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

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.

Efficacy of deferiprone in the treatment of acute iron intoxication in rats.

BACKGROUND: Deferiprone [(1,2-dimethyl-3-hydroxypyrid-4-one) (L1)], is the first orally active iron chelating agent to reach clinical trials in patients with chronic iron overload. Its efficacy in preventing morbidity and mortality in acute iron poisoning has not been tested. OBJECTIVE: To determine whether deferiprone can reduce the mortality of rats following toxic oral doses of iron. METHODS: Rats were administered 612 mg/kg elemental iron by gavage, corresponding to the LD58. A parallel group received the same oral dose of iron followed by deferiprone intraperitoneally at 400 mg/kg (loading dose), followed by additional intraperitoneal injections of 200 mg/kg, 100 mg/kg and 100 mg/kg of deferiprone at one hour intervals. RESULTS: Coadministering deferiprone with the iron decreased mortality from 58% (11/19) to 15% (3/20) (p = 0.013). The administration of deferiprone was associated with urinary excretion of iron (which did not occur with iron alone) and the production of the red deferiprone-iron complex. On histological examination there appeared to be less iron in the liver and gastrointestinal tract. CONCLUSION: The coadministration of deferiprone can decrease morbidity and mortality caused by acute iron overdose. Deferiprone holds promise for the treatment of iron poisoning but additional study is required.