Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, the effects of chloroquine and ethanol administration during gestation have been investigated on the developing rat fetus. Intragastric administration of chloroquine (700 mg/kg body weight) resulted in several structural abnormalities. The incidence of hepatomegaly was increased by 30%, the liquification of visceral organs was increased by 15% and a 9% higher incidence of cleft palate, wrist drop, clubbed foot and brain liquification was observed in the fetuses from the chloroquine-treated group compared to the corresponding controls. Fetuses from the chloroquine-treated group also showed a decrease of about 40% in the body weight and a 30% reduction in the ossification of the sternum. The teratogenic effects of oral ethanol administration in several respects were similar to those of the chloroquine. Ethanol, when administered as 30% of the total daily calories, resulted in growth retardation, resorption, still births, liquification of the brain, wrist drop and clubbed foot. Additionally, ethanol resulted in the inhibition of several metabolic pathways in the liver and brain of the developing fetuses. This included the inhibition of protein, RNA and DNA metabolism in the fetal livers and brains. The feto-toxic effects of these two xenobiotics and their possible molecular mechanisms have been discussed.
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PMID:Toxicological consequences of chloroquine and ethanol on the developing fetus. 262 56

The organic phase of a leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD). The teratogenic potential of OPL was determined in two inbred and one hybrid mouse strain which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was orally administered in corn oil on Days 6-15 of gestation to C57BL/6J mice (Ahb/Ahb) at doses of 0, 0.1, 0.3, 0.5, and 0.7 g kg-1 day-1 and to DBA/2J (Ahd/Ahd) females, which were mated with either DBA/2J or C57BL/6J males, at 0, 0.5, 1, and 2.0 g kg-1 day-1. In C57BL/6J mice, which express a high-affinity Ah receptor that avidly binds TCDD, the ED50's of OPL for cleft palate and hydronephrosis were 0.44 and 0.11 g OPL kg-1 day-1, respectively. Maternal mortality was 5% at the highest dose. In DBA/2J fetuses, which express a low-affinity receptor, neither treatment-related cleft palate nor hydronephrosis was induced by dose levels that caused 36% maternal mortality. In hybrid D2B6F1 fetuses, the incidence of cleft palate reached only 8% at 2 g OPL kg-1 day-1 but the ED50 for hydronephrosis was 0.76 g OPL kg-1 day-1. TCDD was similarly administered to pregnant C57BL/6J mice at 0, 0.5, 1, 2, and 4 micrograms kg-1 day-1 and to DBA/2J mice at 0, 0.5, 2, 4, and 8 micrograms kg-1 day-1. In C57BL/6J fetuses, the ED50's for cleft palate and hydronephrosis were 4.6 and 0.73 microgram TCDD kg-1 day-1, respectively. In DBA/2J fetuses the ED50's for cleft palate and hydronephrosis were 15.0 and 6.4 micrograms TCDD kg-1 day-1, respectively. Both the OPL and TCDD caused maternal hepatomegaly and thymic atrophy in all strains, but increased only C57BL/6J fetal weights. OPL decreased the number of fetuses per C57BL/6J dam at the two highest doses but there were no other reproductive effects in any of the groups. It was concluded that the OPL is teratogenic and that hydronephrosis is a sensitive measure of TCDD toxicity in a complex organic mixture. Based on the ED50's of OPL- and TCDD-induced cleft palate and hydronephrosis in the C57BL/6J strain, the OPL had TCDD equivalence of 6.6 and 10.5 ppm, respectively. These values compare closely with the chemical analysis of 3 ppm.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Teratology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the love canal. 276 49

