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Biomedical subjects

L R Curtis

Publications and source records attributed to L R Curtis.

51 records · Page 3Linked to original sources
PubMed1984

Impaired biliary excretion of taurocholate associated with increased biliary tree permeability in mirex- or chlordecone-pretreated rats.

Impaired biliary excretion of exogenously provided xenobiotic metabolites was demonstrated previously after pre-exposure of rats to mirex (MX) or chlordecone (CD). This toxicity was studied further in pentobarbital-anesthetized rats, cannulated at the common bile duct. We found reduced biliary excretion rates for exogenous [14C]taurocholic acid (3 or 10 mumol/kg bolus) after 15-day dietary pretreatment of male rats with 20 or 100 ppm of MX or CD. Hepatobiliary dysfunction was dose-dependent. Maximal reduction in excretory rate on a per gram of liver basis (50%) followed treatment with 100 ppm of MX. Biliary tree permeability was estimated to ascertain whether efflux of canalicular bile into the hepatic circulation explained hepatobiliary dysfunction. Bile-to-plasma concentration ratios for [3H]sucrose increased in parallel with MX- and CD-impaired biliary excretion. Modeling the relationship between bile flow and bile-to-plasma [3H]sucrose ratio indicated the site of increased permeability involved a paracellular pathway. Bile flow (on a per gram of liver basis) and biliary clearance of [14C]erythritol were both reduced by 100 ppm of these toxicants. The above effects occurred in the absence of substantial hepatocellular necrosis, whereas liver enlargement increased in a dose-dependent manner. Maximal liver enlargement (doubling of liver weight) resulted from 100 ppm of MX treatment. These results indicated that hepatobiliary dysfunction induced by MX and CD was at least partially explained by increased permeability of the biliary tree.

Animals↗
PubMed1983

Glucuronidation and biliary excretion of phenolphthalein in temperature-acclimated steelhead trout (Salmo gairdneri).

Conjugative metabolism and biliary excretion of phenolphthalein (PP) were studied in steelhead trout (Salmo gairdneri) acclimated to 10, 14 or 18 degrees C. Significant seasonal effects were found on liver weight to body weight ratio and conjugative metabolism but not biliary excretion of free plus conjugate of PP. Temperature did not significantly interact with these relationships. PP was excreted in bile as parent compound and the glucuronide conjugate at all temperatures. Saturation of the excretory process was apparent at a dose of approximately 10 mumol/kg (i.p.) at 10 and 14, but not 18 degrees C.

Acclimatization↗
PubMedDate not supplied

Low dose chlordecone pretreatment altered cholesterol disposition without induction of cytochrome P-450.

Pretreatment of mice with low doses of chlordecone (CD) alters the pattern of distribution of a subsequent tracer dose of [14C]CD. We call this preexposure effect a pretreatment disposition response (PDR) and suggest that it reflects important cellular responses to lipophilic compounds. The present study examined three possible mechanisms for CD-induced PDR (CD-PDR). The first was that CD-PDR occurred with induction of the cytochrome P-450 system. A cumulative dose of 45 mg/kg CD caused a PDR, increased the content of cytochrome P-450, and elevated the activities of ethoxyresorufin- and ethoxycoumarin-O-deethylases (EROD and ECOD). A cumulative dose of 10 mg/kg caused a PDR, but did not affect cytochrome P-450, EROD, or ECOD, indicating that an induction of the cytochrome P-450 system in not necessary for PDR. A second possibility examined was that CD-PDR resulted because of an altered affinity of a subcellular fraction. Following a pretreatment regimen designed to produce PDR, amounts of [14C]CD in each fraction paralleled homogenate values in the liver and the kidney. However, when values were calculated as percentages of total label recovered, it was apparent that [14C]CD levels were higher in the microsomal fraction of the liver. Finally, the possibility that CD-PDR occurred because of an interaction of CD with proteins involved in cholesterol synthesis and transport was addressed. CD pretreatment increased disposition of a dose of [14C]cholesterol to the fat at the expense of [14C]cholesterol in the liver and kidney.

Animals↗
PubMedDate not supplied

A characterization of chlordecone pretreatment-altered pharmacokinetics in mice.

Lipophilic chlorinated hydrocarbons pose a potential health hazard to humans and animals and the toxicity of a number of these compounds has been well documented. Despite the low environmental concentrations of most of these chemicals, much of the research conducted to date has used maximally tolerated doses. Our research, conducted with low, apparently nontoxic, doses of the insecticide chlordecone (CD), showed that the administration of CD (5 mg/kg ip) to mice (C57BL/6N and DBA/2N strains) caused a time-dependent alteration in the pattern of distribution of a subsequently administered dose of [14C]CD. Livers of CD-pretreated animals contained less label than did those from controls and CD pretreatment increased amounts of label in kidney, lung, fat, and muscle. Changes did not appear to be due to an altered rate of metaboLism and analysis of total CD in tissues (unlabeled plus [14C]CD) indicated that these responses were not due to a simple redistribution phenomenon. We have termed this preexposure effect a pretreatment disposition response (PDR) and feel it may reflect an important cellular response to lipophilic compounds. CD-induced PDR is dose related, exhibits a threshold, and is saturable at a given level of induction. In addition, PDR exhibits some specificity, inasmuch as pretreating mice with CD (5 mg/kg) does not alter the distribution of subsequently administered [14C]dieldrin. The characteristics of threshold, saturability, and specificity are consistent with the premise that CD-induced PDR is a protein-mediated phenomenon.

Animals↗