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 o rgans, especially in the liver, of patients with acute intermittent porphyr ia. The potential protective effect of melatonin against oxidative damage t o nuclear DNA and microsomal and mitochondrial membranes in rat liver, caus ed by delta -aminolevulinic acid, was examined. Changes in 8-hydroxy-2'-deo xyguanosine (8-OHdG) levels, an index of DNA damage, and alterations in mem brane 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 r at 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 melato nin, 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 si gnificantly whereas microsomal and mitochondrial membrane fluidity decrease d as a consequence of delta -aminolevulinic acid treatment. Melatonin compl etely counteracted the effects of 6-aminolevulinic acid. Melatonin was high ly effective in protecting against oxidative damage to DNA as well as to mi crosomal and mitochondrial membranes in rat liver and it may be useful as a cotreatment in patients with acute intermittent porphyria. (C) 2000 Elsevi er Science B.V. All rights reserved.