Prolonged administration of either lithium (7 mg/kg body wt.) or ethanol (30% of daily caloric intake) for 10 days to pregnant rats results in several anatomical abnormalities in the fetus. Intragastric administration of lithium carbonate to pregnant rats immediately after confirmation of pregnancy resulted in high incidence of cleft palate, growth retardation, brain liquification and pulpy brain, hepatomegaly and digital abnormalities, when compared to the saline-treated controls. Furthermore, lithium administration during gestation also resulted in other less frequently observed abnormalities in the fetus, e.g., cardiomegaly, hydronephrosis, ankle-joint defects, syndactyly, defected ribs and sternum ossification defects. Chronic ethanol consumption by pregnant rats during early gestation also resulted in several anatomical abnormalities of prenatal growth retardation, resorption and still births, cleft palate, hydrocephaly and hydronephrosis. The severity and frequency of several of the fetal abnormalities were compounded when lithium and ethanol were administered simultaneously. The possible mechanisms of lithium and ethanol teratogenicity and their synergistic effects have been explained on a biochemical basis.
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PMID:Teratogenic effects of lithium and ethanol in the developing fetus. 308 78

A male infant presenting with multiple anomalies including a midline cleft palate, anasarca, hepatomegaly, pulmonary edema, agenesis of the corpus collosum, and complex congential cardiac anomalies was found to have mosaicism for an additional chromosome that appeared (following GTG-banding and FISH) to be a monocentric isochromosome of the short arm of chromosome 8 (46,XY/47,XY, +i(8p)). Nine other cases of mosaicism for an additional i(8p) were reviewed. Considerable phenotypic variation was noted. Consistent features were identified including agenesis of the corpus callosum, cardiac malformations, and minor facial dysmorphology. The phenotype of these patients partially overlaps those of trisomy 8 and trisomy 8p. By studying additional individuals with this condition, mosaic tetrasomy 8p may emerge as a recognizable clinical phenotype.
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PMID:Mosaic "tetrasomy" 8p: case report and review of the literature. 859 71

The Ah receptor (AHR) mediates the metabolic adaptation to a number of planar aromatic chemicals. Essential steps in this adaptive mechanism include AHR binding of ligand in the cytosol, translocation of the receptor to the nucleus, dimerization with the Ah receptor nuclear translocator, and binding of this heterodimeric transcription factor to dioxin-responsive elements (DREs) upstream of promoters that regulate the expression of genes involved in xenobiotic metabolism. The AHR is also involved in other aspects of mammalian biology, such as the toxicity of molecules like 2,3,7,8-tetrachlorodibenzo-p-dioxin as well as regulation of normal liver development. In an effort to test whether these additional AHR-mediated processes require a nuclear event, such as DRE binding, we used homologous recombination to generate mice with a mutation in the AHR nuclear localization/DRE binding domain. These Ahr(nls) mice were found to be resistant to all 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxic responses that we examined, including hepatomegaly, thymic involution, and cleft palate formation. Moreover, aberrations in liver development observed in these mice were identical to that observed in mice harboring a null allele at the Ahr locus. Taken in sum, these data support a model where most, if not all, of AHR-regulated biology requires nuclear localization.
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PMID:Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor. 1262 Oct 46

The protective effect of geranylgeranylacetone (GGA), an antiulcer drug, against the acute toxicity and teratogenicity produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in C57BL/6J mice. When mice were co-treated, GGA reduced the loss of body weight gain and lethality produced by TCDD but hepatomegaly and thymic atrophy were not improved. Additionally, no protective effect of GGA was observed in the formation of cleft palate and hydronephrosis in mouse fetuses caused by maternal exposure to TCDD. To clarify the reducing mechanism by GGA, the Hsp70.1 mRNA levels in liver and intestine were analyzed. However, it was difficult to explain the effect of GGA from the induction of Hsp70.1. GGA had also no effect on the induction of hepatic ethoxyresorufin O-deethylase activity by TCDD. These data suggest that GGA exhibits a protective effect against some forms of dioxin toxicity by a mechanism without involving inhibition of arylhydrocarbon receptor activation.
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PMID:Reduction of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice using an antiulcer drug, geranylgeranylacetone. 1534 Feb 26