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

Abstract

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.

Contribution of Organ Vasculature in Rat Renal Analysis for Ochratoxin A: Relevance to Toxicology of Nephrotoxins

“…There is also the elusive silent nephropathic metabolite of the common food-borne mould Penicillium polonicum , causing rat renal apoptosis and one DNA adduct [ 35 ]. Chronic ingestion results in striking karyomegaly in the outer stripe of the outer medulla [ 36 ], a histopathological feature of topical interest also for OTA carcinogenicity [ 37 ].…”

Rat Kidney Cancers Determined by Dietary Ochratoxin A in the First Year of Life

“…This focuses on proximal tubules in the outer stripe of the outer medulla (OSOM) in response to a Penicillium polonicum –moulded wheat extract, causing striking karyocytomegalic changes in the rat but no response in a vervet monkey (15). Karyomegaly is widespread within OTA renal tumours (1).…”

“…To illustrate that rat responses do not automatically translate to the human, and concerning the renal karyomegaly found in OTA-treated rats, it is difficult to ignore contrasting findings in another mycotoxin-induced nephrotoxicity. This focuses on proximal tubules in the outer stripe of the outer medulla (OSOM) in response to a Penicillium polonicum –moulded wheat extract, causing striking karyocytomegalic changes in the rat but no response in a vervet monkey ( 15 ). Karyomegaly is widespread within OTA renal tumours ( 1 ).…”

Comments on “Mycobiota and Mycotoxins in Traditional Medicinal Seeds from China. Toxins 2015, 7, 3858-3875”— in Attributing Ochratoxin A Biosynthesis Within the Genus Penicillium Occurring on Natural Agricultural Produce

“…The fungus has also been isolated from meat products across several Mediterranean latitudes. P. polonicum was the most abundant mould contaminant in previous Balkan nephropathy studies [ 2 , 3 ]; although never found to produce OTA, it did commonly produce a novel nephrotoxin, expressed notably in the rat but not the primate [ 15 , 16 , 17 , 18 ]. It would be interesting if this species in China has similar toxigenic potential.…”