Melatonin reduces the oxidation of nuclear DNA and membrane lipids induced by the carcinogen delta-aminolevulinic acid.
Well known are the anti-oxidant, free radical-scavenging and anti-tumorigenic properties of melatonin. delta-Aminolevulinic acid (ALA) is a precursor of heme synthesis. When over-produced and accumulated in tissues, ALA is a potential carcinogen, such as in the course of acute intermittent porphyria, hereditary tyrosinemia and lead poisoning. Our aim was to examine the potential protective effect of melatonin against oxidative damage to nuclear DNA and membrane lipids in rat lung and spleen caused by ALA. Changes in 8-hydroxy-2;-deoxyguanosine (8-OHdG) levels, an index of DNA damage, and the level of malondialdehyde + 4-hydroxyalkenals, an index of lipid peroxidation, were measured. Rats were injected with ALA (i.p., 40 mg/kg body weight, every other day) and/or with melatonin (i.p., 10 mg/kg body weight, 3 times daily) for 2 weeks. Both 8-OHdG and lipid peroxidation levels increased significantly in lung and spleen due to ALA treatment. Co-treatment with melatonin completely counteracted the effects of ALA. In conclusion, melatonin effectively protects nuclear DNA and lipids in rat lung and spleen against oxidative damage caused by the carcinogen ALA, and the indole may be of value as a supplement in patients suffering from molecular damage related to ALA accumulation.
Karbownik
M
M
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Tan
D X
DX
Reiter
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000622:Aminolevulinic Acid / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D008563:Membrane Lipids / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D002273:Carcinogens; D008563:Membrane Lipids; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D008550:Melatonin