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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. Rezumat Lucrarea prezinta studii experimentale privind efectele 7-nitroindazolului (7-NI), un inhibitor selectiv al biosintezei oxidului nitric la nivelul ţesuturilor cerebrale si hepatice, provenite de la sobolani. Au fost evaluate atât concentraţia TBARS (thiobarbituric acid reactive substances) cât si concentraţia glutationului total. A fost evaluat cantitativ citocromul P450, precum si activitatea enzimatică a etilmorfin-N-demetilazei (EMND) si a anilinhidroxilazei (AH).

frontiers in pharmacology

Experimental study on the effects of 7-nitroindazol, selective inhibitor of neuronal nitric oxide synthase (nNOS), on some brain and hepatic biochemical parameters