Abstract
Event Abstract Back to Event Experimental study on the effects of 7-nitroindazol, selective inhibitor of neuronal nitric oxide synthase (nNOS), on some brain and hepatic biochemical parameters Vessela Vitcheva1*, Rumyana Simeonova1 and Mitka Mitcheva1 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 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. 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 Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vessela Vitcheva Rumyana Simeonova Mitka Mitcheva Google Vessela Vitcheva Rumyana Simeonova Mitka Mitcheva Google Scholar Vessela Vitcheva Rumyana Simeonova Mitka Mitcheva PubMed Vessela Vitcheva Rumyana Simeonova Mitka Mitcheva Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Highlights
Nitric oxide (NO) has been shown to be involved in multiple processes in the central nervous system, including the development of tolerance to centrally acting compounds such as opioids [10], psychostimulants [6], ethanol [18] etc
The role of NO in the processes of drug tolerance and dependence development has been elucidated by using selective inhibitors of neuronal nitric oxide synthase
Lue et al [10] demonstrated that 7- nitroindazole (7-NI) blocked the development of morphine tolerance in rat hippocampal slices and Uzbay et al [18] showed that the inhibitor alleviated the signs of ethanol withdrawal
Summary
Nitric oxide (NO) has been shown to be involved in multiple processes in the central nervous system, including the development of tolerance to centrally acting compounds such as opioids [10], psychostimulants [6], ethanol [18] etc. The role of NO in the processes of drug tolerance and dependence development has been elucidated by using selective inhibitors of neuronal nitric oxide synthase (nNOS). Several studies have indicated that 7-NI affects different physical processes and behaviors, related to drug abuse, such as tolerance, withdrawal, neurotoxicity, psychomotor stimulation and reward. In one of their studies Itzhak and Ali [6] proved that administration of 7-NI reduced the hyperactivity and attenuated the induction of behavioral sensitisation to cocaine and amphetamines. Its structure suggests that 7-NI might undergo metabolism in the liver and might be involved in drug interactions
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
