In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes
Article first published online: 30 JAN 2007
Journal of Pineal Research
Volume 24, Issue 1, pages 1–8, January 1998
How to Cite
Princ, F. G., Maxit, A. G., Cardalda, C., Batlle, A. and Ana Juknat, A. (1998), In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes. Journal of Pineal Research, 24: 1–8. doi: 10.1111/j.1600-079X.1998.tb00359.x
- Issue published online: 30 JAN 2007
- Article first published online: 30 JAN 2007
- May 28,1997; July 31,1997.
- reactive oxygen species;
- δ-aminolevulinic acid;
- porphobilinogen deaminase;
- 8-aminolevulinate dehydratase;
- antioxidative enzymes
Princ FG, Maxit AG, Cardalda C, Batlle A, Juknat AA. In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes. J. Pineal Res. 1998; 24:1–8. © Munksgaard, Copenhagen
Accumulation of 8-aminolevulinic acid (ALA), as it occurs in acute intermittent porphyria, is a potential endogenous source of reactive oxygen species (ROS) which can then produce oxidative damage to cell structures and macromolecules. This in vivo study investigated whether melatonin could prevent the deleterious effects of ALA. Rats were injected i.p. for 2 weeks with ALA (40 mg/kg on alternate days) and/or with melatonin (50 μg/kg or 500 μg/kg daily). Administration of pharmacological doses of melatonin reduced and/or prevented ALA-induced lipid peroxidation (LPO) in both cerebral cortex and cerebellum, providing further evidence of melatonin's action as a ROS scavenger. Administration of pharmacological concentrations of melatonin to ALA-injected rats showed the protective properties of melatonin on the activities of both porphobilinogen-deaminase and δ-aminolevulinate dehydratase (ALA-D) in the cerebral cortex; the effect on ALA-D activity was unexpectedly high (at least 6-fold), indicating that, besides acting as a scavenger of hydroxyl radicals, melatonin may exert its protection on ALA-D through other mechanisms, such as increasing mRNA levels of antioxidant enzymes or/ and inducing glutathione peroxidase activity. The possibility that changes in the expression of antioxidant enzymes could affect the expression of other proteins, even those not related to the cellular ROS homeostasis, should also not be discarded. The potential use of melatonin as an antioxidant and for its reactivating properties in the treatment of acute porphyrias is considered.