Tags

Type your tag names separated by a space and hit enter

Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum.
J Pineal Res. 2004 Jan; 36(1):25-32.JP

Abstract

We tested the hypothesis that melatonin acts as a powerful hydroxyl radical (*OH) scavenger in vivo in the brain, and interferes with oxidative stress caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We investigated the effect of melatonin on in vitro *OH production employing a Fenton-like reaction in test tubes, and ex vivo *OH generation in isolated mitochondria induced by 1-methyl-4-phenyl pyridinium (MPP+), as well as on in vivo *OH formation in the mouse striatum following systemic administration of MPTP. We also measured reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity in the nucleus caudatus putamen (NCP) and substantia nigra (SN), 7 days following MPTP and/or melatonin administration. Melatonin caused a significant and dose-dependent inhibition of the production of *OH in the in vitro, ex vivo and in vivo experimental conditions. Melatonin caused no changes in monoamine oxidase-B activity, in vitro in mitochondrial P2 fractions or in vivo following systemic administration. MPTP treatment in mice caused a significant depletion of GSH, and increased the specific activity of SOD both in SN and NCP on the seventh day. MPTP-induced GSH depletion was dose-dependently blocked in SN and NCP by melatonin. Higher doses of melatonin exhibited a synergistic effect on MPTP-induced increase in the SOD activity in the SN. These results suggest that while GSH inhibition is a direct consequence of *OH generation following neurotoxin administration, the increase in SOD activity is a compensatory mechanism for removing superoxide radicals generated as the result of MPTP. Our results not only point to the potency of melatonin in blocking the primary insults caused by MPTP, but also provide evidence for triggering secondary neuroprotective mechanisms, suggesting its use as a therapeutic agent in neurodegenerative disorders, such as Parkinson's disease.

Authors+Show Affiliations

Thomas B
Indian Institute of Chemical Biology, Division of Neurosciences, Calcutta, India.
Mohanakumar KP
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-Methyl-4-phenylpyridiniumAnimalsCell-Free SystemDopamine AgentsDose-Response Relationship, DrugFree Radical ScavengersGlutathioneHydrogen PeroxideHydroxyl RadicalIronMelatoninMiceMice, Inbred BALB CMitochondriaOxidative StressSubstantia NigraSuperoxide Dismutase

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14675127

Citation

Thomas, Bobby, and Kochupurackal P. Mohanakumar. "Melatonin Protects Against Oxidative Stress Caused By 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the Mouse Nigrostriatum." Journal of Pineal Research, vol. 36, no. 1, 2004, pp. 25-32.
Thomas B, Mohanakumar KP. Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J Pineal Res. 2004;36(1):25-32.
Thomas, B., & Mohanakumar, K. P. (2004). Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. Journal of Pineal Research, 36(1), 25-32.
Thomas B, Mohanakumar KP. Melatonin Protects Against Oxidative Stress Caused By 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the Mouse Nigrostriatum. J Pineal Res. 2004;36(1):25-32. PubMed PMID: 14675127.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin protects against oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. AU - Thomas,Bobby, AU - Mohanakumar,Kochupurackal P, PY - 2003/12/17/pubmed PY - 2004/9/24/medline PY - 2003/12/17/entrez SP - 25 EP - 32 JF - Journal of pineal research JO - J Pineal Res VL - 36 IS - 1 N2 - We tested the hypothesis that melatonin acts as a powerful hydroxyl radical (*OH) scavenger in vivo in the brain, and interferes with oxidative stress caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We investigated the effect of melatonin on in vitro *OH production employing a Fenton-like reaction in test tubes, and ex vivo *OH generation in isolated mitochondria induced by 1-methyl-4-phenyl pyridinium (MPP+), as well as on in vivo *OH formation in the mouse striatum following systemic administration of MPTP. We also measured reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity in the nucleus caudatus putamen (NCP) and substantia nigra (SN), 7 days following MPTP and/or melatonin administration. Melatonin caused a significant and dose-dependent inhibition of the production of *OH in the in vitro, ex vivo and in vivo experimental conditions. Melatonin caused no changes in monoamine oxidase-B activity, in vitro in mitochondrial P2 fractions or in vivo following systemic administration. MPTP treatment in mice caused a significant depletion of GSH, and increased the specific activity of SOD both in SN and NCP on the seventh day. MPTP-induced GSH depletion was dose-dependently blocked in SN and NCP by melatonin. Higher doses of melatonin exhibited a synergistic effect on MPTP-induced increase in the SOD activity in the SN. These results suggest that while GSH inhibition is a direct consequence of *OH generation following neurotoxin administration, the increase in SOD activity is a compensatory mechanism for removing superoxide radicals generated as the result of MPTP. Our results not only point to the potency of melatonin in blocking the primary insults caused by MPTP, but also provide evidence for triggering secondary neuroprotective mechanisms, suggesting its use as a therapeutic agent in neurodegenerative disorders, such as Parkinson's disease. SN - 0742-3098 UR - https://www.unboundmedicine.com/medline/citation/14675127/Melatonin_protects_against_oxidative_stress_caused_by_1_methyl_4_phenyl_1236_tetrahydropyridine_in_the_mouse_nigrostriatum_ DB - PRIME DP - Unbound Medicine ER -