<i>In situ</i>intestinal absorption of 2-chloro-<i>N</i>-isopropylacetanilide (propachlor) and non-biliary excretion of metabolites into the intestinal tract of rats, pigs and chickens

Struble, Craig B

doi:10.3109/00498259109039453

Cited by 9 publications

(2 citation statements)

References 18 publications

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“…It is possible that a large part of the BPA residues recovered in feces and digestive tracts had actually been directly secreted by the intestine. Such a mechanism has already been demonstrated for other xenobiotics (47,48). It cannot be ruled out that the enterohepatic cycling kinetics of BPA may have been modified by the fact that the animals had not been fed during the experiment.…”

Section: Discussionmentioning

confidence: 75%

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Zalko¹,

Soto²,

Dolo³

et al. 2003

Environ Health Perspect

174

118

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We investigated the metabolic fate of a low dose (25 micro g/kg) of bisphenol A [2,2-bis(4-hydroxy-phenyl)propane] (BPA) injected subcutaneously in CD1 pregnant mice using a tritium-labeled molecule. Analytic methods were developed to allow a radio-chromatographic profiling of BPA residues in excreta and tissues, as well as in mothers' reproductive tracts and fetuses, that contained more than 4% of the administered radioactivity. BPA was extensively metabolized by CD1 mice. Identified metabolite structures included the glucuronic acid conjugate of BPA, several double conjugates, and conjugated methoxylated compounds, demonstrating the formation of potentially reactive intermediates. Fetal radioactivity was associated with unchanged BPA, BPA glucuronide, and a disaccharide conjugate. The latter structure, as well as that of a dehydrated glucuronide conjugate of BPA (a major metabolite isolated from the digestive tract), showed that BPA metabolic routes were far more complex than previously thought. The estrogenicity of the metabolites that were identified but not tested for hormonal activity cannot be ruled out; however, in general, conjugated BPA metabolites have significantly lower potency than that of the parent compound. Thus, these data suggest the parental compound is responsible for the estrogenic effects observed in fetuses exposed to BPA during gestation in this mammalian model.

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Section: Discussionmentioning

confidence: 75%

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Zalko¹,

Soto²,

Dolo³

et al. 2003

Environ Health Perspect

174

118

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“…When a drug is administered parenterally, the route by which it is distributed to the large intestine is thought to be biliary and intestinal excretion. Recently, intestinal excretion has become a well-recognized phenomenon (3,4,7,13,22). However, little is known about the pharmacokinetics of injectable drugs for swine dysentery in relation to efficacy.…”

mentioning

confidence: 99%

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice

Hayashi

Okada

Kondo

et al. 1991

Antimicrob Agents Chemother

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The therapeutic effects of subcutaneously administered sedecamycin on experimental Treponema hyodysenteriae infection in mice were evaluated. Sedecamycin was more active than tiamulin and lincomycin. The efficacy of sedecamycin upon subcutaneous administration was similar to that upon oral administration. Sedecamycin given subcutaneously provided similar degrees of protection in bile duct-ligated and intact mice. Pharmacokinetic studies utilizing a liquid chromatographic technique were carried out to determine the concentration of sedecamycin in the cecum, the site of T. hyodysenteriae infection in mice. Little sedecamycin was found; however, lankacidinol, a major metabolite of sedecamycin, was found in the cecal contents of intact mice after subcutaneous or oral administration of sedecamycin. Lankacidinol was also found in the cecal contents of bile duct-ligated mice, although the concentration found after subcutaneous administration of sedecamycin was much lower than that found after subcutaneous or oral administration to intact mice. These results indicate that sedecamycin is excreted directly into the intestinal tract as an active metabolite by a route other than the bile duct. It is suggested that this intestinal excretion plays an important role in the efficacy of subcutaneously administered sedecamycin against cecal infection of mice by T. hyodysenteriae.Treponema hyodysenteriae, the etiologic agent of swine dysentery, is characterized by mucohemorragic diarrhea (9,25). In general, severely infected animals are reluctant to consume the medicated feed. In such cases, parenteral administration of effective drugs, lincomycin (8) and tiamulin (1, 2), is used for treatment. Swine dysentery is infection with T. hyodysenteriae in the large intestine (5, 10); therefore, a sufficient amount of a drug must be distributed to the large intestine. When a drug is administered parenterally, the route by which it is distributed to the large intestine is thought to be biliary and intestinal excretion. Recently, intestinal excretion has become a well-recognized phenomenon (3,4,7,13,22). However, little is known about the pharmacokinetics of injectable drugs for swine dysentery in relation to efficacy.Experimental infection of mice and rabbits with T. hyodysenteriae had failed until Joens and Glock (14) reported that CF1 mice inoculated with T. hyodysenteriae for 2 consecutive days after a 72 h of fasting developed cecal and colonic lesions. Later, Suenaga and Yamazaki (24) reported that they examined mouse strains and found that Ta:CF#1 mice developed gross cecal lesions after a single oral administration of T. hyodysenteriae without fasting. By using this animal model, we have shown that orally administered sedecamycin, a 17-member macrocyclic antibiotic ( Fig. 1), shows good efficacy in mice (11).The objective of this study was to evaluate the efficacy of subcutaneous administration of sedecamycin against experimental infection of mice with T. hyodysenteriae and to explain the mechanisms of the efficacy by the concentra...

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Absorption, Enterohepatic Circulation, and Fecal Excretion of Toxicants

Watkins

2010

Comprehensive Toxicology

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In situintestinal absorption of 2-chloro-N-isopropylacetanilide (propachlor) and non-biliary excretion of metabolites into the intestinal tract of rats, pigs and chickens

Cited by 9 publications

References 18 publications

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Biotransformations of bisphenol A in a mammalian model: answers and new questions raised by low-dose metabolic fate studies in pregnant CD1 mice.

Role of intestinal excretion in the effect of subcutaneously administered sedecamycin on cecal infection caused by Treponema hyodysenteriae in mice

Absorption, Enterohepatic Circulation, and Fecal Excretion of Toxicants

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