Renal toxicity of the carcinogen delta-aminolevulinic acid: antioxidant effects of melatonin.
An increased incidence of cancer in patients suffering from acute intermittent porphyria (AIP) is thought to be related to delta-aminolevulinic acid (ALA) accumulation. Chronic treatment with ALA augmented 8-oxo-7,8-dihydro-2'-deoxyguanosine levels, decreased microsomal and mitochondrial membrane fluidity and increased lipid peroxidation in blood serum. Co-treatment with melatonin completely counteracted the effects of ALA. Melatonin effectively protects DNA and microsomal and mitochondrial membranes in rat kidney from oxidative damage due to ALA. Because of its low toxicity and anticarcinogenic properties, melatonin could be tested as an agent to reduce oxidative damage in patients with AIP.
Karbownik
M
M
Department of Cellular and Structural Biology, University of Texas Health Science Center, Mail Code 7762, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.
Tan
D
D
Manchester
L C
LC
Reiter
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000622:Aminolevulinic Acid / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000493:pharmacokinetics / Q000633:toxicity*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007425:Intracellular Membranes / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002273:Carcinogens; D008315:Malondialdehyde; D000622:Aminolevulinic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine; D008550:Melatonin