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

• Published in: Biochimica et biophysica acta Vol. 1523; no. 2-3; pp. 140 - 146
• Main Authors: Karbownik, Małgorzata, Reiter, Russel J., Garcia, Joaquin J., Tan, Dun Xian, Qi, Wenbo, Manchester, Lucien C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 18.10.2000
• Subjects: Aminolevulinic Acid - toxicity; Animals; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; DNA; DNA Damage; Free radical; Intracellular Membranes - drug effects; Intracellular Membranes - physiology; Lipid Peroxidation - drug effects; Liver - drug effects; Liver - pathology; Liver - physiology; Male; Melatonin; Melatonin - pharmacology; Membrane; Membrane Fluidity - drug effects; Microsomes, Liver - drug effects; Microsomes, Liver - physiology; Mitochondria, Liver - drug effects; Mitochondria, Liver - physiology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Porphyria; Rats; Rats, Sprague-Dawley; Porphyria; Membrane; Melatonin; DNA; Free radical
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/S0304-4165(00)00110-0

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.