Experimental study on the effects of 7-nitroindazol, selective inhibitor of neuronal nitric oxide synthase (nNOS), on some brain and hepatic biochemical parameters
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1
Medical University, Department of Pharmacology, Pharmacotherapy and Toxicology, Bulgaria
7-nitroindazole (7-NI) is a selective nNOS inhibitor, which has been proved to have a beneficial effect on different physical processes and behaviors, related to drug abuse, such as tolerance, withdrawal, neurotoxicity and reward. However there are no information available for its toxicity and hepatic biotransformation. The objective of the following study was to investigate the effects of 7-NI on rat brain and liver, after multiple alone administartion. Male Wistar rats were treated with 7-NI (25 mg/kg i.p.) for 5 days. 24 hours after the last administration brains and livers were taken for biochemical assay. Being an inhibitor of nNOS, 7-NI significantly decreased the enzyme activity by 41%. For tracing the possible toxic effect of the compound, the quantity of malondialdehyde (MDA) and the level of reduced glutathion (GSH) were measured both in the brain and in the liver. Multiple administration of 7-NI did not affect the MDA quantity, neither in the brain, nor in the liver that corresponds with the literature data about the positive effect of 7-NI on lipid peroxidation. On the other hand, the GSH level was depleated by 43% in the brain and by 27% in the liver, which suggest a toxic effect of 7-NI. The chemical structure of 7-NI, benzpyrazole, which is a part of the structure of such substrates of cytochrome P 450 as antichelmintes, suggests hepatic metabolism of the compound. The cytochrome P 450 quantity and the activity of ethylmorphine-N-demethylase (EMND) and anilinehydroxilase (AH), were also assessed. 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.
Keywords:
7-nitroindazole,
nNOS inhibitor,
Brain,
Liver
Conference:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.
Presentation Type:
Oral
Topic:
Xenobiotic toxicity
Citation:
Vitcheva
V,
Simeonova
R and
Mitcheva
M
(2010). Experimental study on the effects of 7-nitroindazol, selective inhibitor of neuronal nitric oxide synthase (nNOS), on some brain and hepatic biochemical parameters.
Front. Pharmacol.
Conference Abstract:
8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010.
doi: 10.3389/conf.fphar.2010.60.00213
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Received:
28 Oct 2010;
Published Online:
04 Nov 2010.
*
Correspondence:
Dr. Vessela Vitcheva, Medical University, Department of Pharmacology, Pharmacotherapy and Toxicology, Sofia, Bulgaria, vesselavitcheva@yahoo.com