The Effect of Prenatal Indium Chloride Exposure on Chondrogenic Ossification

Abstract

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.

Developmental toxicity of indium: Embryotoxicity and teratogenicity in experimental animals

“…These findings obtained by in vitro experiments, as described above, also indicated that the embryotoxicity of indium could have direct effects on the conceptuses. The inhibited activity of chondrocytes (Ungváry et al. 2001) in rat fetuses caused by the maternal administration of indium may be responsible for indium‐induced skeletal malformation.…”

Atomic spectrometry update. Clinical and biological materials, foods and beverages

“…In a study to examine the toxic effects of In on prenatal bone development in rats, Ungvary and coworkers 142,143 determined In levels in maternal and fetal blood, liver, kidney, skull and femur by AAS, following daily oral administration of In to pregnant rats. Indium concentrations were observed to increase significantly in blood and tissues of the mother 4 h after administration of In.…”