Chelation of bismuth by combining desferrioxamine and deferiprone in rats

• Published in: Toxicology and industrial health Vol. 24; no. 4; pp. 235 - 240
• Main Authors: Tubafard, S, Fatemi, SJ
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01-05-2008; Sage Publications Ltd
• Subjects: Animals; Bismuth - metabolism; Bismuth - pharmacokinetics; Bismuth - toxicity; Body Weight - drug effects; Chelation Therapy - methods; Deferoxamine - therapeutic use; Drug Therapy, Combination; Eating - drug effects; Iron - analysis; Iron - metabolism; Iron Chelating Agents - therapeutic use; Kidney - metabolism; Male; Pyridones - therapeutic use; Rats; Rats, Wistar; Siderophores - therapeutic use; deferiprone; desferrioxamine; chelation; bismuth chelators; iron; bismuth rats; bismuth
• ISSN: 0748-2337; 1477-0393
• DOI: 10.1177/0748233708095771

Consumption and production of bismuth compounds are increasing, however, a little information on the toxic effect and also the effective method in removal of bismuth compounds are available. The present research aimed to characterize the potential efficiency of two chelators after bismuth administration for 55 days following two dose levels of 20 and 40 mg/kg body weight daily to male rats. However, we found abnormalities after bismuth administration in clinical signs, such as body weight, kidneys and liver damages, a black line on gums and skin reactions. Furthermore, the hypothesis that the two chelators might be more efficient as combined therapy than as single therapy in removing bismuth from the body was considered. Along this line, two known chelators deferiprone (1, 2-dimethy1-3-hydroxypyride-4-one, L1) and desferrioxamine (DFO) were chosen and tested in the acute rat model. Chelators were given orally (L1) or intraperitoneally (DFO) as a single or combined therapy for the period of a week. Doses of L1 and DFO were 110 mg/kg body weight in experiments. Bismuth and iron concentrations in various tissues were determined by graphite furnace and flame atomic absorption spectrometry, respectively. The combined chelation therapy results show that DFO and L1 are able to remove bismuth ions from the body, whereas iron concentration returned to the normal level and symptoms are also decreased. DFO was more effective than L1 in reducing bismuth concentration in tissues. The efficiency of DFO + L1 is more than DFO or L1 in removing bismuth from organs. Our results are indicative that the design procedure might be useful for preliminary in-vivo testing of the efficiency of chelating agents. Results of combined chelators’ treatment should be confirmed in a different experimental model before extrapolation to other systems. This testing procedure of course does not provide all the relevant answers for efficiency of chelating agents in bismuth toxicity.