Metabolism of L-(guanidinooxy-/sup 14/C)canavanine in the rat

Journal Article · Tue Dec 01 00:00:00 EST 1987 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(87)90062-7· OSTI ID:5411856

Thomas, D A; Rosenthal, G A

The metabolism of L-canavanine, a nonprotein amino acid with significant antitumor effects, was investigated. L-Canavanine, provided at 2.0 g/kg, was supplemented with 5 microCi of L-(guanidinooxy-/sup 14/C)canavanine (58 microCi/mumol) and administered iv, sc, or orally to female Sprague-Dawley rats weighing approximately 200 g. /sup 14/C recovery in the urine at 24 hr was 83, 68, or 61%, respectively, of the administered dose. Another 5-8% of the /sup 14/C was expired as /sup 14/CO/sub 2/. The gastrointestinal tract contained 21% of orally administered /sup 14/C. Serum, feces, tissues, and de novo synthesized proteins only accounted for a few percent of the original dose by any administrative route. Analysis of the /sup 14/C-containing urinary metabolites revealed that (/sup 14/C) urea accounted for 88% of the urinary radioactivity for an iv injection, 75% for sc administration, and 50% following an oral dose. By all routes of administration, (/sup 14/C)guanidine represented 5% of the radioactivity in the urine and (/sup 14/C)guanidinoacetic acid accounted for 2%. Serum and urine amino acid analysis showed a markedly elevated ornithine level. Basic amino acids such as histidine, lysine, and arginine were also higher in the urine. Plasma ammonia levels were determined following oral canavanine doses of 1.0, 2.0, and 4.0 g/kg. A rapid but transient elevation in plasma ammonia was observed only at the 4.0 g/kg dose. This indicates that elevated plasma ammonia is not a likely cause of canavanine toxicity at the drug concentrations used in this study.

• Research Organization: Univ. of Kentucky, Lexington
• OSTI ID: 5411856
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Vol. 91:3
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GUANIDINES
METABOLISM
AMINO ACIDS
AMMONIA
CARBON 14 COMPOUNDS
METABOLITES
ORAL ADMINISTRATION
RATS
TRACER TECHNIQUES
ANIMALS
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
HYDRIDES
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NITROGEN COMPOUNDS
NITROGEN HYDRIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
RODENTS
VERTEBRATES
550501* - Metabolism- Tracer Techniques