Involvement of nitric oxide in nigrostriatal dopaminergic system degeneration: a neurochemical study .
The present study was undertaken to explore the involvement of nitric oxide (NO) in the 6-hydroxydopamine (6-OHDA) experimental model of Parkinson's disease (PD) in rats. The effect of pharmacological manipulation of the NO system was evaluated on striatal dopamine (DA) level decrease produced by the toxin. 7-nitroindazole (7-NI, 50 mg/kg i.p.; n= 5) pretreatment significantly restored the striatal DA contents. Conversely, 40 mg/kg i.p. of molsidomine (MOL, n= 5), an NO donor, significantly worsened the neurodegeneration (n= 5) and completely counteracted the neuroprotective effect of 7-NI (n= 5). Thus, a crucial role for NO in 6-OHDA induced neurodegeneration is suggested together with a protective benefit for inhibitors of NOS in the treatment of PD.
Di Matteo
Vincenzo
V
Instituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro (Chieti), Italy.
Pierucci
Massimo
M
Benigno
Arcangelo
A
Crescimanno
Giuseppe
G
Esposito
Ennio
E
Di Giovanni
Giuseppe
G
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors; D016627:Oxidopamine / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D007191:Indazoles; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D016627:Oxidopamine; D008981:Molsidomine; C080122:7-nitroindazole