Sani Mamane, Sebai Hichem, Boughattas Naceur A, Ben-Attia Mossadok
Département de Biologie, Faculté des Sciences de Maradi, Université de Maradi, 465 Maradi, Niger.
J Circadian Rhythms. 2011 Jun 17;9(1):5. doi: 10.1186/1740-3391-9-5.
Sodium nitroprusside (SNP) is widely used in pharmacological studies as a potent vasodilator or a nitric oxide donor. SNP-induced ataxic effects were assessed in mice by the Joulou-Couvoisier test. Swiss albino mice of both genders, 2-8 weeks of age, were acclimated at least for 2 weeks to 12 h light (rest span)/12 h dark (activity span). In 2 and 4 week old mice, maxima of ataxia were found following intraperitoneal administration of a dose ranging from 3 to 3.6 mg.kg-1 SNP at ≈ 1 and 13 HALO (Hours After Light Onset). The sublethal toxicity was statistically dosing-time dependent (χ2 test: P < 0.005). No rhythm was validated in neurotoxicity by cosinor analyses. At the 8th week of post-natal development (PND), SNP-induced ataxia was greatest at ≈ 1 HALO (69% in males vs. 49% in females) and lowest at ≈ 13 HALO (21% in males vs. 11% in females) (χ2 test: P < 0.00001). Cosinor analysis also revealed no statistically significant rhythm in mice injected with 3 or 3.3 mg.kg-1. However, a significant circadian (τ = 24 h) rhythm was detected by adjusted cosinor in 3.6 mg.kg-1-treated mice (P < 0.004). In all studied groups, SNP-induced motor impairment (expressed in %) was lower during the dark than the light phase. Furthermore, there was a non-significant gender-related difference in SNP-induced neuronal toxicity with the males more sensitive than females at every studied PND. The ataxic effects were inversely proportional to the lag time from injection and to the age of animals (with P < 0.05 only between 2 and 8 week old mice). These data indicate that both the administration time and age of the animal significantly affect the neurotoxic effects of SNP.
硝普钠（SNP）作为一种强效血管扩张剂或一氧化氮供体，在药理学研究中被广泛应用。通过朱卢 - 库瓦西耶试验评估SNP对小鼠的共济失调作用。选用2至8周龄的雌雄瑞士白化小鼠，使其至少适应2周12小时光照（休息期）/12小时黑暗（活动期）的环境。在2周龄和4周龄的小鼠中，腹腔注射剂量为3至3.6 mg·kg-1的SNP后，分别在光照开始后约1小时和13小时出现最大共济失调。亚致死毒性在统计学上与给药时间相关（χ2检验：P < 0.005）。通过余弦分析未在神经毒性中验证出节律。在出生后发育第8周（PND）时，SNP诱导的共济失调在约1小时时最为严重（雄性为69%，雌性为49%），在约13小时时最低（雄性为21%，雌性为11%）（χ2检验：P < 0.00001）。余弦分析还显示，注射3或3.3 mg·kg-1的小鼠中无统计学显著节律。然而，在接受3.6 mg·kg-1处理的小鼠中，经调整的余弦分析检测到显著的昼夜节律（τ = 24小时）（P < 0.004）。在所有研究组中，SNP诱导的运动障碍（以百分比表示）在黑暗期低于光照期。此外，在每个研究的PND阶段，SNP诱导的神经元毒性存在与性别相关的非显著差异，雄性比雌性更敏感。共济失调作用与注射后的滞后时间和动物年龄成反比（仅在2周龄和8周龄小鼠之间P < 0.05）。这些数据表明，给药时间和动物年龄均显著影响SNP的神经毒性作用。
