Inhibition of pancreatic carboxypeptidase A: A possible mechanism of interaction between penicillic acid and ochratoxin A.
Penicillic acid and ochratoxin A are environmentally important toxic fungal metabolites (mycotoxins) that are synergistic in combination. The effects of penicillic acid on the pancreatic enzyme, carboxypeptidase A were investigated in vitro and in vivo. A broad range of inhibition in vitro of the enzyme by PA was demonstrated with a half-maximal inhibitory concentration equal to 1.1 x 10(-4) M PA. Inhibition of carboxypeptidase A was time and temperature dependent, and resulted in decreased conversion of parent ochratoxin A to the non-toxic metabolite, ochratoxin alpha. Studies in vivo demonstrated a penicillic acid-dependent inhibition of pancreatic carboxypeptidase A activity in the mouse and the chicken following multiple oral exposure. It is postulated that the mode of toxic interaction of the two mycotoxins may be due, in part, to impaired detoxification of ochratoxin A through penicillic acid depletion of carboxypeptidase A activity.
D000818:Animals; D002208:Caproates / Q000494:pharmacology*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D002645:Chickens; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009793:Ochratoxins / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology*; D010398:Penicillic Acid / Q000494:pharmacology*; D013045:Species Specificity; D013997:Time Factors
D002208:Caproates; D009793:Ochratoxins; C025589:ochratoxin A; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D010398:Penicillic Acid