Avaliação do ciclo estral e da toxicidade sistêmica do látex de Himatanthus sucuuba (Spruce) Woodson em ratas Wistar / The estrous cycle evaluation and systemic toxicity in the latex of Himatanthus sucuuba (Spruce) Woodson in Wistar rats

It aimed to investigate the possible effects induced by the diluted latex oral administration of H. sucuuba(LdHs) in Wistar rats on the estrous cycle and other organ systems. The Wistar rats received by gavage the LdHs.The results showed that there was a decrease in average daily intake and ponderable development negativeinterference in the group treated with the dose 100 mg / kg. The number of primary follicles and in the dose 100 mg/ kg LdHs was superior to the control group. It was also observed a decrease in the number of estrous cycles andan increase in the average duration of the estrous cycle in this group. Therefore, doses 25 and 50 mg / kg of LdHshave been shown safe, however the dose 100 mg / kg decreased reproductive efficiency and promoted a lowsystemic toxicity as caused a decrease in feed consumption and interfered with the ponderable development.(AU)

Avaliação do ciclo estral e da toxicidade sistêmica do látex de Himatanthus sucuuba (Spruce) Woodson em ratas Wistar / The estrous cycle evaluation and systemic toxicity in the latex of Himatanthus sucuuba (Spruce) Woodson in Wistar rats

It aimed to investigate the possible effects induced by the diluted latex oral administration of H. sucuuba(LdHs) in Wistar rats on the estrous cycle and other organ systems. The Wistar rats received by gavage the LdHs.The results showed that there was a decrease in average daily intake and ponderable development negativeinterference in the group treated with the dose 100 mg / kg. The number of primary follicles and in the dose 100 mg/ kg LdHs was superior to the control group. It was also observed a decrease in the number of estrous cycles andan increase in the average duration of the estrous cycle in this group. Therefore, doses 25 and 50 mg / kg of LdHshave been shown safe, however the dose 100 mg / kg decreased reproductive efficiency and promoted a lowsystemic toxicity as caused a decrease in feed consumption and interfered with the ponderable development.

Efeito do óleo essencial dos frutos de aroeira vermelha (Schinus terebinthifolius Raddi) no período pré-implante de ratas prenhes / Effect of oil essential of aroeira vermelha (Schinus terebinthifolius Raddi) in period of pre-implantation of pregnant rats

Medicinal plants are important for supplying raw materials for the synthesis of drugs and may also betoxic. The species Schinus terebinthifolius Raddi, popularly known as aroeira red or pink pepper is widelyconsumed by many people. This study aimed to assess adverse effects of the essential oil from the fruits ofSchinus terebinthifolius on pregnancy, administered during the preimplantation period. We used 32 pregnantanimals divided into four groups, a control (Tween 80) and three treated oil at doses of 25mg / kg, 50mg / kgand 100mg / kg treated once daily, the first to the seventh day of pregnancy, orally. Statistically there was nodifference between the treated groups compared to pre-implant loss, but there was a statistically significantdifference with respect to the increased weight of the empty uterus, both in relative mass as absolute. It isconcluded that the rats treated with oil of mastic-red fruits showed signs of gestational toxicity.(AU)

Efeito do extrato etanólico de Simarouba versicolor em padrões reprodutivos de camundongos e no desenvolvimento embriofetal / Effect of ethanol extract of Simarouba versicolor in reproductive patterns of mice and embryo development

Simarouba versicolor has several proven biological activities, however little is known regarding effectson reproduction, so this study evaluated the effect of the ethanol extract of S. versicolor (EOH-Sv) embryofoetaldevelopment. It used to females pregnant randomly assigned into three groups receiving the extract of S.versicolor in doses of 5mg, 10mg and 20mg and a control group (-) received DMSO (3%) from the 8th to 12thday of gestation. The half of the fetuses was set at Bodian for visceral analysis, while the other half fixed informalin (5%) and subjected to alizarin red technique. The EOH-Sv at doses of 20 and 10mg caused abortionand death of the females and the dose of 5mg/kg was able to reduce the number of live fetuses compared tocontrols, there was an increase in the loss rate after implantation (46,03%) even with 90% of implantation. ThusEOH-Sv demonstrated maternal and fetal gestational toxicity.(AU)

