In vivo protection by melatonin against δ‐aminolevulinic acid‐induced oxidative damage and its antioxidant effect on the activity of haem enzymes

Abstract

Accumulation of delta-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 microg/kg or 500 microg/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 delta-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.

The Effects of Exogenous Melatonin on Peripheral Nerve Regeneration and Collagen Formation in Rats

“…The second effect is through the receptors over the genomes. Through these receptors, it induces enzymes that detoxify free radicals [10][11][12][13][14][15][16][17][18][19][20][21][22]. However, both the direct and indirect effects do not occur sufficiently at physiologic levels.…”

Immunohistochemical evidence for the presence of tryptophan hydroxylase and serotonin in the rodent Harderian gland

“…Exogenous melatonin administration has been demonstrated to reduce the area occupied by intraluminal porphyrin accretions (Rodriguez-Colunga et al 1991) and the expression of the aminolevulinate synthase (the rate-limiting enzyme for porphyrin synthesis) gene and leads to decrease porphyrin concentrations (Dubey and Haldar 1997) in the rodent Harderian gland. Recently, Princ et al (1998) and Carneiro and Reiter (1998) have shown that, in the brain, melatonin prevents the damage induced by free radicals generated by porphyrin metabolism. Ultrastructural observations suggest that porphyrins in the rat Harderian gland are selectively secreted by the type II cells (Djeridane 1994a).…”

Melatonin Prevents Chemical-Induced Haemopoietic Cell Death

“…In various experimental models of tissue damage, its protective role was reported by reducing oxidative stress and lipid peroxidation [6,7]. The ability of MEL to reduce radical production, increasing the activity of many antioxidant enzymes [8], has been demonstrated in oxidant-related pathological conditions, where radical species are measured in extracellular fluids [9,10]. …”