Melatonin reduces rat hepatic macromolecular damage due to oxidative stress caused by delta-aminolevulinic acid.
Delta-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 delta-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 delta-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 delta-aminolevulinic acid treatment. Melatonin completely counteracted the effects of delta-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.
Karbownik
M
M
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
Reiter
R J
RJ
Garcia
J J
JJ
Tan
D X
DX
Qi
W
W
Manchester
L C
LC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000622:Aminolevulinic Acid / Q000633:toxicity*; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D008560:Membrane Fluidity / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000622:Aminolevulinic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin