Comparative neurotoxicity of iobitridol with iohexol by intracisternal administration in Wistar rats / Neurotoxicidade comparativa do iobitridol com o iohexol, por via intracisternal, em ratos Wistar

Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comparable to that observed with iohexol. Further study with dogs and cats, as an alternative, is suggested.(AU)

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol demonstrou baixa neurotoxicidade, comparável a observada com o iohexol. Sugerem-se mais estudos com cães e gatos para utilização do iobitridol como alternativa.(AU)

Pre- and postnatal evaluation of offspring rats exposed to Origanum vulgare essential oil during mating, gestation and lactation / Avaliação pré e pós-natal da prole de ratos expostos ao óleo essencial de Origanum vulgare durante acasalamento, gestação e lactação

Despite the increasing use of oregano (Origanum vulgare L.) essential oil for therapeutic purposes, pre- and postnatal development of animals offspring exposed to this oil has not yet been evaluated. In line with previous concerns of genotoxicity, in this study adult rats were exposed to different doses of oregano essential oil (3, 9 and 27% vol/vol) during pre-mating, mating, gestation and lactation. Prenatal screening included fetal development and uterine inspection, where the reproductive rate of females such as breeding, pregnancy, delivery, viability and post-implantation loss rate were measured. Postnatal evaluation of rat offspring included motor development, neuroendocrine and behavioral assessment. Body weight of rat dams and signs of dystocia were evaluated daily. Development of physic characteristics and reflex tests of puppies were also assessed. Additionally, these rats, when adults, were submitted to sexual and open field behavioral tests. The main differences among the groups were observed in the indices of mating, pregnancy and post-implantation loss (P < 0.01). Results demonstrated that the treatment of parental generation with oregano essential oil has the potential to affect the developing fetuses at the highest dose used, but without causing maternal toxicity and changes in general behavior and development of the progeny.

Apesar do aumento do uso do óleo essencial de orégano (Origanum vulgare L.) para fins terapêuticos, o desenvolvimento pré e pós-natal da progênie de animais expostos a este óleo ainda não foi avaliado. Partindo das suspeitas prévias de genotoxicidade desse óleo, neste estudo, ratos Wistar adultos foram expostos a diferentes doses do óleo essencial de orégano (3, 9 e 27% vol/vol) durante o acasalamento, a gestação e a lactação. Para a avaliação pré-natal, o desenvolvimento gestacional foi observado e os úteros inspecionados, assim como os índices reprodutivos das fêmeas, como a taxa de acasalamento, de gestação, parto e perdas pós-implantação. Na avaliação pós-natal, observou-se o desenvolvimento motor, neuroendócrino e comportamental da prole. Observou-se, diariamente, o peso das ratas e sinais de distocia. Após o parto, as características de desenvolvimento e testes de reflexos dos filhotes foram avaliadas, enquanto que, na puberdade, foram realizadas análises histopatológicas e dosagem hormonal. Adicionalmente, na idade adulta, esses ratos foram submetidos ao teste de comportamento em campo aberto e ao comportamento sexual. As principais diferenças entre os grupos foram nos índices de acasalamento, de gestação e de perdas pós-implantação (P < 0,01). Os resultados demonstram que o tratamento da geração parental com óleo essencial de orégano tem potencial para afetar os índices reprodutivos das ratas e o desenvolvimento dos fetos na maior dose utilizada, mas sem causar toxicidade materna e alterações no desenvolvimento geral e comportamental da sua progênie.

