EXPERIMENTAL STUDY ON THE EFFECTS OF
7-NITROINDAZOL, A SELECTIVE INHIBITOR
OF NEURONAL NITRIC OXIDE SYNTHASE
(nNOS), ON SOME BRAIN AND HEPATIC
BIOCHEMICAL PARAMETERS
VESSELA VITCHEVA*, RUMYANA SIMEONOVA, MITKA
MITCHEVA
Laboratory of “Drug metabolism and drug toxicity”, Department of
“Pharmacology, Pharmacotherapy and Toxicology”, Faculty of
Pharmacy; 2 “Dunav” st, Sofia – 1000, Bulgaria
*corresponding author: vesselavitcheva@yahoo.com
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Abstract:

The objective of the present study was to investigate the effects of selective
neuronal nitric oxide inhibitor 7- nitroindazole (7-NI) on rat brain and liver, after multiple administrations. Male Wistar rats were treated with 7-NI (25 mg/kg b.w. i.p.) for 5 days. 24 hours after the last administration brains and livers were processed for the biochemical assay. Being an inhibitor of neuronal nitric oxide synthase (nNOS), 7-NI significantly
decreased the enzyme activity by 41%.
The production of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) levels both in liver and brain were measured to assess a possible toxic effect of the compound. Multiple administration of 7-NI did not affect the TBARS levels, neither in the brain, nor in the liver but GSH levels were depleated in both tissues, which suggests a toxic effect of 7-NI. The cytochrome P 450 quantity and the activity of ethylmorphine-N-demethylase (EMND) and anilinehydroxilase (AH), were also measured.
7-NI decreased P 450 quantity by 30 % and AH activity by 26 %. At the same time EMND activity remained unchanged.
On the basis of these results we proved a hepatic metabolism of 7-NI that might be responsible for the detected GSH depletion in the liver and could be regarded as a precondition for hepatic drug interactions.

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