Spontaneous Iron Overload in Sprague-Dawley Rats

In a review of the toxicological studies performed in our laboratory during the period 1986-1995, we occasionally observed significant iron overloading in the liver. Liver tissue was examined by light and electron microscopy, and the results were analyzed by sex and age (7, 9, 11, 19, 31, 59, and 111 wk). The intensity of iron overload increased with age: the accumulation began in pericanalicular siderosomes of periportal hepatocytes and extended progressively to the entire lobule and also to nonhepatocytic cells (Kupffer cells in sinusoids and macrophages around bile ducts in portal tracts) and occasionally with distortion of sinusoids by sideroblastic nodules and moderate enlargment of portal tracts in the oldest animals. No significant inflammatory infiltrates, degeneration, necrosis or fibrosis were noted. Hepatocyte pigmentation alone was prominent at 9 and 11 wk. The frequency of pigmentation of parenchymal and nonhepatocytic cells increased from 9 wk for females; in males, this was seen only at 111 wk. The intensity of pigmentation of nonhepatocytic cells versus parenchymal cells increased with aging. The frequency of those different types of iron overloading was higher for females up to 111 wk. The pathology of spontaneous iron overloading in the Sprague-Dawley rat, described here in spite of differences, has some similarities to that of human hereditary hemochromatosis.