Efeito do extrato etanólico de Simarouba versicolor em padrões reprodutivos de camundongos e no desenvolvimento embriofetal / Effect of ethanol extract of Simarouba versicolor in reproductive patterns of mice and embryo development

Simarouba versicolor has several proven biological activities, however little is known regarding effectson reproduction, so this study evaluated the effect of the ethanol extract of S. versicolor (EOH-Sv) embryofoetaldevelopment. It used to females pregnant randomly assigned into three groups receiving the extract of S.versicolor in doses of 5mg, 10mg and 20mg and a control group (-) received DMSO (3%) from the 8th to 12thday of gestation. The half of the fetuses was set at Bodian for visceral analysis, while the other half fixed informalin (5%) and subjected to alizarin red technique. The EOH-Sv at doses of 20 and 10mg caused abortionand death of the females and the dose of 5mg/kg was able to reduce the number of live fetuses compared tocontrols, there was an increase in the loss rate after implantation (46,03%) even with 90% of implantation. ThusEOH-Sv demonstrated maternal and fetal gestational toxicity.

Efeito do óleo essencial dos frutos de aroeira vermelha (Schinus terebinthifolius Raddi) no período pré-implante de ratas prenhes / Effect of oil essential of aroeira vermelha (Schinus terebinthifolius Raddi) in period of pre-implantation of pregnant rats

Medicinal plants are important for supplying raw materials for the synthesis of drugs and may also betoxic. The species Schinus terebinthifolius Raddi, popularly known as aroeira red or pink pepper is widelyconsumed by many people. This study aimed to assess adverse effects of the essential oil from the fruits ofSchinus terebinthifolius on pregnancy, administered during the preimplantation period. We used 32 pregnantanimals divided into four groups, a control (Tween 80) and three treated oil at doses of 25mg / kg, 50mg / kgand 100mg / kg treated once daily, the first to the seventh day of pregnancy, orally. Statistically there was nodifference between the treated groups compared to pre-implant loss, but there was a statistically significantdifference with respect to the increased weight of the empty uterus, both in relative mass as absolute. It isconcluded that the rats treated with oil of mastic-red fruits showed signs of gestational toxicity.

