DMD Simcyp

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Estep, J. E.
Right arrow Articles by Segall, H. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Estep, J. E.
Right arrow Articles by Segall, H. J.

[14C]monocrotaline kinetics and metabolism in the rat

JE Estep, MW Lame, D Morin, AD Jones, DW Wilson and HJ Segall

Dept of Veterinary Pharmacology and Toxicology, University of California, Davis 95616.

The pyrrolizidine alkaloid monocrotaline (MCT) has been shown to cause hepatic necrosis and pulmonary hypertension in the rat. To better understand the mechanism of action, tissue distribution and covalent binding studies were conducted at 4 and 24 hr following administration of [14C]MCT (60 mg/kg, 200 microCi/kg, sc). For the 4 hr study, the levels of MCT equivalents were 85, 74, 67, 36, and 8 nmol/g of tissue for red blood cells (RBC), liver, kidney, lung, and plasma, respectively, while the covalent binding levels were 125, 132, 39, 64, 44 pmol/mg of protein for tissues as listed above. The 24-hr tissue distribution levels were 49, 25, 9, 10, 2 nmol/g of tissue for RBC, liver, kidney, lung, and plasma, respectively, while covalent binding was 74, 28, and 55 pmol/mg of protein for liver, kidney, and lung, respectively. We also studied the kinetics of [14C]MCT (60 mg/kg, 10 microCi/kg, iv), which demonstrated rapid elimination of radioactivity with approximately 90% recovery of the injected radioactivity in the urine and bile by 7 hr. The plasma levels of radioactivity dropped from 113 nmol/g of MCT equivalents to 11 nmol/g at 7 hr while RBC levels decreased from 144 to only 81 nmol/g at the same time point. The apparent retention of MCT equivalents in the RBC suggests that this organ may act as the carrier of metabolites from the liver to other organs including the lung and may play a role in the pulmonary toxicity.

Volume 19, Issue 1, pp. 135-139, 01/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Laudi, S. Trump, V. Schmitz, J. West, I. F. McMurtry, H. Mutlak, U. Christians, J. Weimann, U. Kaisers, and W. Steudel
Serotonin transporter protein in pulmonary hypertensive rats treated with atorvastatin
Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L630 - L638.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
F. Akhavein, E. J. St.-Michel, E. Seifert, and C. V. Rohlicek
Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats
J Appl Physiol, July 1, 2007; 103(1): 287 - 295.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
L. D. DeLeve, Y. Ito, N. W. Bethea, M. K. McCuskey, X. Wang, and R. S. McCuskey
Embolization by sinusoidal lining cells obstructs the microcirculation in rat sinusoidal obstruction syndrome
Am J Physiol Gastrointest Liver Physiol, June 1, 2003; 284(6): G1045 - G1052.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.