title: Acute histopathological changes produced by Penicillium aurantiogriseum nephrotoxin in the rat.
abstract: Shredded wheat moulded by an isolate of Penicillium aurantiogriseum elicited progressive histopathological changes at the rat renal cortico-medullary junction during 5 days of dosing, when incorporated into diet as a 20% component. The changes of acute tubular necrosis and regeneration were seen in the P3 segment of the nephron. In rats exposed to contaminated diet for 5 days the histopathological changes regressed in severity by about one-half within a further 4 days on normal diet and by 7 days the tubular epithelium was nearly normal. A partially purified fraction of an alcohol extract, selected by preparative high-voltage electrophoresis and anion exchange and notably rich in amino-compounds, was typically nephrotoxic when given in diet over 4 days. Acute marked tubular necrosis also occurred when the same fraction was given intraperitoneally over a similar period. The acute histological changes provide a rapid bioassay for this Penicillium nephrotoxicity and facilitate the search for the toxic metabolite(s). The cumulative expression of necrosis and repair over only a few days in tubular epithelium suggests that chronic exposure will elicit a more complex pathology which might serve as an experimental model for the idiopathic Balkan endemic nephropathy.
authors.affiliation: Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Adatia
authors.forename: J M
authors.initials: JM
authors.lastname: Heaton
authors.forename: K M
authors.initials: KM
authors.lastname: Macgeorge
authors.forename: P G
authors.initials: PG
authors.lastname: Mantle
mesh_terms: D000818:Animals; D001449:Balkan Nephropathy / Q000139:chemically induced / Q000473:pathology*; D005516:Food Microbiology; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000473:pathology*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000473:pathology; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000506:poisoning*; D010407:Penicillium / Q000472:pathogenicity*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009183:Mycotoxins