An ultrastructural investigation of nephrotoxicity in rats induced by feeding cultures of Penicillium verrucosum var. cyclopium.

A renal tubular lesion was induced in male rats by giving them a culture homogenate or culture filtrate of Penicillium verrucosum var. cyclopium by gastric gavage for 20 days. The fungus was obtained from stored maize in an area of endemic nephropathy in Bulgaria. Changes in the proximal convoluted tubules were studied by light and electron microscopy. The lesion was confined to the pars recta in the outer stripe of the outer zone of the medulla. It consisted of degeneration and necrosis of epithelial cells, prominent karyomegaly, arrested mitotic divisions and production of binucleate and tetranucleate tubular cells. Two patterns of degeneration occurred with comparable frequency: a vesicular form with pyknotic nucleus and electron lucent degeneration. Nuclei of the epithelial cells in affected tubules contained segregated nucleoli. The necrotic cells were replaced by actively regenerating cells derived from adjacent viable epithelium. The similarity between the tubular lesions induced in rats and the changes found in patients with Balkan endemic nephropathy is discussed.