The efficacy of diazepam in the treatment of acute iron overload in rats

Frank F. Fassos, Matitiahu Berkovitch, Nicholas Daneman, Lee Koren, Ross Cameron, Julia Klein, Corrado Falcitelli, Patrick St. Louis, Richard Daneman, Gideon Koren*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

While conducting studies on the prevention of mortality from acute iron intoxication in rats, diazepam, given to prevent animal suffering, was observed to be associated with reduced mortality in a limited number of animals. The objective was to assess whether diazepam reduces mortality following acute iron intoxication in rats. Survival of rats was compared among groups receiving (i) orally 612 mg/kg iron alone (LD60), (ii) iron with a subcutaneous injection of 2.5 mg/kg diazepam (DZ), or (iii) iron, DZ with 800 mg/kg deferiprone intraperitoneal injections. The administration of DZ decreased mortality from 60 to 16% (p < 0.001). The addition of deferiprone to DZ resulted in zero mortality (p < 0.05 compared with the DZ group) over the study period. The administration of DZ was not associated with decreased iron absorption or increased urinary iron excretion, whereas the administration of deferiprone did result in urinary iron excretion. Microscopic examination suggests that diazepam administration may be associated with lower intracellular accumulation of iron. In conclusion, diazepam reduces mortality from iron overdose in rats through a yet unidentified mechanism, although the drug does not inhibit iron absorption or enhance urinary iron removal.

Original languageEnglish
Pages (from-to)895-899
Number of pages5
JournalCanadian Journal of Physiology and Pharmacology
Volume76
Issue number9
DOIs
StatePublished - 1998
Externally publishedYes

Keywords

  • Diazepam
  • Iron overdose
  • Rats

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