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Artigos Originais
Morphological and physiological analysis of livers and kidneys of pregnant rats and their fetuses treated by the association of zidovudine, lamivudine and ritonavir for the whole period of pregnancy
- Adriana Wagner,
- Adelino Moreira de Carvalho,
- Mary Uchiyama Nakamura,
- Ricardo Santos Simões,
- Tereza Maria Pereira Fontes, [ ... ],
- Luiz Kulay Júnior
01-20-2010
Summary
Artigos OriginaisMorphological and physiological analysis of livers and kidneys of pregnant rats and their fetuses treated by the association of zidovudine, lamivudine and ritonavir for the whole period of pregnancy
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(11):556-562
01-20-2010DOI 10.1590/S0100-72032010001100007
- Adriana Wagner,
- Adelino Moreira de Carvalho,
- Mary Uchiyama Nakamura,
- Ricardo Santos Simões,
- Tereza Maria Pereira Fontes,
- Silvia Espiridião,
- Luiz Kulay Júnior
Views109See morePURPOSE: 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.
Views109This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Summary
Artigos OriginaisMorphological and physiological analysis of livers and kidneys of pregnant rats and their fetuses treated by the association of zidovudine, lamivudine and ritonavir for the whole period of pregnancy
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(11):556-562
01-20-2010DOI 10.1590/S0100-72032010001100007
- Adriana Wagner,
- Adelino Moreira de Carvalho,
- Mary Uchiyama Nakamura,
- Ricardo Santos Simões,
- Tereza Maria Pereira Fontes,
- Silvia Espiridião,
- Luiz Kulay Júnior
Views109See morePURPOSE: 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.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -
Artigos Originais
Morphological analysis of liver and kidneys of pregnant rats and their fetuses upon chronic Ritonavir administration
- Adelino Moreira de Carvalho,
- Ricardo Santos Simões,
- Fábio Hideo Martins Oliveira,
- Manuel de Jesus Simões,
- Ricardo Martins Oliveira-Filho, [ ... ],
- Luiz Kulay Júnior
10-29-2007
Summary
Artigos OriginaisMorphological analysis of liver and kidneys of pregnant rats and their fetuses upon chronic Ritonavir administration
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):346-351
10-29-2007DOI 10.1590/S0100-72032007000700004
- Adelino Moreira de Carvalho,
- Ricardo Santos Simões,
- Fábio Hideo Martins Oliveira,
- Manuel de Jesus Simões,
- Ricardo Martins Oliveira-Filho,
- Mary Uchiyama Nakamura,
- Luiz Kulay Júnior
Views117See morePURPOSE: 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.
Views117This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Summary
Artigos OriginaisMorphological analysis of liver and kidneys of pregnant rats and their fetuses upon chronic Ritonavir administration
Revista Brasileira de Ginecologia e Obstetrícia. 2007;29(7):346-351
10-29-2007DOI 10.1590/S0100-72032007000700004
- Adelino Moreira de Carvalho,
- Ricardo Santos Simões,
- Fábio Hideo Martins Oliveira,
- Manuel de Jesus Simões,
- Ricardo Martins Oliveira-Filho,
- Mary Uchiyama Nakamura,
- Luiz Kulay Júnior
Views117See morePURPOSE: 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.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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