Contrasting Nephropathic Responses to Oral Administration of Extract of Cultured Penicillium polonicum in Rat and Primate

Liquid- or solid substrate-cultured Penicillium polonicum administered in feed to rats over several days evokes a histopathological response in kidney involving apoptosis and abnormal mitosis in proximal tubules. The amphoteric toxin is yet only partly characterized, but can be isolated from cultured sporulating biomass in a fraction that is soluble in water and ethanol, and exchangeable on either anion- or cation-exchange resins. After several weeks of treatment renal proximal tubule distortion became striking on account of karyocytomegaly, but even treatment for nearly two years remained asymptomatic. Extract from a batch of solid substrate fermentation of P. polonicum on shredded wheat was incorporated into feed for rats during four consecutive days, and also given as an aqueous solution by oral gavage to a vervet monkey daily for 10 days. Treatment was asymptomatic for both types of animal. Rat response was evident as the typical renal apoptosis and karyomegaly. In contrast there was no such response in the primate; and neither creatinine clearance nor any haematological characteristic or serum component concentration deviated from a control or from historical data for this primate. The contrast is discussed concerning other negative findings for P. polonicum in pigs and hamsters. Renal karyomegaly, as a common rat response to persistent exposure to ochratoxin A, is not known in humans suspected as being exposed to more than the usual trace amounts of dietary ochratoxin A. Therefore the present findings question assumptions that human response to ochratoxin A conforms to that in the rat

A Penicillium nephrotoxin and associated metabolites in the aetiology of Balkan nephropathy

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Quinazolin-4-one coupled with pyrrolidin-2-iminium alkaloids from marine-derived fungus Penicillium aurantiogriseum

Three new alkaloids, including auranomides A and B (<strong>1</strong> and <strong>2</strong>), a new scaffold containing quinazolin-4-one substituted with a pyrrolidin-2-iminium moiety, and auranomide C (<strong>3</strong>), as well as two known metabolites auranthine (<strong>4</strong>) and aurantiomides C (<strong>5</strong>) were isolated from the marine-derived fungus <em>Penicillium aurantiogriseum</em>. The chemical structures of compounds <strong>1</strong>–<strong>3</strong> were elucidated by extensive spectroscopic methods, including IR, HRESIMS and 2D NMR spectroscopic analysis. The absolute configurations of compounds <strong>1</strong>–<strong>3</strong> were suggested from the perspective of a plausible biosynthesis pathway. Compounds <strong>1</strong>–<strong>3</strong> were subjected to antitumor and antimicrobial screening models. Auranomides A–C exhibited moderate cytotoxic activity against human tumor cells. Auranomides B was the most potent among them with an IC<sub>50</sub> value of 0.097 μmol/mL against HEPG2 cells