Mechanism of action of ochratoxin A.

摘要: Ochratoxin A has a number of toxic effects in mammals, the most notable which is nephrotoxicity. It also immunosuppressive, teratogenic and carcinogenic. The biochemical molecular aspects its action were first studied bacteria. appearance 'magic spots' (ppGpp pppGpp) pointed to inhibition charging transfer ribonucleic acids (tRNA) with amino acids. This suggestion was confirmed by demonstration that ochratoxin inhibits bacterial, yeast liver phenylalanyl-tRNA synthetases. competitive phenylalanine reversed an excess this acid. As consequence, protein synthesis inhibited, as shown hepatoma cells culture, Madin Darby canine kidney (which are much more sensitive) vivo mouse liver, spleen, being effective latter two organs. An prevents cell cultures vivo. Analogues been replaced other have similar inhibitory on respective acid-specific aminoacyl tRNA 4R-Hydroxyochratoxin A, metabolite action, whereas alpha (the dihydroisocoumarin moiety) B (ochratoxin without chlorine) no effect. might act enzymes use substrate. We showed recently it hydroxylase. In addition, moiety partially hydroxylated tyrosine incubation hepatocytes explain why acid immuno-suppressive effect nephrotoxic actions. followed RNA synthesis, affect proteins high turnover. lowers level phosphoenolpyruvate carboxykinase, key enzyme gluconeogenesis; reported be due specific degradation mRNA codes for enzyme. Recently, found enhance lipid peroxidation both vitro important or mitochondrial membranes responsible mitochondria several authors. Finally, recent results Pfohl-Leszkowicz et al. (this volume), who formation DNA adducts mainly but single-strand breaks observed previously mice rats after acute chronic treatment.