engleski

Ochratoxin A is an effective inhibitor of phenylanine hydroxylase in vivo

Ochratoxin A (OA) is a nephrotoxic, hepatotoxic and teratogenic mycotoxin produced by storage moulds (e.g. by species of Aspergillus and Penicillium) on a variety of foodstuff of vegetable and animal origin. Exposure to low concentrations of OA causes morphological and functional changes in kidney of experimental animals, similar to those found in Balkan endemic nephropathy. Chemical structure of OA involves 5'chlorinated-3, 4-dihydro-3-methylisocumarin moiety (OA-alfa) linked to 1-phenylalanine, what makes OA a potential inhibitor of phenylanine hydroxylase (PAHase). We have examined the effects of low doses of OA on the activity of PAHase in kidney and liver of experimental animals. Daily administration of OA in doses of 120 mikrograms/kg b.w. caused a significant drop in enzyme activity already after 10 days of treatment. The activity decreased from the control value of 32.5 + 2.66pmol/min/mg prot. to 18.03 + 1.8 pmol/min/mg prot. Decrease in the enzyme activity was followed by a concentration increase of phenylalanine in liver, kidney, serum and urine. Similar inhibition of PAHase was found in kidney. Prolonged treatment (35 days) with OA resulted in even further enzyme inhibition, in both, liver and kidney tissues. Acute toxicity of OA and phenylalanine (dose 1200 mikrograms/kg b.w.) could be reduced by simulataneous application of OA and phenylalanine (dose 1200 mikrograms/kg b.w.). Inhibition of PAHase was significantly reduced, almost to the normal activity (25.1 + 1.6 pmol/min/mg prot.). The increased PAHase activity was followed by reduction of the concentration of phenylalanine in serum and tissues. The results suggest that phenylalanine and OA may compete on the PAHase and that a treatment with phenylalanine may improve toxic changes produced by OA.

ochratoxin A; kidney; liver; phenylalanine; phenylalanine hydroxylase

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