas/efeitos adversosRESUMO
Avaliou-se a eficiência de dois indutores da ovulação: cipionato de estradiol (CE) e benzoato de estradiol (BE), na inseminação artificial em tempo fixo (IATF). Foram utilizadas 128 novilhas. Todos os animais foram submetidos ao mesmo protocolo de sincronização, a partir do dia 8 os animais foram distribuídos em dois tratamentos: Tratamento com CE no dia 8 (64 novilhas) e tratamento com BE no dia 9 (64 novilhas). Quanto ao número de folículos, só observou-se diferença significativa entre os tratamentos no dia 8. Não houve diferença (p>0,05) para taxa de crescimento folicular, diâmetro do folículo dominante (10,97 ± 1,24 e 9,77 ± 1,36 mm), e intervalo da ovulação à inseminação artificial (13,20 ± 3,79 e 23,00 ± 14,28 horas) entre os tratamentos. A retirada do dispositivo de progesterona à ovulação, em horas, foi de 60,60±3,69 e 74,75±15,17 horas, respectivamente para CE e BE (p 0,05). Houve diferença (p 0,05) entre os tratamentos para a taxa de ovulação, que foi de 90,00% e 40,00% para CE e BE, respectivamente. A taxa de prenhez foi de 37,3% (p0,05) para ambos tratamentos. A administração de CE no dia 8 possibilitou a redução de um manejo na IATF em novilhas sem influenciar na taxa de prenhez.(AU)
We evaluated the efficiency of two ovulation induction: estradiol cypionate (EC) and estradiol benzoate (EB), at fixed time artificial insemination (TAI). 128 heifers were used. All animals were subjected to the same synchronization protocol, from the 8th day animals were divided into two treatments: Treatment with CE on the 8th (64 heifers) and treatment with EB on Day 9 (64 heifers). Regarding the number of follicles, only there was a significant difference between treatments at day 8. There was no difference (p> 0.05) for follicular growth rate, diameter of the dominant follicle (10.97 ± 1.24 and 9, 77 ± 1.36 mm) and range of ovulation in artificial insemination (13.20 ± 3.79 and 23.00 ± 14.28 hours) between treatments. The withdrawal of progesterone device ovulation in hours was 60.60 ± 3.69 and 74.75 ± 15,17 hours respectively for CE and BE (p <0.05). There were differences (p <0.05) between treatments for ovulation rate, which was 90.00% and 40.00% for CE and BE, respectively. The pregnancy rate was 37.3% (p 0.05) for both treatments. The EC administration on 81 Centro enabled the reduction of management in the TAI in heifers without influencing pregnancy rate.(AU)
Se evaluó la eficiencia de la inducción de la ovulación de dos: cipionato de estradiol (CE) y benzoato de estradiol (EB), en la inseminación artificial de tiempo fijo (TAI). Se utilizaron 128 novillas. Todos los animales fueron sometidos al mismo protocolo de sincronización, a partir de los animales se dividieron en dos tratamientos 8º: El tratamiento con CE en la octava (64 novillas) y el tratamiento con EB en el Día 9 (64 novillas). En cuanto al número de folículos, solamente había una diferencia significativa entre los tratamientos en el día 8. No hubo diferencia (p> 0,05) para la tasa de crecimiento folicular, el diámetro del folículo dominante (10,97 ± 1,24 y 9, 77 ± 1,36 mm) y el rango de la ovulación en la inseminación artificial (13,20 ± 3,79 y 23,00 ± 14,28 horas) entre tratamientos. La retirada del dispositivo de progesterona ovulación en horas fue 60,60 ± 3,69 y 74,75 ± 15,17 horas, respectivamente, para el CE y BE (p <0,05). Hubo diferencias (p <0,05) entre los tratamientos para la tasa de ovulación, que fue 90,00% y 40,00% para CE y ser, respectivamente. La tasa de embarazo fue de 37,3% (p 0,05) en ambos tratamientos. La administración CE el 8 de activar la reducción de la gestión en el TAI en novillas sin influir en la tasa de embarazo.(AU)
Assuntos