Pre- and postnatal evaluation of offspring rats exposed to Origanum vulgare essential oil during mating, gestation and lactation / Avaliação pré e pós-natal da prole de ratos expostos ao óleo essencial de Origanum vulgare durante acasalamento, gestação e lactação

Despite the increasing use of oregano (Origanum vulgare L.) essential oil for therapeutic purposes, pre- and postnatal development of animals offspring exposed to this oil has not yet been evaluated. In line with previous concerns of genotoxicity, in this study adult rats were exposed to different doses of oregano essential oil (3, 9 and 27% vol/vol) during pre-mating, mating, gestation and lactation. Prenatal screening included fetal development and uterine inspection, where the reproductive rate of females such as breeding, pregnancy, delivery, viability and post-implantation loss rate were measured. Postnatal evaluation of rat offspring included motor development, neuroendocrine and behavioral assessment. Body weight of rat dams and signs of dystocia were evaluated daily. Development of physic characteristics and reflex tests of puppies were also assessed. Additionally, these rats, when adults, were submitted to sexual and open field behavioral tests. The main differences among the groups were observed in the indices of mating, pregnancy and post-implantation loss (P < 0.01). Results demonstrated that the treatment of parental generation with oregano essential oil has the potential to affect the developing fetuses at the highest dose used, but without causing maternal toxicity and changes in general behavior and development of the progeny.(AU)

Apesar do aumento do uso do óleo essencial de orégano (Origanum vulgare L.) para fins terapêuticos, o desenvolvimento pré e pós-natal da progênie de animais expostos a este óleo ainda não foi avaliado. Partindo das suspeitas prévias de genotoxicidade desse óleo, neste estudo, ratos Wistar adultos foram expostos a diferentes doses do óleo essencial de orégano (3, 9 e 27% vol/vol) durante o acasalamento, a gestação e a lactação. Para a avaliação pré-natal, o desenvolvimento gestacional foi observado e os úteros inspecionados, assim como os índices reprodutivos das fêmeas, como a taxa de acasalamento, de gestação, parto e perdas pós-implantação. Na avaliação pós-natal, observou-se o desenvolvimento motor, neuroendócrino e comportamental da prole. Observou-se, diariamente, o peso das ratas e sinais de distocia. Após o parto, as características de desenvolvimento e testes de reflexos dos filhotes foram avaliadas, enquanto que, na puberdade, foram realizadas análises histopatológicas e dosagem hormonal. Adicionalmente, na idade adulta, esses ratos foram submetidos ao teste de comportamento em campo aberto e ao comportamento sexual. As principais diferenças entre os grupos foram nos índices de acasalamento, de gestação e de perdas pós-implantação (P < 0,01). Os resultados demonstram que o tratamento da geração parental com óleo essencial de orégano tem potencial para afetar os índices reprodutivos das ratas e o desenvolvimento dos fetos na maior dose utilizada, mas sem causar toxicidade materna e alterações no desenvolvimento geral e comportamental da sua progênie.(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...(AU)

Toxicidade reprodutiva da associação de itraconazol e beta-glucana em ratas e sua progênie / Reproductive toxicity of itraconazole in combination with beta-glucan in female rats and their offspring

Background: Reports of yeast isolates resistant to traditional antifungal drugs have become common. Similarly, refractory clinical cases treated with these traditional antifungal drugs have also been reported. These cases ‘may or may not be related to pregnancy. Newly developed therapeutic approaches, such as the immunostimulant β-glucan combined with the traditional antifungal agents show promising results. Therefore, knowledge of the effects of these new associations is essential. The aims of this study were to evaluate the effects of the combination of itraconazole and β (1-3) glucan on fertility in female rats and its interference in the development of their offspring, including teratogenic potential.Materials, Methods & Results: A total of 180 female Wistar rats (90 days old) separated into six groups were used (n = 30 per group): Negative Control - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.25 mL of sterile 0.9% NaCl solution subcutaneously weekly; IT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.25 ml of sterile 0.9% NaCl solution subcutaneously weekly; Beta - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT5x - treated daily with itraconazole at a dose of 50 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT10x - treated daily with itraconazole at a dose of 100 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly. The rats were treated before (14 days) and during the mating period (up to 21 days), pregnancy (21 days) and lactation (21 days).[...](AU)

Toxicidade reprodutiva da associação de itraconazol e beta-glucana em ratas e sua progênie / Reproductive toxicity of itraconazole in combination with beta-glucan in female rats and their offspring

