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Neuroprotective role of PDE4 and PDE5 inhibitors in 3-nitropropionic acid induced behavioral and biochemical toxicities in rats.

Abstract：

:Phosphodiesterase inhibitors have been reported to be beneficial in cognitive and motor disorders. In the present study, we have investigated the effects of RO 20-1724 (PDE4 inhibitor) and sildenafil (PDE5 inhibitor) in 3-nitropropionic acid (3-NP) induced experimental Huntington's disease in rats. 3-Nitropropionic acid was administered for 14 days (10 mg/kg i.p.) 1h following 3-NP administration, the rats were treated with either vehicle, RO 20-1724 (0.25 and 0.5 mg/kg i.p.) or sildenafil (2 and 4 mg/kg i.p.) for 14 days. Cognitive functions were assessed by using Morris water maze whereas, motor functions were assessed by spontaneous locomotor activity, limb withdrawal and suspended wire test at different time points. Biochemically, markers of oxidative stress and cell damage, such as reduced glutathione, malondialdehyde, nitrite and lactate dehydrogenase levels were assessed terminally in the brain homogenate. Chronic administration of 3-NP produced significant decrease in body weight, showed marked abnormalities in cognitive and motor functions. Further, significant oxidative-nitrosative stress and cell damage was also observed. Chronic administration of RO 20-1724 and sildenafil in 3-NP treated rats significantly and dose dependently attenuated 3-NP induced behavioral and biochemical abnormalities in rats. Both these drugs were equally effective in attenuating 3-NP induced neurotoxicity. These results suggesting that the inhibition of PDE4 and PDE5 would be therapeutic in neurodegenerative disorders associated with cognitive and motor dysfunction.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Thakur T,Sharma S,Kumar K,Deshmukh R,Sharma PL

doi

10.1016/j.ejphar.2013.06.035

subject

Has Abstract

pub_date

2013-08-15 00:00:00

pages

515-21

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(13)00504-9

journal_volume

714

pub_type

杂志文章

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