title: Altered distribution and toxicity of digitoxigenin in fasted mice.
abstract: 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.
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004073:Digitoxigenin / Q000378:metabolism / Q000633:toxicity*; D005215:Fasting; D007928:Lethal Dose 50; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced; D012701:Serotonin / Q000378:metabolism; D014018:Tissue Distribution; D014364:Tryptophan / Q000494:pharmacology
chemical_list: D004073:Digitoxigenin; D012701:Serotonin; D014364:Tryptophan