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, 1 mg or 0.2 mg) was also clinically asymptomatic except for the 1 mg 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 1 mg 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.
Miljkovic
Ana
A
Biochemistry Department, Imperial College of Science, Technology and Medicine, London, UK.
Pfohl-Leszkowicz
Annie
A
Dobrota
Miloslav
M
Mantle
Peter G
PG
D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007673:Kidney Cortex Necrosis / Q000139:chemically induced / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000633:toxicity*; D009793:Ochratoxins / Q000008:administration & dosage / Q000633:toxicity*; D010407:Penicillium; D051381:Rats; D017207:Rats, Sprague-Dawley
D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A