Bilirubin is highly effective in preventing in vivo delta-aminolevulinic acid-induced oxidative cell damage

Biochim Biophys Acta. 2003 Jul 14;1638(2):173-8. doi: 10.1016/s0925-4439(03)00081-4.


Delta-aminolevulinic acid (ALA), precursor of heme, accumulates in a number of organs, particularly in liver of patients with acute porphyrias or lead intoxication. This study characterizes the involvement of bilirubin as an antioxidant in a chronic intoxication with ALA. Female Wistar rats were injected intraperitoneally a daily dose of 40 mg ALA/body wt., during 10 days. A marked increase in lipid peroxidation and a decrease in GSH content were observed 24 h after the last injection of ALA. The activities of liver antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase were also diminished. ALA synthase (ALA-S) and heme oxygenase-1 were induced. Both ALA dehydratase (ALA-D) and porphobilinogenase (PBG-ase) activities were inhibited. Administration of bilirubin (5 mmol/kg body wt.) 2 h before ALA treatment entirely prevented the effects of ALA. Co-administration of ALA and Sn-protoporphyrin IX (Sn-PPIX; 100 microg/body wt., i.p.), a potent inhibitor of heme oxygenase, completely abolished its induction and provoked a marked decrease in liver GSH levels as well as an increase in lipid peroxidation. These results add further support to the proposal assigning bilirubin a key protective role against oxidative damage here induced by ALA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Aminolevulinate Synthetase / metabolism
  • Aminolevulinic Acid / toxicity*
  • Ammonia-Lyases / antagonists & inhibitors
  • Animals
  • Antioxidants / pharmacology*
  • Bilirubin / administration & dosage
  • Bilirubin / pharmacology*
  • Catalase / metabolism
  • Enzyme Induction
  • Female
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Heme Oxygenase (Decyclizing) / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / enzymology
  • Oxidative Stress / drug effects*
  • Porphobilinogen Synthase / antagonists & inhibitors
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism


  • Antioxidants
  • Aminolevulinic Acid
  • Catalase
  • Glutathione Peroxidase
  • Heme Oxygenase (Decyclizing)
  • Superoxide Dismutase
  • 5-Aminolevulinate Synthetase
  • Porphobilinogen Synthase
  • Ammonia-Lyases
  • porphobilinogenase
  • Glutathione
  • Bilirubin