A comparative study on the gastroduodenal tolerance of different antianaemic preparations.
The most significant adverse effect of repeated oral administration of iron-containing antianaemic preparations is the gastroduodenal toxicity, attributable to a direct toxic effect of iron on the glandular epithelium. To assess gastroduodenal mucosal damage and the potential protective effect of different antianaemic preparations, a study was carried out to compare the gastroduodenal toxicity caused by three different types of antianaemic drugs in normal and anaemic rats administered at repeated therapeutic doses. Histological damage to the gastroduodenal mucosa was evaluated using light and electron microscopy. In both normal and anaemic rats, pathological changes were less marked in animals treated with ferrimannitol-ovoalbumin (TM/FMOA) than in those treated with iron protein succinylate or ferrous sulphate. Electron microscopic studies of duodenal mucosa in normal rats treated with iron protein succinylate and ferrous sulphate confirmed a severe ultrastructural alteration, whereas no changes were detected in animals treated with TM/FMOA. In anaemic rats, slight duodenal ultrastructural changes were noted with all three types of treatment. The effectiveness of the preparations in resolving the anaemia was similar in the three groups. It was concluded that TM/FMOA exerts a protective effect against the toxicity normally observed of the iron in other formulations in normal and anaemic rats, which was attributed to the fact that administration of iron bound to a protein core allows for gradual release of iron.
Experimental and Preclinical Toxicology Laboratory, Applied Pharmacobiology Research Centre (CIFA), Department of Pathology and Toxicology, University of Navarra, Pamplona, Spain. maidoate@unav.es
M A
MA
Idoate Gastearena
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AG
Gil
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Azqueta
M P
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Coronel
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Gimeno
D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D003692:Delayed-Action Preparations; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D007501:Iron / Q000097:blood; D008297:Male; D008353:Mannitol / Q000737:chemistry; D008667:Metalloproteins / Q000008:administration & dosage / Q000009:adverse effects*; D008854:Microscopy, Electron; D051381:Rats; D017208:Rats, Wistar; D013386:Succinates / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors
D003692:Delayed-Action Preparations; D005290:Ferric Compounds; D005296:Ferrous Compounds; D008667:Metalloproteins; D013386:Succinates; C020748:ferrous sulfate; D008353:Mannitol; D007501:Iron; C055066:iron protein succinylate