Ochratoxin A-induced porcine nephropathy: enzyme and ultrastructure changes after short-term exposure

Four pigs were treated with ochratoxin A (800 micrograms/kg) for five consecutive days. Subsequently, urine and bile were collected and kidneys were perfusion fixed unilaterally. Liver and kidney samples were examined for the distribution of ochratoxin A and metabolites in subcellular fractions and the effects of the toxin on protein synthesis and enzyme activities. Ochratoxin A and the hydrolytic product, ochratoxin alpha, were found in urine. Elevated levels of toxin accumulation in kidney (283 ng/g) compared with liver (189 ng/g) and toxin-mediated reductions in protein synthesis and enzyme activities in kidney identified it as a target organ of ochratoxin toxicity. Ultrastructural investigations of kidney in toxin-exposed animals identified a process of condensation of cellular material with disappearance of membranes and continuous desquamation in the lower part of the proximal convoluted tubules. In target cells peroxisomes appeared to have lost membrane integrity and the organelles were leaking materials into the cytosol. Reduction of structural integrity was associated with an increase in the presence of catalase and cyanide insensitive fatty acid oxidase activity in the soluble kidney fractions.