AVALIAÇÃO DA TOXICIDADE PERI E PÓS-NATAL (SEGMENTO III) DA OLEUROPEÍNA EM RATOS WISTAR

A oleuropeína é o composto fenólico majoritário nas folhas da oliveira e tem sido apontada como responsável pela maioria dos atributos terapêuticos da planta. Apesar dos inúmeros estudos a respeito dos benefícios da utilização da oliveira e seu composto majoritário, a oleuropeína, poucos são os dados na literatura referentes a sua toxicidade. Tendo em vista a importância de se verificar a toxicidade reprodutiva deste composto fenólico, nesse estudo foram investigados os efeitos da oleuropeína na prole de ratas Wistar, a partir da exposição durante os períodos de gestação e lactação as doses de 2000 mg/kg/dia (G1), 1000 mg/kg/dia (G2) e 500 mg/kg/dia (G3), e um grupo controle negativo que foi exposto a água destilada (CN). A progênie foi avaliada quanto ao seu desenvolvimento físico e sexual, por meio da observação visual das seguintes características: penugem, descolamento dos pavilhões auriculares, pelo, erupção dos dentes incisivos, abertura dos olhos, separação prepucial e abertura do canal vaginal. O desenvolvimento motor foi avaliado por meio de testes de reflexo, como: teste de endireitamento em superfície, geotaxia negativa e resposta ao agarrar. Foram realizados os testes de comportamento em campo aberto, para avaliação de ansiedade, e comportamento sexual, para avaliação de taxas reprodutivas. Foram analisados, ainda, o peso relativo dos órgãos e, nos machos, número e morfologia espermática. Os animais dos grupos G1 e G2 abriram os olhos mais tarde em comparação ao grupo controle (P<0,01), o G3 apresentou atraso no descolamento do pavilhão auricular (P<0,001), porém a característica de erupção de dentes incisivos foi precoce neste grupo em comparação ao grupo controle (P=0,023). Os animais do grupo G1 também apresentaram atraso na separação prepucial (P<0,001). No dia pós-natal 7 e 8 os animais dos grupos G1 e G2 demoraram mais para reorientarem-se no reflexo de geotaxia negativa (P<0,001), os mesmos grupos permaneceram menos tempo agarrados no 14º dia pósnatal (P<0,001). Os animais do grupo G1 (4,79 ±0,44) apresentaram uma maior porcentagem de anormalidades na morfologia espermática, em comparação ao grupo controle negativo (2,17±0,33). O G3 (27,09±3,63) também permaneceu mais tempo nos quadrantes centrais no teste de campo aberto quando comparado ao grupo controle (15,38±1,68). Nossos resultados demonstram que a exposição à oleuropeína interferiu no desenvolvimento físico e reprodutivo da progênie, o que limita sua recomendação durante os períodos gestacional e lactacional, especialmente em altas doses. Contribuindo com a elucidação de algumas questões referentes a segurança do seu uso como agente terapêutico. Palavras-chave: A oleuropeína é o composto fenólico majoritário nas folhas da oliveira e tem sido apontada como responsável pela maioria dos atributos terapêuticos da planta. Apesar dos inúmeros estudos a respeito dos benefícios da utilização da oliveira e seu composto majoritário, a oleuropeína, poucos são os dados na literatura referentes a sua toxicidade. Tendo em vista a importância de se verificar a toxicidade reprodutiva deste composto fenólico, nesse estudo foram investigados os efeitos da oleuropeína na prole de ratas Wistar, a partir da exposição durante os períodos de gestação e lactação as doses de 2000 mg/kg/dia (G1), 1000 mg/kg/dia (G2) e 500 mg/kg/dia (G3), e um grupo controle negativo que foi exposto a água destilada (CN). A progênie foi avaliada quanto ao seu desenvolvimento físico e sexual, por meio da observação visual das seguintes características: penugem, descolamento dos pavilhões auriculares, pelo, erupção dos dentes incisivos, abertura dos olhos, separação prepucial e abertura do canal vaginal. O desenvolvimento motor foi avaliado por meio de testes de reflexo, como: teste de endireitamento em superfície, geotaxia negativa e resposta ao agarrar. Foram realizados os testes de comportamento em campo aberto, para avaliação de ansiedade, e comportamento sexual, para avaliação de taxas reprodutivas. Foram analisados, ainda, o peso relativo dos órgãos e, nos machos, número e morfologia espermática. Os animais dos grupos G1 e G2 abriram os olhos mais tarde em comparação ao grupo controle (P<0,01), o G3 apresentou atraso no descolamento do pavilhão auricular (P<0,001), porém a característica de erupção de dentes incisivos foi precoce neste grupo em comparação ao grupo controle (P=0,023). Os animais do grupo G1 também apresentaram atraso na separação prepucial (P<0,001). No dia pós-natal 7 e 8 os animais dos grupos G1 e G2 demoraram mais para reorientarem-se no reflexo de geotaxia negativa (P<0,001), os mesmos grupos permaneceram menos tempo agarrados no 14º dia pósnatal (P<0,001). Os animais do grupo G1 (4,79 ±0,44) apresentaram uma maior porcentagem de anormalidades na morfologia espermática, em comparação ao grupo controle negativo (2,17±0,33). O G3 (27,09±3,63) também permaneceu mais tempo nos quadrantes centrais no teste de campo aberto quando comparado ao grupo controle (15,38±1,68). Nossos resultados demonstram que a exposição à oleuropeína interferiu no desenvolvimento físico e reprodutivo da progênie, o que limita sua recomendação durante os períodos gestacional e lactacional, especialmente em altas doses. Contribuindo com a elucidação de algumas questões referentes a segurança do seu uso como agente terapêutico.

