Melatonin protects against oxidative stress caused by 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Melatonin protects against oxidative stress caused by 1-methyl-
4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum
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| Creator |
Thomas, Bobby
Mohanakumar , K P |
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| Subject |
Cell Biology & Physiology
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| Description |
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 e.ect 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 signi.cant 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 signi.cant depletion of GSH, and increased the speci.c 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 e.ect 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.
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| Date |
2004
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/439/1/JOURNAL_OF_PINEAL_RESEARCH%2C_36(_1)%2C_25%2D32[97].pdf
Thomas, Bobby and Mohanakumar , K P (2004) Melatonin protects against oxidative stress caused by 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine in the mouse nigrostriatum. J. Pineal Res. , 36 (1). pp. 25-32. |
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| Relation |
http://dx.doi.org/10.1046/j.1600-079X.2003.00096.x
http://www.eprints.iicb.res.in/439/ |
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