Combined histological and hematological assessment of iron-induced organ damage in a gerbil model of iron overload.

BACKGROUND: Previous studies with gerbil models have suggested that excessive iron exposure causes cardiomyopathy and hepatic injury, but pathological analysis was not comprehensive, preventing a detailed understanding of how the metal induces this damage. METHODS AND
RESULTS: Gerbils received single intraperitoneal injections of iron dextran (200 mg/kg) or saline and were then analyzed comprehensively for hematological and histological signs of organ damage. These tests included hematology parameters and determination of liver iron concentration, malondialdehyde levels and glutathione peroxidase activity; examination of heart and liver tissue stained with hematoxylin and eosin, Prussian-blue and Masson stain; and electron microscopy analysis of heart and liver ultrastructure. Iron-overloaded animals showed significantly different hematology parameters and significantly higher liver iron concentrations than saline-injected animals, as well as significantly higher malondialdehyde levels and significantly lower glutathione peroxidase activity. Histology analyses showed cellular damage, iron deposits, and both myocardial and liver fibrosis, while electron microscopy of heart and liver sections showed abundant iron deposition lysosomes, and disordered and swollen mitochondria. All these pathological changes increased with exposure time.
CONCLUSIONS: This comprehensive assessment of iron overload in a gerbil model suggests that excessive iron deposition induces extensive cellular damage, particularly fibrosis in heart and liver. This damage may be the direct result of iron-mediated lipid peroxide damage and of iron deposition that cause compression of myocardial and liver cells, as well as vascular occlusion.