Vol. 9, No 2, 2002 pp. 162 - 165
UC 616.851
EFFECTS OF NITRIC OXIDE SYNTHASE INHIBITORS,
7-NI AND L-NAME, ON CONTENT OF REDUCED GLUTATHIONE IN EXPERIMENTAL MODEL
HUNTINGTON'S DISEASE
Ivana Maksimović1,
Marina Jovanović1, Rosa Mihajlović2,
Miodrag Čolić1, Milica Ninković1,
Živorad Maličević1
1Military Medical
Academy - Institute for Medical Research, Belgrade, Serbia
2Institute for
Rehabilitation, Belgrade, Serbia
E-mail: maksi@infosky.net
Summary. The etiology of neuronal death in neurodegenerative diseases,
including Huntington?s disease (HD), is still unknown. There could be a
complex interplay between altered energy metabolism, excitotoxicity and
oxidative stress. Our aim was to examine the effects of intrastriatal injection
of a selective inhibitor of neuronal nitric oxide synthase, 7 nitro indazole
(7-NI), and non-specific potent nitric oxide synthase inhibitor, N?-nitro-l-arginine
methyl ester (l-NAME), to investigate the possible involvement of nitric
oxide in quinolinic acid (QA)-induced striatal toxicity in the rat. Unilateral
administration of QA in rat striatum in a single dose of 150 nM was used
as model of HD. The second and third group were treated with 7-NI and QA
and l-NAME and QA, respectively. The control group was treated with 0.9%
saline solution likewise. The content of reduced glutathione, a key antioxidant,
was increased in the hippocampus and basal forebrain of 7-NI- and QA-treated
animals, compared to the QA-treated animals. These results support the
hypothesis that oxygen free radicals contribute to the excitotoxic neuronal
injury, and also that neuronal nitric oxide synthase inhibitor 7-NI, but
not l-NAME could be potential neuroprotective agents in HD.
Key words: Huntington's disease, quinolinic acid, N?-nitro-l-arginine
methyl estar, 7-nitro indazole,
reduced glutathione
UTICAJ INHIBITORA SINTAZE AZOTNOG OKSIDA,
7-NI I L-NAME
NA SADRŽAJ REDUKOVANOG GLUTATJONA U EKSPERIMENTALNOM
MODELU HANTINGTONOVE BOLESTI
Kratak sadržaj: Etiologija selektivnog umiranja neurona u neurodegenerativnim
bolestima je nepoznata, iako postoje dokazi o defektu energetskog metabolizma,
ekscitotoksičnosti i oksidativnom oštećenju. Verovatno je da ključnu ulogu
ima kompleksna interakcija između ovih mehanizama. Cilj našega rada bio
je da se ispitaju efekti intrastrijatne primene selektivnog inhibitora
neuronske azot oksid sintaze-7 nitro indazola (7-NI), kao i nespecifičnog
inhibitora azot oksid sintaze-N?-nitro-l-arginin metil estra (l-NAME),
zbog moguće uključenosti azot oksida u toksičnost strijatuma izazvanu hinolinskom
kiselinom (HK), kod pacova. Unilateralna aplikacija HK u strijatum pacova
u pojedinačnoj dozi od 150 nM korišćena je kao model HB. Druga i treća
grupa tretirane su 7-NI i HK, odnosno l-NAME i HK. Kontrolna grupa dobijala
je 0.9% fiziološki rastvor na isti način. Sadržaj redukovanog glutationa,
ključnog antioksidanta, povećan je u hipokampusu i bazalnom prednjem mozgu
životinja tretiranih 7-NI i HK, u poređenju sa životinjama tretiranim samo
HK. Ovi podaci pokazuju da kiseonični slobodni radikali učestvuju u ekscitotoksičnom
oštećenju neurona, kao i da inhibitor neuronske azot oksid sintaze 7-NI,
za razliku od l-NAME, može biti potencijalni neuroprotektivni agens u HB.
Ključne reči: Hantingtonova bolest, hinolinska kiselina,
N?-nitro-l-arginin metil estar, 7-nitro indazol,
redukovani glutation
