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Mechanisms and pathology of monocrotaline pulmonary toxicity.
Experimental evidence supporting hypotheses that MCT is activated to a reactive metabolite in the liver and is then transported by red blood cells to the lung, where it initiates endothelial injury is presented. Expand
Long-term kinetic study of beta-carotene, using accelerator mass spectrometry in an adult volunteer.
- S. Dueker, Y. Lin, +5 authors A. Clifford
- Chemistry, Medicine
- Journal of lipid research
- 1 November 2000
AMS is an excellent tool for defining the in vivo metabolic behavior of beta-carotene and related compounds at physiological concentrations and the data suggest that retinyl esters derived from beta- carotene may undergo hepatic resecretion with VLDL in a process similar to that observed for beta- Carotene. Expand
Progressive inflammatory and structural changes in the pulmonary vasculature of monocrotaline-treated rats.
It is concluded that adventitial inflammation precedes morphologic evidence of medial changes in monocrotaline-induced pulmonary hypertension, involvement of intraacinar arteries precedes that of major bronchus associated arteries, and both pulmonary arteries and veins are involved in monOCrotaline -induced pulmonary vascular disease in the rat. Expand
Formation of cyclic adducts of deoxyguanosine with the aldehydes trans-4-hydroxy-2-hexenal and trans-4-hydroxy-2-nonenal in vitro.
T-4HH and t-4HN possess the ability to alkylate deoxyguanosine in vitro and suggest possible mechanisms for 4-hydroxyalkenal and pyrrolizidine alkaloid genotoxicity. Expand
DNA cross-linking in mammalian cells by pyrrolizidine alkaloids: structure-activity relationships.
- J. Hincks, H. Kim, H. Segall, R. Molyneux, F. Stermitz, R. Coulombe
- Biology, Medicine
- Toxicology and applied pharmacology
- 1 October 1991
Although the PAs induced DNA cross-linking to varying degrees, cell viabilities for all treatment groups were greater than 90% as determined by trypan blue dye exclusion, and two structural determinants of biological activity appear to be the presence of both a macrocyclic necic acid ester and an alpha,beta-unsaturated ester function. Expand
Monocrotaline pyrrole targets proteins with and without cysteine residues in the cytosol and membranes of human pulmonary artery endothelial cells
It is suggested that molecular events underlying MCTP toxicity are initiated at the plasma membrane or readily accessible subcellular regions including the cytosol and membranes of the endoplasmic reticulum and mitochondria. Expand
Genotoxicity and cytotoxicity of selected pyrrolizidine alkaloids, a possible alkenal metabolite of the alkaloids, and related alkenals.
Genotoxicity and cytotoxicity results would predict a carcinogenic role for both the PAs and the alkenals, lending support to the proposed role of trans-4-OH-2-hexenal as an important toxic metabolite of the P as. Expand
Involvement of cytochrome P450 3A in the metabolism and covalent binding of 14C‐monocrotaline in rat liver microsomes
- M. J. Reid, M. Lamé, D. Morin, D. Wilson, H. Segall
- Chemistry, Medicine
- Journal of biochemical and molecular toxicology
The metabolism and covalent binding of 14C‐monocrotaline in Sprague–Dawley (SD) rat liver microsomes was investigated using the inducers dexamethasone, clotrimazole, pregnenolone‐16α‐carbonitrile,… Expand
N-acetylcysteine-conjugated pyrrole identified in rat urine following administration of two pyrrolizidine alkaloids, monocrotaline and senecionine.
This report demonstrates that an Ehrlich-reagent-positive metabolite of monocrotaline and senecionine is excreted in the urine of male rats as an N-acetylcysteine conjugate of… Expand
Protein Targets of Monocrotaline Pyrrole in Pulmonary Artery Endothelial Cells*
- M. Lamé, A. D. Jones, D. Wilson, S. Dunston, H. Segall
- Medicine, Chemistry
- The Journal of Biological Chemistry
- 15 September 2000
Specific endothelial targets for 14C-monocrotaline pyrrole are determined using two-dimensional gel electrophoresis and autoradiographic detection of protein metabolite adducts using matrix-assisted laser desorption ionization mass spectrometry and sequence data bases. Expand