Renal Apoptosis in the Mycotoxicology of Penicillium polonicum and Ochratoxin A in Rats

Abstract

Penicillium polonicum K. M. Zaleski, which is common on foodstuffs in Balkan regions that are notable for their history of endemic nephropathy, has been shown experimentally to cause a striking histopathological renal change in rats that are given feed contaminated by this fungus. The nephrotoxic agent(s) are only partially characterized. The principal change seen in the cortico-medullary region is karyocytomegaly, but apoptosis, identified with the ApopTag® methodology, is the first response to a dietary extract of P. polonicum-molded wheat after a few days of exposure. Chromatin debris migrates along the nephrons into the medulla, but whether the damaged epithelial fate is via autophagy is unclear. In intermittent exposure experiments, renal apoptosis was resolved with the cessation of exposure and was restored with renewed exposure. Apoptosis became less evident after 3 months of chronic exposure. In contrast, a relatively high dose of dietary ochratoxin A, a potent nephrocarcinogen in male rats after many months of dietary exposure, gave no evidence of apoptosis in asymptomatic weanlings over a few days of dietary exposure. This was attributed to a masking effect by concomitant marked histological disruption in renal tissue. However, in young adults, renal apoptosis was a primary outcome of dietary exposure to either the P. polonicum extract or to ochratoxin A, but the histopathological response to the former was less distorted. The apparent conflicted use in the literature of P. polonicum as a descriptor is highlighted.