The effect of prenatal indium chloride exposure on chondrogenic ossification.
Daily indium chloride doses of control (0) or 400 mg/kg were administered orally to pregnant Sprague-Dawley (SD) rats by gavage, on d 20 of gestation. Indium concentration was determined in the maternal and fetal blood, livers, kidneys, skulls, and femurs by atomic absorption spectrometry. Further groups of pregnant rats were treated with control (0) or 400 mg/kg indium chloride orally, during the whole gestation period. The fetuses were examined on d 21 of gestation, using histological and histochemical methods. Four hours after the administration indium concentration was found to be significant in the blood, liver, and kidneys of the dams. Twenty-four hours later it increased in the blood but not in the liver and kidney. Fetal indium concentrations were 40-50% of the maternal levels due to a barrier of the placenta. In the skull and the femur, indium was already detectable at 4 h after the administration, and by the end of 24 h, metal concentration was several times higher than that at 4 h, indicating accumulation. Furthermore, it was found that the birefringency of collagen detectable by picrosirius red staining in polarized light around the chondrocytes disappeared and became irregular. In the matrix of the epiphyseal cartilage, the regular, birefringent network demonstrable by Rivanol reaction became irregular and hardly recognizable. In the cytoplasm of the chondrocytes, the diffuse, evenly distributed positive Ricinus communis agglutinin reaction became irregular or disappeared. Similar but much weaker changes were observed with concanavalin A and wheat germ agglutinin stainings. It was concluded that the missing femur and micromelia diagnosed by alizarin staining is the consequence of a specific toxic effect of indium that inhibits chondrogenic ossification. No similar histochemical changes were observed in the bones of the skull developing by desmogenic ossification, despite the presence of indium. Data indicate that the mechanisms of the effects of indium causing retardation and/or malformation differ in the bones developing through desmogenic or chondrogenic ossification.
Ungváry
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József Fodor National Center for Public Health, Budapest, Hungary. ungvary@elender.hu
Tátrai
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Szakmáry
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E
Náray
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M
D000818:Animals; D000880:Anthraquinones; D001846:Bone Development / Q000187:drug effects*; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000254:growth & development* / Q000473:pathology*; D004396:Coloring Agents; D005260:Female; D007204:Indium / Q000493:pharmacokinetics / Q000633:toxicity*; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000254:growth & development / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000880:Anthraquinones; D004396:Coloring Agents; D007204:Indium; C020758:indium trichloride; C010078:alizarin