Dosing-Time Dependence of Lethal Toxicity Induced by Nitroprusside in Young Mice
- *Corresponding Author:
- Mamane Sani
Department of Biology, Faculty of Sciences of Maradi
University of Maradi, BP 465 Maradi, Niger
Tel: + (227) 20-41-01-32
Fax: + (227) 20-41-01-33
E-mail: [email protected]
Received Date: November 23, 2011; Accepted Date: December 14, 2011; Published Date: December 21, 2011
Citation: Sani M, Sebai H, Boughattas NA, Ben-Attia M (2011) Dosing-Time Dependence of Lethal Toxicity Induced by Nitroprusside in Young Mice. J Clinic Toxicol 1:114. doi: 10.4172/2161-0495.1000114
Copyright: © 2011 Sani M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sodium nitroprusside (SNP) is a potent vasodilator and is commonly used as an antihypertensive agent in postoperative cardiac surgical patients. In this study, we investigated whether the SNP-induced lethality is influenced by the dosing-time. Mortality was induced by administering SNP in different doses (4.9, 5.4, 6.0, 6.6 mg/kg, i.p.) to Swiss albino mice, 2 to 8 weeks old, synchronized for at least 2 weeks by 12 h light (rest)/12 h dark (activity) span. Each dose was administered to comparable groups of animals (n= 6) at six different circadian times: 1, 5, 9, 13, 17, and 21 hours after light onset (HALO). Both ?2 and cosinor methods were used to analyze the time series data. Statistically significant dosing time-dependent changes were validated in the daily scale with the males more sensitive than females. A ultradian (? = 12 h) rhythm was detected by cosinor (P < 0.002) for each of the three administered doses (4.9, 5.4, 6.0 mg/kg) in 2 week old mice of both genders. Moreover, in addition to the ultradian rhythm, a significant (P < 0.004) circadian (? = 24 h) component had been detected in 6 mg/kg SNP-treated male mice. However, there was only a circadian rhythm detected in 4 and 8 weeks old mice after acute SNP (6.0, 6.6 mg/kg) treatment, with peak time located at ? 21 and ? 17 HALO, respectively. In conclusion, tolerance to nitroprusside varies not only according to the circadian time but also according to the dose, age, and gender of animal.