Altered distribution and toxicity of digitoxigenin in fasted mice

• Published in: Life sciences (1973) Vol. 37; no. 8; p. 775
• Main Authors: Warwick, R O, Smith, M P, Graffy, M A, Lage, G L
• Format: Journal Article
• Language: English
• Published: Netherlands 26-08-1985
• Subjects: Animals; Body Weight - drug effects; Digitoxigenin - metabolism; Digitoxigenin - toxicity; Fasting; Lethal Dose 50; Liver - metabolism; Male; Mice; Organ Size - drug effects; Seizures - chemically induced; Serotonin - metabolism; Tissue Distribution; Tryptophan - pharmacology
• ISSN: 0024-3205
• DOI: 10.1016/0024-3205(85)90548-X

Intravenous administration of digitoxigenin (DTXGN) evokes seizure episodes in mice which may be dependent on brain biogenic amines such as serotonin (5-HT). Fasting is known to have effects on both drug toxicity and brain 5-HT synthesis. The purpose of this study was to assess the effects of overnight fasting on DTXGN toxicity. The i.v. LD-50 of DTXGN was increased by 61% in fasted mice. Adjustment of DTXGN dose for the decrease in body weight of fasted mice did not alter the fasting induced protection. A loading dose of 1-tryptophan (25 mg/kg, i.p.) did not alter mortality rates in either fed or fasted mice. Cortical levels of 3H-DTXGN were decreased significantly by 25% in fasted mice. Liver and blood levels were elevated significantly. These data suggest that decreased DTXGN toxicity is associated with a decrease in its distribution to the cerebral cortex and emphasize the importance of acute dietary status in the expression of drug toxicity.