Comparative responses to mode of oral administration and dose of ochratoxin A or nephrotoxic extract of Penicillium polonicum in rats

Administration of Penicillium polonicum extract to male Sprague-Dawley rats (200 g), either mixed in feed or given daily by gavage, for 5 days, had no clinical effects. However, at necropsy on day 6 marked histopathological changes occurred in renal tubule epithelia, including mitotic figures, karyomegalic nuclei, and frequent apoptosis identified specifically by TUNEL methodology and confocal microscopy. Ochratoxin A given similarly to rats (daily, 1mg or 0.2mg) was also clinically asymptomatic except for the 1mg dose given by gavage; rats in this group lost weight. Marked renal tubular necrosis, though even without any significant accompanying apoptosis, was evident only at this higher dose by gavage; it was associated also with the highest incidence of renal DNA adducts and a disproportionately high concentration of ochratoxin A in plasma on day 6. Significantly fewer renal DNA adducts were detected in rats given 1mg ochratoxin A in feed. The study demonstrates the potential for exaggerated toxicological responses to ochratoxin A administered by gavage through predicted consequential surges in the circulating concentration of the mycotoxin.