Elimination and metabolism of permethrin isomers in rainbow trout.
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Biomedical subjects
Publications and source records attributed to D E Rickert.
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A correlation of myelotoxic effect with concentration or a foreign compound of its metabolite at the site of action may provide useful insights into the mechanism of toxic action and/or its amelioration. This correlation requires sensitive and specific assay methods. This communication describes useful methods for the study of benzene disposition in rodents. The assays are sensitive, specific, and rapid. They rely on gas chromatography-mass spectrometry and on high performance liquid chromatography. These methods have allowed measurement of catechol, phenol, and hydroquinone in samples of rodent bone marrow following inhalation exposure to benzene. Their application to the study of benzene metabolism in rat bone marrow in situ is also described.
The incidence of hepatocellular carcinoma is higher in male rats fed 35 mg of dinitrotoluene (DNT) per kg than in female rats fed the same dose. Sex differences in DNT disposition and/or metabolism may account for this difference. This study characterized the metabolism and biliary excretion of 2,4-DNT in male and female isolated perfused rat livers. Livers from both sexes displayed a capacity for oxidation, reduction, acetylation and conjugation of 2,4-DNT (or its metabolites). Oxidation of 2,4-DNT to 2,4-dinitrobenzyl alcohol followed by glucuronidation to 2,4-dinitrobenzyl alcohol glucuronide (DNBalcG) was the major route of 2,4-DNT metabolism in both sexes. Formation of DNBalcG accounted for 10 to 30% of the total initial 2,4-DNT concentration in perfusates. After perfusion with 20 microM 2,4-DNT, male livers excreted larger quantities of DNBalcG in the bile (392 nmol) than female livers (172 nmol); at the same 2,4-DNT concentration, perfusates from female livers contained over 3 times as much DNBalcG as male perfusates. These data suggested that female livers transported DNBalcG into the bile at slower rates than male livers. The transport of DNBalcG into the bile of male, but not female, livers appeared to be saturated after perfusion with 20 micro M 2,4-DNT. No sex differences in the hepatic macromolecular covalent binding were observed after perfusion of livers with either 20 or 70 micro M 2,4-DNT. These data suggest that the major difference in the in vitro metabolism of 2,4-DNT between male and female rats is the larger quantities of DNBalcG excreted in the bile of male rats than female rats.
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Polybrominated biphenyls (PBBs) stimulate hepatic drug metabolism in adult and developing rats. The purpose of this investigation was to determine the influence of PBBs on the development of the liver as an organ for chemical excretion. Exposure of developing rats to polybrominated biphenyls (PBBs) by feeding 50 ppm of PBBs to pregnant or lactating mothers and rat weanlings did not produce overt toxicity when compared to controls over a 49-day postnatal period. However, prenatal and postnatal dietary exposure to PBBs resulted in elevated liver weight. In 15-day-old rats, increased liver weight after PBBs was correlated with enhanced ouabain transport from plasma into bile. Liver weight was also elevated in 21-, 35- and 49-day-old rats treated with PBBs, but this effect was not associated with stimulation of ouabain transport in these animals. Stimulation of ouabain transport after PBBs in 15-day-old rats was associated with increased hepatic uptake of ouabain. Stimulation in 15-day-old rats and not older rats may be attributed to the relative importance of uptake for ouabain transport in 15-day-old rats.
Synthesis of prostaglandin E2 by renal medulla from SHR and WKY rats was compared during early postnatal development. Although arterial blood pressure was significantly higher in SHR as early as 6 weeks of age, no difference in renal medullary prostaglandin synthesis was observed.
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Female rats were fed PBBs in the diet (50 ppm) from day 8 of gestation to day 21 of gestation, from day 1 postpartum to day 14 postpartum or from day 8 of gestation through day 14 postpartum. Levels of PBBs were measured in various tissues. Small concentrations of PBBs (less than 5 microgram/g) were found in the brain, heart, lung, liver, small intestine, placenta, and gravid uterus. Larger concentrations (less than 30 microgram/g) were found in kidneys, the nongravid uterus, skin, mammary tissue, and fat. Lactation did not significantly alter the concentrations of PBBs found in tissues other than mammary tissue. Offspring were subjected to several exposure regimens by cross-fostering. Concentrations of PBBs in the neonatal livers were higher than in the adults nursing them. Transfer of PBBs via the milk appears to be much more important to appearance of PBBs in newborns than does placental transfer.
1. The absorption and glucuronylation of [14C]diethylstilbestrol (DES) were studied in situ in segments of rat small intestine. 2. DES glucuronide accounted for nearly 50% of the methanol-soluble radioactive material appearing in the intestinal venous blood. 3. There was no difference between DES glucuronide formation in intestinal segments near the pyloric sphincter and in segments located near the ileo-caecal junction. 4. The appearance of DES and its glucuronide in the venous blood of aborally-located segments was dose-dependent from 0.1 to 5 mM, but in orally-located segments, an increase in DES concn. from 2 to 5 mM produced no increase in DES or its glucuronide in the venous blood. In neither of these intestinal regions was the rate of appearance of DES or DES glucuronide dependent upon intestinal blood flow. 5. The results indicate that intestinal glucuronylation of certain compounds during absorption may be significant over a wide range of concn. in all regions of the intestine.
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