Alteration of mitochondrial structure and heme biosynthetic parameters in liver and kidney cells by bismuth.
Ultrastructural and biochemical studies were conducted to evaluate the effects of bismuth, a potentially toxic group V trace metal, on organelle structure and heme biosynthetic parameters in rat liver and kidney cells. Bismuth subnitrate (BiONO3) was administered subcutaneously to male rats in 0, 20, 40, or 80 mg/kg doses 16 hr prior to euthanasia. Electron microscopy revealed swollen mitochondria and distortion of mitochondrial inner membranes in liver and renal proximal tubule cells at 40 and 80 mg/kg dose levels. In liver, dose-related decreases were observed in the activities of the mitochondrial enzymes, delta-aminolevulinic acid (ALA) synthetase and heme synthetase, and of the cytoplasmic enzyme, ALA dehydratase, to 51, 48, and 35% of levels seen in untreated controls, respectively. In kidney, ALA synthetase and ALA dehydratase, but not heme synthetase, were depressed in vivo to 32 and 20% of control, respectively. Studies in vitro conducted for 1-hr periods with Bi concentrations at 0, 0.1, 0.2, or 0.4 mM in reaction mixtures revealed that the direct action of the metal on membranal enzymes only partially accounts for the impairment of the activity of membranal enzymes. These studies demonstrate that the initial acute effects of bismuth in liver and kidney cells include distortion of mitochondrial membranes and direct inhibition of specific heme pathway enzymes. Both effects contribute to compromise of membrane-associated enzymatic functions. These findings are comparable to those previously reported of other trace metals with known toxicologic potential and may represent early events in bismuth-induced cell injury.
D000624:5-Aminolevulinate Synthetase / Q000032:analysis; D000818:Animals; D001729:Bismuth / Q000633:toxicity*; D006418:Heme / Q000096:biosynthesis*; D011163:Hydroxymethylbilane Synthase / Q000032:analysis; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D000623:Porphobilinogen Synthase / Q000032:analysis; D051381:Rats
D006418:Heme; D000624:5-Aminolevulinate Synthetase; D011163:Hydroxymethylbilane Synthase; D000623:Porphobilinogen Synthase; D001729:Bismuth