The Possible Role of Nitric Oxide Pathway in Pentylenetetrazole Preconditioning Against Seizure in Mice
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Preconditioning is defined as an induction of adaptive response in organs against lethal stimulation provoked by subsequent mild sublethal stress. Several chemical agents have been demonstrated to cause brain tolerance through preconditioning. The aim of the present study is to test the hypothesis that preconditioning with pentylenetetrazole (PTZ) may have protective effect against seizure induced by i.v. infusion of PTZ. Mice were preconditioned by low-dose administration of PTZ (25 mg/kg) for 5 consecutive days, and the threshold of seizure elicited by i.v. infusion of PTZ was measured. To investigate the possible role of nitric oxide, NOS inhibitor enzymes, including L-NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) (10 mg/kg), aminoguanidine (AG) (50 mg/kg), 7-nitroindazole (7-NI) (15 mg/kg), and L-arginine (L-arg) (60 mg/kg), were administered concomitantly with PTZ in both acute and chronic phases. Determination of seizure threshold revealed significant enhancement after preconditioning with low dose of PTZ. While the protective effect of PTZ preconditioning was enhanced after the administration of L-arg, it was reversed following administration of L-NAME and 7NI, suggesting the involvement of nitric oxide pathway as an underlying mechanism of PTZ-induced preconditioning. Preconditioning with PTZ led to brain tolerance and adaptive response in animal model of PTZ-induced seizure. This effect is in part due to the involvement of nitric oxide pathway.
KeywordsPentylenetetrazole Preconditioning Nitric oxide Seizure Mice
This study was funded and supported by Experimental Medicine Research Center, Tehran University of Medical Sciences (http://tums.ac.ir/?lang=en), grant no. 97-01-158-37318 to AD, and a grant (96002757) from Iran National Science Foundation (INSF).
Compliance with Ethical Standards
All applicable international and institutional guidelines for the care and use of animals were followed.
Conflict of Interest
The authors declare that they have no conflict of interest.
- Barone FC, White RF, Spera PA, Ellison J, Currie RW, Wang X, Feuerstein GZ (1998) Ischemic preconditioning and brain tolerance: temporal histological and functional outcomes, protein synthesis requirement, and interleukin-1 receptor antagonist and early gene expression. Stroke 29(9):1937–1951PubMedGoogle Scholar
- Dahl NA, Balfour WM (1964) Prolonged anoxic survival due to anoxia pre-exposure: brain ATP, lactate, and pyruvate. Am J Phys 207(2):452–456Google Scholar
- Kume M, Yamamoto Y, Saad S, Gomi T, Kimoto S, Shimabukuro T, Yagi T, Nakagami M, Takada Y, Morimoto T, Yamaoka Y (1996) Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemia-reperfusion injury. J Lab Clin Med 128(3):251–258PubMedGoogle Scholar
- Maulik N, Engelman RM, Wei Z, Liu X, Rousou JA, Flack JE, Deaton DW, Das DK (1995) Drug-induced heat-shock preconditioning improves postischemic ventricular recovery after cardiopulmonary bypass. Circulation 92(9):381–388Google Scholar
- Meller R, Cameron JA, Torrey DJ, Clayton CE, Ordonez AN, Henshall DC, Minami M, Schindler CK, Saugstad JA, Simon RP (2006) Rapid degradation of Bim by the ubiquitin-proteasome pathway mediates short-term ischemic tolerance in cultured neurons. J Biol Chem 281(11):7429–7436PubMedPubMedCentralGoogle Scholar
- National Research Council Committee for the Update of the Guide for the, C., Use of Laboratory, A (2011) The National Academies Collection: Reports funded by National Institutes of Health, in: th (Ed.) Guide for the Care and Use of Laboratory Animals. National Academies Press (US) National Academy of Sciences, Washington (DC)Google Scholar
- Neely CF, Keith IM (1995) A1 adenosine receptor antagonists block ischemia-reperfusion injury of the lung. Am J Physiol Lung Cell Mol Physiol 268(6):L1036–L1046Google Scholar
- Rauca C, Rüthrich H-L (1995) Moderate hypoxia reduces pentylenetetrazol-induced seizures. Naunyn Schmiedeberg's Arch Pharmacol 351(3):261–267Google Scholar
- Tsikas D (2007) Analysis of nitrite and nitrate in biological fluids by assays based on the Griess reaction: appraisal of the Griess reaction in the L-arginine/nitric oxide area of research. J Chromatogr B Anal Technol Biomed Life Sci 851(1–2):51–70Google Scholar