Oleuropein is the major phenolic compound in olive leaves and has been identified as responsible for most of the plant's therapeutic attributes. Despite numerous studies on the benefits of using Olea europaea and its major compound, oleuropein, there are few data in the literature regarding its toxicity. In view of the importance of verifying the reproductive toxicity of this phenolic compound, in this study the effects of oleuropein on the offspring of Wistar rats were investigated, from the exposure during the gestation and lactation periods at doses of 2000 mg/kg/day (G1), 1000 mg/kg/day (G2) and 500 mg/kg/day (G3), and a negative control group that was exposed to distilled water (CN). The progeny was evaluated for their physical and sexual development, through visual observation of the following characteristics: fluff, detachment of the auricular pavilion, fur, eruption of incisor teeth, eye opening, preputial separation and opening of the vaginal canal. Motor development was evaluated through reflex tests, such as: surface straightening test, negative geotaxy and grapple test. Behavior tests in the open field, to assess anxiety, and sexual behavior, to evaluated reproductive rates, were performed. The relative organs weight and, in males, sperm number and morphology were also analyzed. The animalsin groups G1 and G2 opened their eyes later in comparison to the control group (P<0,01), G3 showed delay in the detachment of the auricular pavilion (P<0,001), however the incisor teeth eruption characteristic was early in this group compared to the control group (P=0,023). The animals in the G1 group also showed delay in the preputial separation (P<0,001). In the 7 and 8 postnatal day, the animals in the G1 and G2 groups took longer to reorient themselves in the geotaxis reflex (P<0,001), the same groups spent less time on the grapple test on the 14 postnatal day (P<0,001). The animals in the G1 (4,79 ±0,44) group showed a higher percentage of abnormalities in sperm morphology compared to the negative control group (2,17±0,33). The group G3 (27,09±3,63) also remained longer in the central quadrants in the open field test when compared to the control group (15,38±1,68). Our results demonstrate that exposure to oleuropein interfered with the progeny's physical and reproductive development, restricting its recommendation during gestational and lactational periods, especially in high doses. Contributing to the elucidation of some issues regarding the safety of its use as a therapeutic agent.

Reproductive toxicity assessment of Origanum vulgare essential oil on male Wistar rats

Background: The oregano essential oil (Origanum vulgare L.) is rich in phenolic compounds with therapeutic actionssuch as antimicrobial, antifungal and antioxidant. Based on the therapeutic potential and clinical use of oregano essentialoil, in vivo toxicology studies of oregano essential oil are scarce and the current researches focus on the genotoxicity ofseveral species of oregano; however, toxicological and complementary studies are needed to ensure safety of formulationscontaining this oil. Through values of Minimum Inhibitory Concentration (MIC) of oregano essential oil against Candidaspecies, and increased in an exponential scale, the initial dose was obtained. This study aims to evaluate male fertilitythrough the reproductive aspects of rats chronically treated with oregano essential oil.Materials, Methods & Results: The rats were divided into five groups with 10 males and 30 females each; three groupswere treated with oregano essential oil at a concentration of 3% Vol/Vol (GO3%), of 9% Vol/Vol (GO9%) and of 27% Vol/Vol (GO27%). The negative control group received the vehicle, 0.001% Vol/Vol Tween 80 (GC-) and the positive controlgroup was treated with thymol and terpinen-4-ol, at the same concentration found in the oregano essential oil, detected bygas chromatography (3% + 3% Vol/Vol) (GC+). Animals were allowed to adapt for at least ten days before the beginningof the experiment. They were maintained under...(AU)

Reproductive toxicity assessment of Origanum vulgare essential oil on male Wistar rats

Background: The oregano essential oil (Origanum vulgare L.) is rich in phenolic compounds with therapeutic actionssuch as antimicrobial, antifungal and antioxidant. Based on the therapeutic potential and clinical use of oregano essentialoil, in vivo toxicology studies of oregano essential oil are scarce and the current researches focus on the genotoxicity ofseveral species of oregano; however, toxicological and complementary studies are needed to ensure safety of formulationscontaining this oil. Through values of Minimum Inhibitory Concentration (MIC) of oregano essential oil against Candidaspecies, and increased in an exponential scale, the initial dose was obtained. This study aims to evaluate male fertilitythrough the reproductive aspects of rats chronically treated with oregano essential oil.Materials, Methods & Results: The rats were divided into five groups with 10 males and 30 females each; three groupswere treated with oregano essential oil at a concentration of 3% Vol/Vol (GO3%), of 9% Vol/Vol (GO9%) and of 27% Vol/Vol (GO27%). The negative control group received the vehicle, 0.001% Vol/Vol Tween 80 (GC-) and the positive controlgroup was treated with thymol and terpinen-4-ol, at the same concentration found in the oregano essential oil, detected bygas chromatography (3% + 3% Vol/Vol) (GC+). Animals were allowed to adapt for at least ten days before the beginningof the experiment. They were maintained under...

