Inhibition of liver, kidney, and erythrocyte δ-aminolevulinic acid dehydratase (porphobilinogen synthase) by gallium in the rat

摘要: Selective inhibition of enzymes in the heme biosynthesis pathway with concomitant urinary excretion precursors serve as potentially important biological markers chemical exposure and cell injury. Intratracheal administration gallium arsenide particulate suspensions has been shown to result delta-aminolevulinic acid dehydratase (ALAD) several tissues increased precursor aminolevulinic (ALA). This study was undertaken evaluate vivo role alone ALAD ALA. Male CD rats received a single ip injection Ga2(SO4)3 at doses 12.5, 25, 50, 100, 200 mg Ga/kg. A dose-dependent observed 24 hr later liver, kidney, erythrocytes. After 25 Ga/kg, maximal (42 49% control) occurred between 6 liver kidney full recovery activity 96 hr. In erythrocytes, (48% 48 Mild moderate renal proximal tubular necrosis pars recta after 100 mg/kg, but no histopathologic changes were evident lower doses. No consistent ALA observed. Lineweaver-Burk analyses hepatic activities absence presence indicated that by this element is noncompetitive (same Km, decreased Vmax). Gallium possess an constant (Ki) approximately 3 microns for ALAD, similar Ki obtained lead other studies. Incubation vitro lead, active thiol group inhibitor, resulted greater enzyme. Further studies demonstrated attenuation zinc, suggesting mechanism action may involve competition or displacement zinc from sulfhydryl enzyme site. Since which evident, determination various tissues, including blood, be potential value biomarker exposure/toxicity metals such gallium. The effect form route effects Group III on discussed.(ABSTRACT TRUNCATED AT 250 WORDS)