Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by δ-aminolevulinic acid

Malgorzata Karbownik, Russel J. Reiter, Joaquin J. Garcia, Dun Xian Tan, Wenbo Qi, Lucien C. Manchester

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

δ-Aminolevulinic acid, precursor of heme, accumulates in a number of organs, especially in the liver, of patients with acute intermittent porphyria. The potential protective effect of melatonin against oxidative damage to nuclear DNA and microsomal and mitochondrial membranes in rat liver, caused by δ-aminolevulinic acid, was examined. Changes in 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and alterations in membrane fluidity (the inverse of membrane rigidity) and lipid peroxidation in microsomal and mitochondrial membranes, as indices of damage to lipid and protein molecules in membranes, were estimated. Measurements were made in rat liver after a 2 week treatment with δ-aminolevulinic acid (40 mg/kg b.w., every other day). To test the potential protective effects of melatonin, the indole was injected (i.p. 10 mg/kg b.w.) 3 times daily for 2 weeks. 8-OHdG levels and lipid peroxidation in microsomal membranes increased significantly whereas microsomal and mitochondrial membrane fluidity decreased as a consequence of δ-aminolevulinic acid treatment. Melatonin completely counteracted the effects of δ-aminolevulinic acid. Melatonin was highly effective in protecting against oxidative damage to DNA as well as to microsomal and mitochondrial membranes in rat liver and it may be useful as a cotreatment in patients with acute intermittent porphyria. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)140-146
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1523
Issue number2-3
DOIs
StatePublished - Oct 18 2000

Keywords

  • DNA
  • Free radical
  • Melatonin
  • Membrane
  • Porphyria

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by δ-aminolevulinic acid'. Together they form a unique fingerprint.

Cite this