[14C]monocrotaline kinetics and metabolism in the rat

J. E. Estep, M. W. Lame, D. Morin, A. D. Jones, Dennis W Wilson, H. J. Segall

Research output: Contribution to journalArticle

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Abstract

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 μCi/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 μCi/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.

Original languageEnglish (US)
Pages (from-to)135-139
Number of pages5
JournalDrug Metabolism and Disposition
Volume19
Issue number1
StatePublished - 1991

Fingerprint

Monocrotaline
Enzyme kinetics
Metabolism
Rats
Liver
Tissue
Radioactivity
Blood
Lung
Erythrocytes
Tissue Distribution
Kidney
Plasmas
Pyrrolizidine Alkaloids
Metabolites
Pulmonary Hypertension
Bile
Toxicity
Proteins
Necrosis

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Estep, J. E., Lame, M. W., Morin, D., Jones, A. D., Wilson, D. W., & Segall, H. J. (1991). [14C]monocrotaline kinetics and metabolism in the rat. Drug Metabolism and Disposition, 19(1), 135-139.

[14C]monocrotaline kinetics and metabolism in the rat. / Estep, J. E.; Lame, M. W.; Morin, D.; Jones, A. D.; Wilson, Dennis W; Segall, H. J.

In: Drug Metabolism and Disposition, Vol. 19, No. 1, 1991, p. 135-139.

Research output: Contribution to journalArticle

Estep, JE, Lame, MW, Morin, D, Jones, AD, Wilson, DW & Segall, HJ 1991, '[14C]monocrotaline kinetics and metabolism in the rat', Drug Metabolism and Disposition, vol. 19, no. 1, pp. 135-139.
Estep JE, Lame MW, Morin D, Jones AD, Wilson DW, Segall HJ. [14C]monocrotaline kinetics and metabolism in the rat. Drug Metabolism and Disposition. 1991;19(1):135-139.
Estep, J. E. ; Lame, M. W. ; Morin, D. ; Jones, A. D. ; Wilson, Dennis W ; Segall, H. J. / [14C]monocrotaline kinetics and metabolism in the rat. In: Drug Metabolism and Disposition. 1991 ; Vol. 19, No. 1. pp. 135-139.
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