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Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):346-351
DOI 10.1590/S0100-72032007000700004
PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological changes than the ones of Exp60. Regarding the fetal organs, no histomorphological abnormalities were observed in all the groups. CONCLUSIONS: our results show that the administration of Ritonavir to pregnant rats, in higher than conventional doses causes morphological changes in the maternal liver and kidneys. On the other hand, the lack of abnormalities in the fetal organs may be due to the protective role of glycoprotein P.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):346-351
DOI 10.1590/S0100-72032007000700004
PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological changes than the ones of Exp60. Regarding the fetal organs, no histomorphological abnormalities were observed in all the groups. CONCLUSIONS: our results show that the administration of Ritonavir to pregnant rats, in higher than conventional doses causes morphological changes in the maternal liver and kidneys. On the other hand, the lack of abnormalities in the fetal organs may be due to the protective role of glycoprotein P.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2000;22(2):107-111
DOI 10.1590/S0100-72032000000200008
Purpose: the aim of the present work was to study the chronic action of the antiemetic domperidone on the pregnancy of albino rats. Methods: fifty albino, pregnant Wistar rats were randomly allocated to five groups: GI (control I) = intact rats; GII (control II) = rats receiving the drug vehicle (distilled water) by gavage at the same schedule of the experimental groups; rats in groups GIII, GIV and GV were treated with domperidone by gavage, 2, 6 and 12 mg/kg per day, respectively, divided into 4 daily doses, always in 1 ml of distilled water, from time zero up to the 20th day of pregnancy. The evolution of body weight gain was followed throughout and the animals were sacrificed at term (20th day) by deep ether anesthesia. Number of fetuses, placenta and implantation sites, placenta and fetus weight, fetal malformations and maternal and fetal mortality were evaluated. Results: we observed only intrauterine fetal mortality with 14, 26 and 32 in 74, 60 and 57 newborns of the groups III, IV and V, respectively. Conclusion: though the results of animal experimentation cannot directly be transposed to human conditions, this paper calls attention to the need for a safe judgement when prescribing domperidone to a first-trimester pregnant patient in order to reduce her emetic crises.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2000;22(2):107-111
DOI 10.1590/S0100-72032000000200008
Purpose: the aim of the present work was to study the chronic action of the antiemetic domperidone on the pregnancy of albino rats. Methods: fifty albino, pregnant Wistar rats were randomly allocated to five groups: GI (control I) = intact rats; GII (control II) = rats receiving the drug vehicle (distilled water) by gavage at the same schedule of the experimental groups; rats in groups GIII, GIV and GV were treated with domperidone by gavage, 2, 6 and 12 mg/kg per day, respectively, divided into 4 daily doses, always in 1 ml of distilled water, from time zero up to the 20th day of pregnancy. The evolution of body weight gain was followed throughout and the animals were sacrificed at term (20th day) by deep ether anesthesia. Number of fetuses, placenta and implantation sites, placenta and fetus weight, fetal malformations and maternal and fetal mortality were evaluated. Results: we observed only intrauterine fetal mortality with 14, 26 and 32 in 74, 60 and 57 newborns of the groups III, IV and V, respectively. Conclusion: though the results of animal experimentation cannot directly be transposed to human conditions, this paper calls attention to the need for a safe judgement when prescribing domperidone to a first-trimester pregnant patient in order to reduce her emetic crises.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2001;23(2):113-117
DOI 10.1590/S0100-72032001000200009
Purpose: to examine the effects of tramadol hydrochloride on rat pregnancy. Methods: five groups of 10 pregnant albino rats each were treated from the 1st up to the 20th day of pregnancy as follows: GI = intact controls; GII = controls which received 0.5 ml of distilled water (drug vehicle) once a day by gavage; GIII, GIV and GV = groups treated respectively with 6.7, 20.1 or 45.6 mg/kg of tramadol hydrochloride once a day by gavage in a final volume of 0.5 mL. Body weight gain was monitored by weighing at the beginning and on the 7th, 14th and 20th day of pregnancy. At term the animals were killed under deep ether anesthesia and the following parameters were evaluated: number of implantations, of resorptions, of viable fetuses and of placentae; presence of major malformations; maternal and fetal mortality and weights of fetuses and placentae. Results: tramadol significantly affected maternal body weight gain, this effect being more apparent in groups IV and V (mean reductions of weight gain of 41 and 56%, respectively). In group III the weight gain was affected more at days 7 and 14 (33% mean gain reductions) than at day 20 (19%). Drug treatment affected significantly and in a dose-dependent fashion the following parameters: individual weight of fetuses (GV = -39.2%), offspring weight (GIV = -51.7%; GV = -44.2%), number of placentae (GIV = -28.4%; GV = -11.6%), individual weight of placentae (GV = -10%) and the total weight of placentae (GIV = -28.4%; GV = -16.8%). Though among the treated animals there was an increase in resorptions and deaths at birth, these events were not significantly different from those found in controls. Conclusions: Tramadol showed definite deleterious effects on albino rat pregnancy, and these effects were exerted not only on the maternal but also the on fetal organisms. Overall, the effects were more pronounced at the 14th than at the 20th day of pregnancy, thus suggesting that the organogenic phase of the fetus is more susceptible than its initial (embryogenic) or final (term) phases. The results call attention to the care which is to be taken when the use of this opioid is considered during pregnancy.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2001;23(2):113-117
DOI 10.1590/S0100-72032001000200009
Purpose: to examine the effects of tramadol hydrochloride on rat pregnancy. Methods: five groups of 10 pregnant albino rats each were treated from the 1st up to the 20th day of pregnancy as follows: GI = intact controls; GII = controls which received 0.5 ml of distilled water (drug vehicle) once a day by gavage; GIII, GIV and GV = groups treated respectively with 6.7, 20.1 or 45.6 mg/kg of tramadol hydrochloride once a day by gavage in a final volume of 0.5 mL. Body weight gain was monitored by weighing at the beginning and on the 7th, 14th and 20th day of pregnancy. At term the animals were killed under deep ether anesthesia and the following parameters were evaluated: number of implantations, of resorptions, of viable fetuses and of placentae; presence of major malformations; maternal and fetal mortality and weights of fetuses and placentae. Results: tramadol significantly affected maternal body weight gain, this effect being more apparent in groups IV and V (mean reductions of weight gain of 41 and 56%, respectively). In group III the weight gain was affected more at days 7 and 14 (33% mean gain reductions) than at day 20 (19%). Drug treatment affected significantly and in a dose-dependent fashion the following parameters: individual weight of fetuses (GV = -39.2%), offspring weight (GIV = -51.7%; GV = -44.2%), number of placentae (GIV = -28.4%; GV = -11.6%), individual weight of placentae (GV = -10%) and the total weight of placentae (GIV = -28.4%; GV = -16.8%). Though among the treated animals there was an increase in resorptions and deaths at birth, these events were not significantly different from those found in controls. Conclusions: Tramadol showed definite deleterious effects on albino rat pregnancy, and these effects were exerted not only on the maternal but also the on fetal organisms. Overall, the effects were more pronounced at the 14th than at the 20th day of pregnancy, thus suggesting that the organogenic phase of the fetus is more susceptible than its initial (embryogenic) or final (term) phases. The results call attention to the care which is to be taken when the use of this opioid is considered during pregnancy.
