Evaluation of Liver Toxicity of 2-Methyl-3-Hydroxypyridin-4-one in Iron Overloaded Rats

Hydroxypyridinone iron chelators are currently the main candidates fordevelopment 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 andcompared with those of dfo. for iron overloading, rats received i.p. injections of100 mg/kg of iron-dextran twice a week for 4 consecutive weeks. they wereallowed for equilibration of iron after overloading for 15 days. then the ratsreceived i.p. injections of 200 mg/kg/day of either mhpo or dfo for 15 days. atthe end of this period, blood samples were taken and the iron and ferritinconcentrations, and the total iron binding capacity (tibc) were determined. theactivities of sgot, sgpt and alp were analyzed by standard colorimetric kits.serum values for iron, tibc and ferritin were shown to have no significantdifferences after the administration of either mhpo or dfo in treated rats. sgotand sgpt values were significantly reduced after the administration of mhpo. dfo,however, was only able to reduce sgpt with the same dose. there were nosignificant differences between two chelators with regards to alp. after theadministration 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 atmobilizing iron, and reduces liver toxicity, however, with regard to other sideeffects such as its skin toxicity, further studies are required.