Ochratoxin A impairs activity of the membrane bound enzymes in rat pancreas

Ochratoxin A is a mycotoxin produced by Aspergillus ochraceus and is a natural contaminant of moldly food. Ochratoxin A has a number of toxic effects, some of which may be related to the changes in the cell membrane. We measured the activities of 5 pancreatic, membrane bound enzymes in female Fisher rats that were given low oral doses of ochratoxin A (120 micrograms/kg body weight per day) during 20-35 days. The amount of toxin corresponds to 1.5 mg/kg in the feed, daily. These doses are in the range of natural contamination found in feed. The enzymes studied were alanine aminopeptidase, alkaline phosphatase, ecto-Ca2+/Mg(2+)-ATPase, gamma-glutamyl transferase and ecto-5'-nucleotidase. Treatment lasting 20 days caused a strong decrease in the activity of alanine aminopeptidase, Ca2+/Mg(2+)-ATPase and alkaline phosphatase to 0.76 +/- 0.04, 0.53 +/- 0.03 and 0.30 +/- 0.02 of the control values, respectively (p < 0.05). No significant changes in the activity of gamma-glutamyl transferase and 5'-nucleotidase were observed. However, activity of alanine aminopeptidase returned to normal values after 35 days of treatment, suggesting an adaptation of the organism, or a substitution of a released enzyme. Activities of alkaline phosphatase and Ca2+/Mg(2+)-ATPase remained significantly reduced to 0.42 +/- 0.03 and 0.52 +/- 0.04, respectively (p < 0.01). We conclude that treatment of rats with low doses of ochratoxin A resulted in reduction of the activities of the membrane bound enzymes, most probably by inducing their release, as a result of the impairment of the functional integrity of cell membranes.