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Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(11):556-562
DOI 10.1590/S0100-72032010001100007
PURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10% formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(11):556-562
DOI 10.1590/S0100-72032010001100007
PURPOSE: to evaluate the effect of administration of three different doses of the zidovudine/lamivudine/ritonavir combination on the liver and kidneys of pregnant rats and their concepts from a morphological and physiological standpoint. METHODS: 40 pregnant EPM-1 Wistar rats were randomly divided into 4 groups: 1 control (Ctrl: drug vehicle control, n=10) and 3 experimental groups: Exp1x, Exp3x and Exp9x. An oral solution of the zidovudine/lamivudine/ritonavir combination was administered to the experimental groups from the day 0 to day 20 of pregnancy: Exp1x=10/5/20 mg/kg; Exp3x=30/15/60 mg/kg; Exp9x=90/45/180 mg/kg. On the 20th pregnancy day the rats were anesthetized and blood was taken directly from the ventricular chambers for further biochemical determinations: aspartate-(AST) and alanine-(ALT) aminotransferases (Calorimetric method), urea nitrogen (BUN) by an enzymatic-kinetic method, and creatinine by a kinetic-calorimetric method. Maternal and fetal liver and kidney samples were taken, fixed in 10% formaldehyde and processed histologically for paraffin embedding. Five µm-thick fragments of maternal and fetal livers and kidneys were stained with hematoxilyn-eosin, being analyzed by light microscopy. To interpret the results, the well-known pattern of normality for livers and kidneys was considered on the basis of the following structures: hepatocytes, portal structure, hepatic veins, renal corpuscles, renal tubules and loop of Henle. Regarding the fetal livers, we also considered the erythrocytes in their different stages of development as well as the megacariocytes. If there was a change in the established staining pattern for liver and kidney structures, changes in nuclear morphology, rupture of some cytoplasmic organelles, and presence of vascular congestion, this was considered to be due to the drug doses. Results were submitted to analysis of variance (ANOVA) and to the Tukey-Kramer multiple comparisons test (p<0.05). RESULTS: no morphological changes were observed in the maternal livers of the Ctrl, Exp1x and Exp3x groups. In the maternal liver of the Exp9x group, hepatocytes showed signs of atrophy and apoptosis (eosinophilic cytoplasm and pycnotic nuclei) and marked sinusoid capillary vasodilation (congestion) was observed. The maternal kidneys of the Ctrl and Exp1x groups were normal, with renal corpuscles, convoluted tubules and typical loops of Henle. In contrast, the Exp3x and Exp9x groups showed vascular congestion and small glomeruli rich in cells containing hyperchromatic nuclei which were more intense in Exp9x. Regarding the fetal organs, no morphological or physiological changes were observed. A significant increase of AST (305.70±55.80, p<0.05) and creatinine (0.50±0.09, p<0.05) was observed in group Exp9x. CONCLUSIONS: our results show that the administration of the zidovudine, lamivudine and ritonavir combination to pregnant rats at high doses caused morphological and physiological changes in the maternal liver and kidneys. On the other hand, there were no changes in fetal organs.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(2):67-70
DOI 10.1590/S0100-72031998000200002
The purpose of this study is to evaluate the effects of propoxyphene napsylate on the pregnancy of the rat. We used fifty pregnant rats divided into five groups. All the animals received daily 1 ml of the solution by gavage from day 0 to the 20th day of pregnancy. Group I - only distilled water (control); group II - aqueous solution of acacia 2% (vehicle); groups III, IV and V - respectively, 5, 15 and 45 mg/kg of weight of propoxyphene napsylate diluted in 2% acacia solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. All animals were sacrificed on the 20th day of pregnancy. Our results showed that the animals treated with 45 mg/kg of propoxyphene napsylate presented reduction of the individual weights of the fetuses, as well as of the weights of the newborns and placentas. The difference betewwn number of resorptions, implantations and placentas of the treated groups was shown to be non significant cohen compered with the control groups.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(2):67-70
DOI 10.1590/S0100-72031998000200002
The purpose of this study is to evaluate the effects of propoxyphene napsylate on the pregnancy of the rat. We used fifty pregnant rats divided into five groups. All the animals received daily 1 ml of the solution by gavage from day 0 to the 20th day of pregnancy. Group I - only distilled water (control); group II - aqueous solution of acacia 2% (vehicle); groups III, IV and V - respectively, 5, 15 and 45 mg/kg of weight of propoxyphene napsylate diluted in 2% acacia solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. All animals were sacrificed on the 20th day of pregnancy. Our results showed that the animals treated with 45 mg/kg of propoxyphene napsylate presented reduction of the individual weights of the fetuses, as well as of the weights of the newborns and placentas. The difference betewwn number of resorptions, implantations and placentas of the treated groups was shown to be non significant cohen compered with the control groups.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(5):245-249
DOI 10.1590/S0100-72031998000500003
The purpose of the present study was to evaluate the effects of acetylsalicylic acid (ASA) on the pregnancy of female albino rats. We used 60 pregnant female rats which were divided into six groups of ten cache. All the animals received daily by gavage, from the 5th (day zero) until the 20th day of pregnancy, 1 ml of the following: Group I - only distilled water (control); Group II - 0.2% aqueous solution of carboxymethylcellulose (vehicle); Groups III, IV, V and VI - 1, 10, 100 and 400 mg/kg body weight respectively, of ASA diluted in 0.2% carboxymethylcellulose solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. Our results showed that the animals treated with 100 mg of ASA presented a reduction in the number of live newborns. The animals treated with 400 mg/kg/day presented not only a reduction in the number of live newborns but also decrease in maternal, newborn and placental weight.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 1998;20(5):245-249
DOI 10.1590/S0100-72031998000500003
The purpose of the present study was to evaluate the effects of acetylsalicylic acid (ASA) on the pregnancy of female albino rats. We used 60 pregnant female rats which were divided into six groups of ten cache. All the animals received daily by gavage, from the 5th (day zero) until the 20th day of pregnancy, 1 ml of the following: Group I - only distilled water (control); Group II - 0.2% aqueous solution of carboxymethylcellulose (vehicle); Groups III, IV, V and VI - 1, 10, 100 and 400 mg/kg body weight respectively, of ASA diluted in 0.2% carboxymethylcellulose solution. The animals were weighed on days 0, 7, 14 and 20 of pregnancy. Our results showed that the animals treated with 100 mg of ASA presented a reduction in the number of live newborns. The animals treated with 400 mg/kg/day presented not only a reduction in the number of live newborns but also decrease in maternal, newborn and placental weight.