Animais , Feminino , Gravidez , Bovinos , Estradiol/uso terapêutico , Fenômenos Reprodutivos Fisiológicos , Inseminação Artificial/veterinária , Benzoatos , Taxa de GravidezRESUMO
Avaliou-se a eficiência de dois indutores da ovulação: cipionato de estradiol (CE) e benzoato de estradiol (BE), na inseminação artificial em tempo fixo (IATF). Foram utilizadas 128 novilhas. Todos os animais foram submetidos ao mesmo protocolo de sincronização, a partir do dia 8 os animais foram distribuídos em dois tratamentos: Tratamento com CE no dia 8 (64 novilhas) e tratamento com BE no dia 9 (64 novilhas). Quanto ao número de folículos, só observou-se diferença significativa entre os tratamentos no dia 8. Não houve diferença (p>0,05) para taxa de crescimento folicular, diâmetro do folículo dominante (10,97 ± 1,24 e 9,77 ± 1,36 mm), e intervalo da ovulação à inseminação artificial (13,20 ± 3,79 e 23,00 ± 14,28 horas) entre os tratamentos. A retirada do dispositivo de progesterona à ovulação, em horas, foi de 60,60±3,69 e 74,75±15,17 horas, respectivamente para CE e BE (p 0,05). Houve diferença (p 0,05) entre os tratamentos para a taxa de ovulação, que foi de 90,00% e 40,00% para CE e BE, respectivamente. A taxa de prenhez foi de 37,3% (p0,05) para ambos tratamentos. A administração de CE no dia 8 possibilitou a redução de um manejo na IATF em novilhas sem influenciar na taxa de prenhez.
We evaluated the efficiency of two ovulation induction: estradiol cypionate (EC) and estradiol benzoate (EB), at fixed time artificial insemination (TAI). 128 heifers were used. All animals were subjected to the same synchronization protocol, from the 8th day animals were divided into two treatments: Treatment with CE on the 8th (64 heifers) and treatment with EB on Day 9 (64 heifers). Regarding the number of follicles, only there was a significant difference between treatments at day 8. There was no difference (p> 0.05) for follicular growth rate, diameter of the dominant follicle (10.97 ± 1.24 and 9, 77 ± 1.36 mm) and range of ovulation in artificial insemination (13.20 ± 3.79 and 23.00 ± 14.28 hours) between treatments. The withdrawal of progesterone device ovulation in hours was 60.60 ± 3.69 and 74.75 ± 15,17 hours respectively for CE and BE (p <0.05). There were differences (p <0.05) between treatments for ovulation rate, which was 90.00% and 40.00% for CE and BE, respectively. The pregnancy rate was 37.3% (p 0.05) for both treatments. The EC administration on 81 Centro enabled the reduction of management in the TAI in heifers without influencing pregnancy rate.
Se evaluó la eficiencia de la inducción de la ovulación de dos: cipionato de estradiol (CE) y benzoato de estradiol (EB), en la inseminación artificial de tiempo fijo (TAI). Se utilizaron 128 novillas. Todos los animales fueron sometidos al mismo protocolo de sincronización, a partir de los animales se dividieron en dos tratamientos 8º: El tratamiento con CE en la octava (64 novillas) y el tratamiento con EB en el Día 9 (64 novillas). En cuanto al número de folículos, solamente había una diferencia significativa entre los tratamientos en el día 8. No hubo diferencia (p> 0,05) para la tasa de crecimiento folicular, el diámetro del folículo dominante (10,97 ± 1,24 y 9, 77 ± 1,36 mm) y el rango de la ovulación en la inseminación artificial (13,20 ± 3,79 y 23,00 ± 14,28 horas) entre tratamientos. La retirada del dispositivo de progesterona ovulación en horas fue 60,60 ± 3,69 y 74,75 ± 15,17 horas, respectivamente, para el CE y BE (p <0,05). Hubo diferencias (p <0,05) entre los tratamientos para la tasa de ovulación, que fue 90,00% y 40,00% para CE y ser, respectivamente. La tasa de embarazo fue de 37,3% (p 0,05) en ambos tratamientos. La administración CE el 8 de activar la reducción de la gestión en el TAI en novillas sin influir en la tasa de embarazo.