Ochratoxin A and citrinin are nephrotoxic mycotoxins found in a variety of foods and feeds. Before studying possible interactions between these two toxins, their individual biochemical effects were examined in vitro by using renal cortical explants derived from male swine of the Hormel-Hanford strain. The following measurements were performed: macromolecule biosynthesis (protein, RNA, and DNA), respiration (14CO2 from [14C]glucose), organic ion (tetraethyl ammonium acetate, i.e., TEA) transport, and membrane perturbation (protein leakage into medium). Levels of the toxins ranged from 0.001 to 1 mM. Ochratoxin A inhibited macromolecule biosynthesis at a lower concentration (0.001 mM) than did citrinin. Protein and DNA synthesis were particularly sensitive to ochratoxin A. Syntheses of protein and DNA were inhibited at ochratoxin A concentrations of 0.01 and 0.001 mM, respectively. RNA synthesis was less sensitive to the mycotoxin; it was inhibited only 60% at 1 mM, the highest concentration of ochratoxin A tested. Citrinin levels of 0.01 mM were required for inhibition of RNA, DNA, and protein synthesis. Inhibition by citrinin was approximately equal for all three classes of macromolecules. Citrinin was more effective than ochratoxin A in the inhibition of respiration and TEA transport; the minimum effective levels of citrinin were 1 and 0.01 mM, respectively. Serious membrane damage as evidenced by increased protein leakage was not caused by either toxin. Stimulation of respiration, perhaps reflective of uncoupling of oxidative phosphorylation, was produced by an ochratoxin A concentration of 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS)

The mycotoxins citrinin and ochratoxin A are produced in common by some molds and have been found together in a number of foods and animal feeds. We used in vitro tests to determine if the same effects are produced by these two mycotoxins when they act both independently and together. Renal cortical cubes prepared from kidneys of young adult Hormel-Hanford miniature swine were cultured in the presence or absence of the toxins for 1 h at 37 degrees C. The concentration of the toxins both singly and in combination ranged from 10(-6) to 10(-3) M. The tissues were incubated, removed, rinsed, and reincubated to measure transport of either tetraethylammonium (TEA) or paraminohippurate (PAH) ions and protein synthesis, using 3H-leucine. The transport data were analyzed by a recently developed logistic function test to ascertain whether the effects were additive, synergistic, or antagonistic. The significance of deviation was tested after a potency multiplier was added to the mixture. Data for three of the five experiments measuring TEA transport indicated a synergistic effect; for the other two, the results were not significantly different from additivity. The same was true for PAH transport. For protein synthesis, one experiment showed synergism; for the other, nonadditivity was not significant. None of the measurements showed antagonism between the two toxins. As with several other systems, tests of biochemical effects showed that administration of citrinin and ochratoxin A together did not elicit either consistent or strong synergistic responses.