In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes
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...
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1998
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v24_n1_p1_Princ http://hdl.handle.net/20.500.12110/paper_07423098_v24_n1_p1_Princ |
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paper:paper_07423098_v24_n1_p1_Princ2023-06-08T15:44:42Z In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes δ-aminolevulinate dehydratase δ-aminolevulinic acid Antioxidative enzymes Melatonin Porphobilinogen deaminase Reactive oxygen species aminolevulinic acid antioxidant melatonin porphobilinogen deaminase porphobilinogen synthase animal experiment animal tissue article brain cortex brain injury cerebellum controlled study intraperitoneal drug administration lipid peroxidation male neuroprotection nonhuman oxidative stress rat Aminolevulinic Acid Animals Antioxidants Cerebellum Cerebral Cortex Free Radical Scavengers Hydroxymethylbilane Synthase Injections, Intraperitoneal Lipid Peroxidation Male Malondialdehyde Melatonin Oxidative Stress Porphobilinogen Synthase Rats Reactive Oxygen Species 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. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v24_n1_p1_Princ http://hdl.handle.net/20.500.12110/paper_07423098_v24_n1_p1_Princ |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
δ-aminolevulinate dehydratase δ-aminolevulinic acid Antioxidative enzymes Melatonin Porphobilinogen deaminase Reactive oxygen species aminolevulinic acid antioxidant melatonin porphobilinogen deaminase porphobilinogen synthase animal experiment animal tissue article brain cortex brain injury cerebellum controlled study intraperitoneal drug administration lipid peroxidation male neuroprotection nonhuman oxidative stress rat Aminolevulinic Acid Animals Antioxidants Cerebellum Cerebral Cortex Free Radical Scavengers Hydroxymethylbilane Synthase Injections, Intraperitoneal Lipid Peroxidation Male Malondialdehyde Melatonin Oxidative Stress Porphobilinogen Synthase Rats Reactive Oxygen Species |
| spellingShingle |
δ-aminolevulinate dehydratase δ-aminolevulinic acid Antioxidative enzymes Melatonin Porphobilinogen deaminase Reactive oxygen species aminolevulinic acid antioxidant melatonin porphobilinogen deaminase porphobilinogen synthase animal experiment animal tissue article brain cortex brain injury cerebellum controlled study intraperitoneal drug administration lipid peroxidation male neuroprotection nonhuman oxidative stress rat Aminolevulinic Acid Animals Antioxidants Cerebellum Cerebral Cortex Free Radical Scavengers Hydroxymethylbilane Synthase Injections, Intraperitoneal Lipid Peroxidation Male Malondialdehyde Melatonin Oxidative Stress Porphobilinogen Synthase Rats Reactive Oxygen Species In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| topic_facet |
δ-aminolevulinate dehydratase δ-aminolevulinic acid Antioxidative enzymes Melatonin Porphobilinogen deaminase Reactive oxygen species aminolevulinic acid antioxidant melatonin porphobilinogen deaminase porphobilinogen synthase animal experiment animal tissue article brain cortex brain injury cerebellum controlled study intraperitoneal drug administration lipid peroxidation male neuroprotection nonhuman oxidative stress rat Aminolevulinic Acid Animals Antioxidants Cerebellum Cerebral Cortex Free Radical Scavengers Hydroxymethylbilane Synthase Injections, Intraperitoneal Lipid Peroxidation Male Malondialdehyde Melatonin Oxidative Stress Porphobilinogen Synthase Rats Reactive Oxygen Species |
| description |
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. |
| title |
In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| title_short |
In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| title_full |
In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| title_fullStr |
In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| title_full_unstemmed |
In vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| title_sort |
in vivo protection by melatonin against δ-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes |
| publishDate |
1998 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_07423098_v24_n1_p1_Princ http://hdl.handle.net/20.500.12110/paper_07423098_v24_n1_p1_Princ |
| _version_ |
1768545055429099520 |