Background: Reports of yeast isolates resistant to traditional antifungal drugs have become common. Similarly, refractory clinical cases treated with these traditional antifungal drugs have also been reported. These cases ‘may or may not be related to pregnancy. Newly developed therapeutic approaches, such as the immunostimulant β-glucan combined with the traditional antifungal agents show promising results. Therefore, knowledge of the effects of these new associations is essential. The aims of this study were to evaluate the effects of the combination of itraconazole and β (1-3) glucan on fertility in female rats and its interference in the development of their offspring, including teratogenic potential.Materials, Methods & Results: A total of 180 female Wistar rats (90 days old) separated into six groups were used (n = 30 per group): Negative Control - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.25 mL of sterile 0.9% NaCl solution subcutaneously weekly; IT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.25 ml of sterile 0.9% NaCl solution subcutaneously weekly; Beta - treated daily with the volume corresponding to 10 mL.kg-1 of sterile distilled water orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT - treated daily with itraconazole at a dose of 10 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT5x - treated daily with itraconazole at a dose of 50 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly; DT10x - treated daily with itraconazole at a dose of 100 mg.kg-1 orally, and 0.5 mg of β (1-3) glucan subcutaneously weekly. The rats were treated before (14 days) and during the mating period (up to 21 days), pregnancy (21 days) and lactation (21 days).[...]

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...

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.

Efeitos dos fitoestrógenos da soja sobrea fertilidade humana e animal: revisão bibliográfica / Effect of the phytoestrogens of the soy on the fertility human and animal

A soja é uma leguminosa pertencente à família Fabaceae, rica em fitoquímicos, em espe¬cial as isoflavonas. Pertencentes à família dos polifenóis, as isoflavonas da soja por sua seme¬lhança estrutural ao estrógeno humano, determinam efeitos estrogênicos importantes, sendo por isso referida como fitoestrógenos. Há numerosa literatura referente aos usos da soja para a prevenção e tratamento de doenças. As principais indicações terapêuticas são: substituição do leite animal em crianças com manifestações alérgicas, tratamento de sintomas pré e pós-meno¬pausa na prevenção da osteoporose, na prevenção e tratamento de câncer, na prevenção de doenças cardiovasculares e como auxiliar no tratamento de diabetes. No entanto existem muitos estudos contraditórios que revelam efeitos de toxicidade das isoflavonas sobre a fertilidade

Soybean is a leguminous species of the Fabaceae family rich in phytochemical compounds, especially isoflavones, are members of the polyphenol group and their chemical structure is closely related to human estrogen; they are capable of inducing marked hormonal effects, and are named phytoestrogens. There is an extensive literature covering the use of soybean for prevention and treatment of several diseases. The therapeutical indications include: substitution of milk in allergic children, management of pre and post-menopausal symptoms, prevention of osteoporosis, prevention and treatment of cancer, prevention of cardiovascular diseases and as an adjuvant to the diabetes treatment. However, many contradictory studies report toxic effects of isoflavones on fertility

Efeitos dos fitoestrógenos da soja sobrea fertilidade humana e animal: revisão bibliográfica / Effect of the phytoestrogens of the soy on the fertility human and animal

A soja é uma leguminosa pertencente à família Fabaceae, rica em fitoquímicos, em espe¬cial as isoflavonas. Pertencentes à família dos polifenóis, as isoflavonas da soja por sua seme¬lhança estrutural ao estrógeno humano, determinam efeitos estrogênicos importantes, sendo por isso referida como fitoestrógenos. Há numerosa literatura referente aos usos da soja para a prevenção e tratamento de doenças. As principais indicações terapêuticas são: substituição do leite animal em crianças com manifestações alérgicas, tratamento de sintomas pré e pós-meno¬pausa na prevenção da osteoporose, na prevenção e tratamento de câncer, na prevenção de doenças cardiovasculares e como auxiliar no tratamento de diabetes. No entanto existem muitos estudos contraditórios que revelam efeitos de toxicidade das isoflavonas sobre a fertilidade(AU)

