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Time-of-day dependence of neurological deficits induced by sodium nitroprusside in young mice.

Sani M, Sebai H, Boughattas NA, Ben-Attia M - J Circadian Rhythms (2011)

Bottom Line: No rhythm was validated in neurotoxicity by cosinor analyses.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.These data indicate that both the administration time and age of the animal significantly affect the neurotoxic effects of SNP.

View Article: PubMed Central - HTML - PubMed

Affiliation: Département de Biologie, Faculté des Sciences de Maradi, Université de Maradi, 465 Maradi, Niger. sanimamane@yahoo.fr.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Variations of ataxia according to the dosing time of sodium nitroprusside in eight-week old male and female mice. The three panels refer to three doses: 3 (a), 3.3 (b) and 3.6 mg.kg-1 (c). Values are the mean ± SEM of four independent experiments. The black bar corresponds to the dark period. Maximum and minimum of motor incoordination correspond, irrespective to the gender and dose, to drug dosing at 1 and 13 HALO, respectively. A dosing time-related effect was statistically validated by χ2 test (P < 0.00005) in both genders. Circadian (τ = 24 h) rhythms were confirmed by Cosinor analysis with correction for multiple testing only in mice treated with 3.6 mg.kg-1 (P < 0.05).
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Figure 3: Variations of ataxia according to the dosing time of sodium nitroprusside in eight-week old male and female mice. The three panels refer to three doses: 3 (a), 3.3 (b) and 3.6 mg.kg-1 (c). Values are the mean ± SEM of four independent experiments. The black bar corresponds to the dark period. Maximum and minimum of motor incoordination correspond, irrespective to the gender and dose, to drug dosing at 1 and 13 HALO, respectively. A dosing time-related effect was statistically validated by χ2 test (P < 0.00005) in both genders. Circadian (τ = 24 h) rhythms were confirmed by Cosinor analysis with correction for multiple testing only in mice treated with 3.6 mg.kg-1 (P < 0.05).

Mentions: In 2 week old mice, sodium nitroprusside-induced locomotor impairment (ataxia) was least at 9 HALO, affecting only 30% of the animals, and was greatest at 1 and 13 HALO, affecting 62% and 56% of the animals (χ2 = 16.51, P < 0.005), respectively (Figure 1). Similarly, in the young-weaned (4 week old) mice, drug dosing at 1 and 13 HALO resulted in highest ataxia (Figure 2). Ataxia rate differed as a function of SNP dosing-time, the difference being validated by χ2 test (P < 0.005). In both genders, no statistically significant rhythm was detected by Cosinor analyses (Tables 1 and 2). With the three used doses (3.0, 3.3, and 3.6 mg.kg-1), the ataxic effects were higher in males than in females but not statistically significant. The gender-related difference in ataxia rates persisted until age 8 weeks, but their respective value was 19% and 35% lower than the rate at age 2 weeks. Moreover, with the exception of the 4 week old male mice (P ≤ 0.01: χ2 test between doses 3.0 and 3.6 mg.kg-1), there was no statistically significant dose-dependent ataxia at any postnatal development (PND) stage. Chronograms of ataxia at age 8 week (Figure 3) show curve patterns with the peak time located at ≈ 1 HALO (69% in males vs. 49% in females) and the trough time at ≈ 13 HALO (21% in males vs. 11% in females) (P < 0.00001: χ2 test). No statically significant rhythm was detected in 3 and 3.3 mg.kg-1-treated 8 week old mice. However, a significant 24 h rhythm was detected by Cosinor analysis in mice treated with 3.6 mg.kg-1 (P < 0.004). The behavioural neurotoxicity was inversely proportional to the age of animals; with significant (P < 0.05) difference only between 2 and 8 week old mice.


Time-of-day dependence of neurological deficits induced by sodium nitroprusside in young mice.

Sani M, Sebai H, Boughattas NA, Ben-Attia M - J Circadian Rhythms (2011)

Variations of ataxia according to the dosing time of sodium nitroprusside in eight-week old male and female mice. The three panels refer to three doses: 3 (a), 3.3 (b) and 3.6 mg.kg-1 (c). Values are the mean ± SEM of four independent experiments. The black bar corresponds to the dark period. Maximum and minimum of motor incoordination correspond, irrespective to the gender and dose, to drug dosing at 1 and 13 HALO, respectively. A dosing time-related effect was statistically validated by χ2 test (P < 0.00005) in both genders. Circadian (τ = 24 h) rhythms were confirmed by Cosinor analysis with correction for multiple testing only in mice treated with 3.6 mg.kg-1 (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3141784&req=5

Figure 3: Variations of ataxia according to the dosing time of sodium nitroprusside in eight-week old male and female mice. The three panels refer to three doses: 3 (a), 3.3 (b) and 3.6 mg.kg-1 (c). Values are the mean ± SEM of four independent experiments. The black bar corresponds to the dark period. Maximum and minimum of motor incoordination correspond, irrespective to the gender and dose, to drug dosing at 1 and 13 HALO, respectively. A dosing time-related effect was statistically validated by χ2 test (P < 0.00005) in both genders. Circadian (τ = 24 h) rhythms were confirmed by Cosinor analysis with correction for multiple testing only in mice treated with 3.6 mg.kg-1 (P < 0.05).
Mentions: In 2 week old mice, sodium nitroprusside-induced locomotor impairment (ataxia) was least at 9 HALO, affecting only 30% of the animals, and was greatest at 1 and 13 HALO, affecting 62% and 56% of the animals (χ2 = 16.51, P < 0.005), respectively (Figure 1). Similarly, in the young-weaned (4 week old) mice, drug dosing at 1 and 13 HALO resulted in highest ataxia (Figure 2). Ataxia rate differed as a function of SNP dosing-time, the difference being validated by χ2 test (P < 0.005). In both genders, no statistically significant rhythm was detected by Cosinor analyses (Tables 1 and 2). With the three used doses (3.0, 3.3, and 3.6 mg.kg-1), the ataxic effects were higher in males than in females but not statistically significant. The gender-related difference in ataxia rates persisted until age 8 weeks, but their respective value was 19% and 35% lower than the rate at age 2 weeks. Moreover, with the exception of the 4 week old male mice (P ≤ 0.01: χ2 test between doses 3.0 and 3.6 mg.kg-1), there was no statistically significant dose-dependent ataxia at any postnatal development (PND) stage. Chronograms of ataxia at age 8 week (Figure 3) show curve patterns with the peak time located at ≈ 1 HALO (69% in males vs. 49% in females) and the trough time at ≈ 13 HALO (21% in males vs. 11% in females) (P < 0.00001: χ2 test). No statically significant rhythm was detected in 3 and 3.3 mg.kg-1-treated 8 week old mice. However, a significant 24 h rhythm was detected by Cosinor analysis in mice treated with 3.6 mg.kg-1 (P < 0.004). The behavioural neurotoxicity was inversely proportional to the age of animals; with significant (P < 0.05) difference only between 2 and 8 week old mice.

Bottom Line: No rhythm was validated in neurotoxicity by cosinor analyses.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.These data indicate that both the administration time and age of the animal significantly affect the neurotoxic effects of SNP.

View Article: PubMed Central - HTML - PubMed

Affiliation: Département de Biologie, Faculté des Sciences de Maradi, Université de Maradi, 465 Maradi, Niger. sanimamane@yahoo.fr.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus