Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Evidence for Hydroxyl Radical Scavenging Action
of Nitric Oxide Donors in the Protection Against
1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats
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| Creator |
Banerjee, Rebecca
Saravanan, Karuppagounder S Thomas, Bobby Sindhu, Kizhake M Mohanakumar , K P |
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| Subject |
Cell Biology & Physiology
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| Description |
In the present study we provide evidence for
hydroxyl radical (•OH) scavenging action of nitric oxide
(NO•), and subsequent dopaminergic neuroprotection in
a hemiparkinsonian rat model. Reactive oxygen species
are strongly implicated in the nigrostriatal dopaminergic
neurotoxicity caused by the parkinsonian neurotoxin,
1-methyl-4-phenylpyridinium (MPP+). Since the role of this
free radical as a neurotoxicant or neuroprotectant is debatable,
we investigated the effects of some of the NO• donors
such as S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine
hydrochloride (SIN-1), sodium nitroprusside
(SNP) and nitroglycerin (NG) on in vitro •OH
generation in a Fenton-like reaction involving ferrous citrate,
as well as in MPP+-induced •OH production in the
mitochondria. We also tested whether co-administration of
NO• donor and MPP+ could protect against MPP+-induced
dopaminergic neurotoxicity in rats. While NG, SNAP and
SIN-1 attenuated MPP+-induced •OH generation in the mitochondria, and in a Fenton-like reaction, SNP caused up
to 18-fold increase in •OH production in the latter reaction.
Striatal dopaminergic depletion following intranigral infusion
of MPP+ in rats was significantly attenuated by NG,
SNAP and SIN-1, but not by SNP. Solutions of NG, SNAP
and SIN-1, exposed to air for 48 h to remove NO•, when
administered similarly failed to attenuate MPP+-induced
neurotoxicity in vivo. Conversely, long-time air-exposed
SNP solution when administered in rats intranigrally,
caused a dose-dependent depletion of the striatal dopamine.
These results confirm the involvement of •OH in the
nigrostriatal degeneration caused by MPP+, indicate the
•OH scavenging ability of NO•, and demonstrate protection
by NO• donors against MPP+-induced dopaminergic
neurotoxicity in rats.
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| Date |
2008
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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/197/1/NEUROCHEMICAL_RESEARCH%2C_33(_6)%2C985%2D995%2C2008[77].pdf
Banerjee, Rebecca and Saravanan, Karuppagounder S and Thomas, Bobby and Sindhu, Kizhake M and Mohanakumar , K P (2008) Evidence for Hydroxyl Radical Scavenging Action of Nitric Oxide Donors in the Protection Against 1-Methyl-4-phenylpyridinium-induced Neurotoxicity in Rats. Neurochem Res, 33 (6). pp. 985-995. |
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| Relation |
http://dx.doi.org/10.1007/s11064-007-9473-z
http://www.eprints.iicb.res.in/197/ |
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