Effects of the association of beta-glucan and itraconazole on fertility of male Wistar rats / Efeitos da associação de beta-glucana e itraconazol sobre a fertilidade de ratos Wistar machos

Background: In recent years, the number of patients with systemic fungal infections requiring antifungal therapy has increased. As a consequence, antimicrobial resistance to conventional treatment is frequently reported. Due to this reason, new therapies emerge, including the combination of beta (1-3) glucan and itraconazole. However, the reproductive and fertility effects of this association were not known. So, the aim of this study was to identify the effects of the combination of itraconazole and beta (1-3) glucan, extracted from Saccharomyces cerevisiae, on male rats fertility. Materials, Methods & Results: Sixty male Wistar rats with 120-days-old were used. The experimental protocol was approved by Ethics Committee on Animal Use of the Federal University of Rio Grande do Sul (protocol CEUA/UFRGS no. 19452/2010). The animals were placed into six groups (n = 10 animals / group) as following: Negative Control group - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally and 0.25 mL of sterile normal saline (NaCl 0.9 %) subcutaneously weekly; Itraconazole (IT) group - treated daily with itraconazole solution at a dose of 10 mg.kg-1 orally and 0.25 mL of sterile 0.9% NaCl subcutaneously weekly; Beta group - treated daily with the volume corresponding to 10 mL. kg-1 of sterile distilled water orally and 0.5 mg of beta (1-3) glucan subcut

Nos últimos anos, observou-se aumento do número de pacientes com risco de infecções fúngicas sistêmicas, tais como portadores de HIV, distúrbios hematológicos graves ou imunossuprimidos, pacientes oncológicos e receptores de transplantes. Tais pacientes necessitam de antifúngicos tanto na forma terapêutica como preventiva. Em contrapartida a estes usos, tornaram-se frequentes os relatos de resistência aos fármacos mais utilizados, incluindo o itraconazol. Esta resistência é bastante relevante nos casos envolvendo o gênero Candida, e descrita com outros agentes, como Sporothrix schenckii e Aspergillus fumigatus, em humanos e animais. Nos casos de resistências aos antifúngicos tradicionais, novas alternativas terapêuticas foram buscadas; dentre essas, a associação de ß-glucana, estimulante do sistema imunológico, a antifúngicos tradicionais, mostram-se promissora. Contudo, não existem estudos sobre os efeitos dessa associação sobre o sistema reprodutivo. [...]

Efeitos da associação de beta-glucana e itraconazol sobre a fertilidade de ratos Wistar machos / Effects of the Association of Beta-glucan and Itraconazole on Fertility of Male Wistar Rats