Soybean is a leguminous species of the Fabaceae family rich in phytochemical compounds, especially isoflavones, are members of the polyphenol group and their chemical structure is closely related to human estrogen; they are capable of inducing marked hormonal effects, and are named phytoestrogens. There is an extensive literature covering the use of soybean for prevention and treatment of several diseases. The therapeutical indications include: substitution of milk in allergic children, management of pre and post-menopausal symptoms, prevention of osteoporosis, prevention and treatment of cancer, prevention of cardiovascular diseases and as an adjuvant to the diabetes treatment. However, many contradictory studies report toxic effects of isoflavones on fertility(AU)

Comparative neurotoxicity of iobitridol with iohexol by intracisternal administration in Wistar rats / Neurotoxicidade comparativa do iobitridol com o iohexol, por via intracisternal, em ratos Wistar

Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comparable to that observed with iohexol. Further study with dogs and cats, as an alternative, is suggested.

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol demonstrou baixa neurotoxicidade, comparável a observada com o iohexol. Sugerem-se mais estudos com cães e gatos para utilização do iobitridol como alternativa.

Comparative neurotoxicity of iobitridol with iohexol by intracisternal administration in Wistar rats / Neurotoxicidade comparativa do iobitridol com o iohexol, por via intracisternal, em ratos Wistar

Iobitridol is a tri-iodinated contrast agent, and neurotoxicologic studies of the intracisternal administration are scarce and inconclusive. The purpose of this study was to compare the neurotoxicity of iobitridol with iohexol, by intracisternal administration in Wistar rats, for a pre-clinical evaluation of its use as a myelographic agent. The animals, a total of 75, were divided into three experimental groups, iobitridol, iohexol and cerebral artificial fluid (control group), with 25 animals per group. Then, these were divided into five subgroups of five animals each, and given doses of 200, 400, 600, 800 and 1000 mg kg-1, while the control group received the equivalent volumes of contrast media tested. The animals were evaluated after 5, 15, 30, 60, 120, 180 and 240 min of intracisternal administration of these substances, for signs of depression and excitement, tactile palmar grasp, flexor, extensor, palpebral, papillary and pinna reflexes, surface righting and placing reactions, and with an auditory startle test. The evaluations were assessed daily for seven days with these parameters and their body weight, food, and water intake were also measured. There were no statistically significant differences between groups tested with respect to any of the evaluated parameters. In other words, in this animal model, the iobitridol demonstrated a low neurotoxicologic potential, comp

O iobitridol é um meio de contraste tri-iodado, e estudos referentes à neurotoxicidade, com administração subaracnóide são escassos e inconclusivos. O objetivo deste trabalho foi comparar a neurotoxicidade do iobitridol com a do iohexol, por via intracisternal, em ratos Wistar, como avaliação pré-clínica da utilização deste como agente mielográfico. Foram utilizados 75 animais divididos em três grupos experimentais com 25 animais: iobitridol, iohexol e líquido cerebroespinhal artificial (grupo controle). Estes foram subdivididos em cinco subgrupos com cinco animais cada, com doses distintas de 200, 400, 600, 800 e 1000 mg kg-1, sendo utilizado no grupo controle o volume equivalente aos meios de contraste testados. Os animais foram avaliados após 5, 15, 30, 60, 120, 180 e 240 min da administração intracisternal dessas substâncias, quanto a sinais de depressão e excitação, reflexos tátil de agarramento palmar, flexor, extensor, palpebral, pupilar e da pina, reação de endireitamento e posicionamento e resposta auditiva. Nos sete dias subsequentes, os animais foram avaliados diariamente quanto a estes parâmetros, e ainda a massa corporal, a ingestão de ração e de água, foram mensuradas. Não foram observadas diferenças estatisticamente significativas entre os grupos testados com meios de contraste, em nenhum dos parâmetros avaliados. Dessa forma, nesse modelo animal, o iobitridol de