Studies on fungal nephrotoxicity. 2. Isolation of two nephrotoxic compounds from Penicillium viridicatum Westling: citrinin and oxalic acid.

Nephrotoxic compounds were isolated from a strain of Penicillium viridicatum Westling. This strain was isolated from a batch of barley which by feeding caused a chronic kidney degeneration in pigs and rats. Liquid corn steep medium was inoculated and incubated as stationary culture. After fractionation of the liquid medium fractions and isolated compounds were perorally administered to rats during a period of 2–3 weeks. Two compounds were found nephrotoxic: Citrinin and oxalic acid. Oxalates cause in rats during a long-term experiment a chronic kidney damage, characterized by dilated tubules, formation of cysts and connective tissue and crystals of calcium oxalate in the tubules. No nuclear alterations were observed. Citrinin-induced kidney damage is characterized by enlarged kidneys. Degeneration of the proximal tubules in the form of hydropic degeneration, loss of brush border, and pyknotic nuclei are observed. These lesions are accompanied by thickening of the tubular basement membranes, activation of interstitial cells and formation of collagen. Some tubules are dilated into cysts. This kidney degeneration is comparable to the kidney damage in rats and pigs caused by feeding barley inoculated with P. viridicatum as well as by feeding the batch of barley from which the fungus was isolated. The kidney damage in pigs is comparable to the chronic kidney degeneration observed among Danish pigs fed mouldy feed. Thus it is assumed that the kidney degeneration naturally occurring among Danish pigs is a mycotoxicosis caused by citrinin, although a synergistic effect with other compounds may exist.