Background: In recent years, the number of patients with systemic fungal infections requiring antifungal therapy has increased. As a consequence, antimicrobial resistance to conventional treatment is frequently reported. Due to this reason, new therapies emerge, including the combination of beta (1-3) glucan and itraconazole. However, the reproductive and fertility effects of this association were not known. So, the aim of this study was to identify the effects of the combination of itraconazole and beta (1-3) glucan, extracted from Saccharomyces cerevisiae, on male rats fertility. Materials, Methods & Results: Sixty male Wistar rats with 120-days-old were used. The experimental protocol was approved by Ethics Committee on Animal Use of the Federal University of Rio Grande do Sul (protocol CEUA/UFRGS no. 19452/2010). The animals were placed into six groups (n = 10 animals / group) as following: Negative Control group - treated daily with the volume corresponding to 10 mL.kg-¹ of sterile distilled water orally and 0.25 mL of sterile normal saline (NaCl 0.9 %) subcutaneously weekly; Itraconazole (IT) group - treated daily with itraconazole solution at a dose of 10 mg.kg-¹ orally and 0.25 mL of sterile 0.9% NaCl subcutaneously weekly; Beta group - treated daily with the volume corresponding to 10 mL.kg-¹ of sterile distilled water orally and 0.5 mg of beta (1-3) glucan subcutaneously weekly; Therapeutic Dose (TD) group - daily treated with itraconazole at a dose of 10 mg.kg-¹ orally and 0.5 mg of ß (1-3) glucan subcutaneously weekly; TD5x - treated daily with itraconazole at a dose of 50 mg.kg-¹ orally and 0.5 mg of beta (1-3 ) glucan subcutaneously weekly; TD10x - daily treated with itraconazole at a dose of 100 mg.kg-¹ orally and 0.5 mg of beta (1-3) glucan subcutaneously weekly. The rats were treated for 91 consecutive days. Individual body mass, organs relative mass and histopathology, number of sperm in the cauda epididymis, daily spermatozoal production, sperm parameters, sperm morphology, serum testosterone concentration and reproductive rates were evaluated. Significant differences were observed in daily spermatozoal production, sperm morphology, serum concentration of testosterone, mating rate and birth rate, with lower results in the TD5x and TD10x groups. Discussion: The systemic toxicity indicators, as body mass variation, water intake and clinical signs, as well as organ histology suggest that systemic toxicity in these animals did not occur. The decrease in serum testosterone concentrations in elevated doses of itraconazole associated with beta (1-3) glucan must be involved in decrease of sperm parameters and in sexual behavior and consequently, in the reproductive rates. Changes in sperm morphology, mainly found in sperm head, indicate sperm immaturity, preamature spermiation, abnormal or degenerate acrosome. Based on these results, it is concluded that beta (1-3) glucan and itraconazole did not affect the male rats reproductive variables when used in therapeutic doses alone or in combination, however these variables were altered with higher doses of itraconazole in the association. These data, added to the absence of histopathological damage of the testes suggest functional effect on male fertility. Caution is advised in the use of high doses of itraconazole with or without beta (1-3) glucan in males, especially in prolonged therapy.

Effects of the association of beta-glucan and itraconazole on fertility of male Wistar rats / Efeitos da associação de beta-glucana e itraconazol sobre a fertilidade de ratos Wistar machos

Background: In recent years, the number of patients with systemic fungal infections requiring antifungal therapy has increased. As a consequence, antimicrobial resistance to conventional treatment is frequently reported. Due to this reason, new therapies emerge, including the combination of beta (1-3) glucan and itraconazole. However, the reproductive and fertility effects of this association were not known. So, the aim of this study was to identify the effects of the combination of itraconazole and beta (1-3) glucan, extracted from Saccharomyces cerevisiae, on male rats fertility. Materials, Methods & Results: Sixty male Wistar rats with 120-days-old were used. The experimental protocol was approved by Ethics Committee on Animal Use of the Federal University of Rio Grande do Sul (protocol CEUA/UFRGS no. 19452/2010). The animals were placed into six groups (n = 10 animals / group) as following: Negative Control group - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally and 0.25 mL of sterile normal saline (NaCl 0.9 %) subcutaneously weekly; Itraconazole (IT) group - treated daily with itraconazole solution at a dose of 10 mg.kg-1 orally and 0.25 mL of sterile 0.9% NaCl subcutaneously weekly; Beta group - treated daily with the volume corresponding to 10 mL. kg-1 of sterile distilled water orally and 0.5 mg of beta (1-3) glucan subcut

Nos últimos anos, observou-se aumento do número de pacientes com risco de infecções fúngicas sistêmicas, tais como portadores de HIV, distúrbios hematológicos graves ou imunossuprimidos, pacientes oncológicos e receptores de transplantes. Tais pacientes necessitam de antifúngicos tanto na forma terapêutica como preventiva. Em contrapartida a estes usos, tornaram-se frequentes os relatos de resistência aos fármacos mais utilizados, incluindo o itraconazol. Esta resistência é bastante relevante nos casos envolvendo o gênero Candida, e descrita com outros agentes, como Sporothrix schenckii e Aspergillus fumigatus, em humanos e animais. Nos casos de resistências aos antifúngicos tradicionais, novas alternativas terapêuticas foram buscadas; dentre essas, a associação de ß-glucana, estimulante do sistema imunológico, a antifúngicos tradicionais, mostram-se promissora. Contudo, não existem estudos sobre os efeitos dessa associação sobre o sistema reprodutivo. [...]