evaluation of liver toxicity of 2-methyl-3-hydroxypyridin-4-one in iron overloaded rats
نویسندگان
چکیده
hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (dfo). in the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (mhpo), was studied in iron overloaded rats and compared with those of dfo. for iron overloading, rats received i.p. injections of 100 mg/kg of iron-dextran twice a week for 4 consecutive weeks. they were allowed for equilibration of iron after overloading for 15 days. then the rats received i.p. injections of 200 mg/kg/day of either mhpo or dfo for 15 days. at the end of this period, blood samples were taken and the iron and ferritin concentrations, and the total iron binding capacity (tibc) were determined. the activities of sgot, sgpt and alp were analyzed by standard colorimetric kits. serum values for iron, tibc and ferritin were shown to have no significant differences after the administration of either mhpo or dfo in treated rats. sgot and sgpt values were significantly reduced after the administration of mhpo. dfo, however, was only able to reduce sgpt with the same dose. there were no significant differences between two chelators with regards to alp. after the administration of mhpo, skin rashes were observed in a way that rats could not move. in conclusion, this study confirms that mhpo is at least as effectives as dfo at mobilizing iron, and reduces liver toxicity, however, with regard to other side effects such as its skin toxicity, further studies are required.
منابع مشابه
Evaluation of Liver Toxicity of 2-Methyl-3-Hydroxypyridin-4-one in Iron Overloaded Rats
Hydroxypyridinone iron chelators are currently the main candidates for development of orally active iron chelating alternatives to desferrioxamine (DFO). In the present study, the relative efficacy and liver toxicity of a bidentate chelator, 2-methyl-3-hydroxypyridin-4-one (MHPO), was studied in iron overloaded rats and compared with those of DFO. For iron overloading, rats received i.p. ...
متن کاملComparison of the subacute toxicity and efficacy of 3-hydroxypyridin-4-one iron chelators in overloaded and nonoverloaded mice.
Five orally effective iron chelators of the 3-hydroxypyridin-4-one series have been administered intraperitoneally to iron-overloaded and nonoverloaded male mice at a dose of 200 mg/kg/24 h for a total of 60 days to investigate the effect on iron loading and toxicity. There was a significant reduction in hepatic iron at the end of the study in the iron-overloaded mice with all compounds studied...
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The relationship between the oral efficacy and the acute toxicity of hydroxypyridin4one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing “Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded...
متن کاملRelative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice.
The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloa...
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عنوان ژورنال:
iranian journal of pharmaceutical sciencesجلد ۲، شماره ۱، صفحات ۳۵-۴۰
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