Renal Histopathological Responses to Nephrotoxic <i>Penicillium aurantiogriseum</i> in the Rat during Pregnancy, Lactation and after Weaning

Abstract

The typical renal histopathological changes in proximal tubules of rats consuming food containing shredded wheat moulded by Penicillium aurantiogriseum did not occur in neonates of rats ingesting the nephrotoxic diet during pregnancy nor in pups fed only by lactation from a treated dam. In contrast, weanlings consuming the moulded diet consistently showed within a few days densely staining mitosis-like structures in the proximal tubules which was the first step leading to development of the prominent tubular cytomegaly and karyomegaly seen when 16 weeks old. Karyomegaly and cytomegaly became evident also when mouldy shredded wheat constituted only 1% of a diet consumed on 45 days during the first 8 weeks after weaning, demonstrating the potency of the active component. Relevance to the putative involvement of nephrotoxic mycotoxins in human renal disease is discussed, as is the apparent absence of a renal histopathological response in adult rats during pregnancy and lactation.

Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

“…However, experimental animals are not always perfect models for humans. Therefore, the contrast between the striking renal histopathological response in the rat to four days of dietary administration of extract of wheat moulded by Penicillium polonicum , and the absence of any adverse response in a vervet monkey to 10 days of nasogastric administration of the same extract to a cumulative 5-fold greater dose than in the rat on a body weight basis, [31,32] may be a relevant consideration. …”

“…Rat tissues were in wax blocks archived at Imperial College London mainly during the past decade and mostly from published experimentation [6,8,10,11,12,28,32], with tumour illustration cited in the Supplementary Data Table S1). Similarly archived human tumour tissues were from Denmark (a metastasising renal cell carcinoma [9]) and Romania (County Hospital, Timisoara; four transitional cell carcinomas from cases of Balkan endemic nephropathy [9]); details of their histopathology and DNA ploidy distribution have also been published [9].…”

A critical review of producers of small lactone mycotoxins: patulin, penicillic acid and moniliformin

“…Penicillium polonicum and Penicillium aurantiogriseum, both producing penicillic acid, verrucosidin and nephrotoxic glycopeptides, are often found in the Balkan countries, but Penicillium verrucosum, the main ochratoxin A producing Penicillium species in cereals, is found less often (MacGeorge and Mantle, 1990;Mantle, 1994;Mantle et al, 2010;Miljkovic et al, 2003;Stoev et al, 2010;Yeulet et al, 1988). Penicillic acid is mostly found in cereals (Bokhari and Flannigan, 1996;Chełkowski and Golinski, 1983;Chełkowski et al, , 1987Kurtzman and Ciegler, 1970;Szebiotko et al, 1981;Tangni and Pussemier, 2007) and some other products like cassava (Wareing et al, 2001).…”

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

“…Chemical characterisation of the nephrotoxin is still incomplete, although it is water-soluble and amphoteric, and may be a peptide [11]. Weanling rats of both sexes are susceptible, responding to ingestion of contaminated feed within a few days by mitoses in proximal tubule epithelium progressing to striking diffuse karyocytomegaly distributed mainly throughout the outer stripe of the outer medulla [12,13,14,15]. In contrast, there was no similar response in the hamster [16].…”