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Unlabelled: The purpose of this study was to investigate if the oxidative effects of sodium nitroprusside (SNP) are dosing-time dependent. Therefore, the variation of malondialdehyde (MDA) status was assessed after a single i.p. administration of SNP (2.5mgkg(-1) b.w.) or vehicle (9‰ NaCl) to different and comparable groups of mice (n=48) at two different circadian times (1 and 13h after light onset [HALO]). Brain, kidney, and liver tissues were excised over 36h, and their MDA contents were estimated at 0, 1, 3, 6, 9, 12, 24, and 36h after SNP administration., Results: indicated mean MDA level was not significantly changed in each investigated tissue compared with the control. In contrast, the mean MDA value varied among organs and was comparable in brain and liver but lower than in kidney. The data show SNP significantly (P<0.05) increases MDA status in both tissues and exerts time-dependent oxidative effects with the greatest toxicity coinciding with the beginning of the diurnal rest span (local time: 08:00h, i.e., at 1 HALO). The obtained results reveal SNP-induced oxidative damage (evidenced by MDA accumulation) varies according to both the dosing-time and the target organ., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Primary Objective: To study the protective effect of resveratrol on endotoxemia-induced neurotoxicity., Methods: Rats were pre-treated during 7 days with 20 mg kg(-1) body weight (b.w.) resveratrol and challenged with a single dose of lipopolysaccharide (LPS: 8 mg kg(-1) b.w.) for 24 hours. Brains were harvested to determine LPS-induced lipoperoxidation level, antioxidant enzyme activities, nitric monoxide (NO) and iron distribution as well as the impact of resveratrol on these parameters., Results: Resveratrol counteracted LPS-induced brain malondialdehyde (MDA) level and antioxidant enzyme activities depletion as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). Resveratrol also reversed LPS-induced brain and plasma NO elevation as well as iron sequestration from plasma to brain compartment., Conclusion: The data suggest that resveratrol is capable of alleviating LPS-induced neurotoxicity by a mechanism that may involve iron shuttling proteins.

Rhodanese (thiosulfate sulfurtransferase) is a ubiquitous enzyme that accelerates the transformation of cyanide into the very less toxic thiocyante. Influence of cerebral rhodanese level on cyanide toxicity has already been shown in mice. However, age-related changes in rhodanese activity have not been previously examined. The aim of the experiments was to investigate age-related changes of cerebral rhodanese activity in male and female mice maintained from birth to age 16 weeks under 12:12 light:dark (LD) cycle conditions. The rhythm of enzyme activity was quantified by Cosinor test programme in 2-, 4-, 8-, 12-, and 16-week-old mice. Significant ultradian (tau =1 2h) rhythms were validated both by ANOVA (P < 0.05) and Cosinor analyses (P < or = 0.01) in 2- and 4-week-old mice. However, in addition to the ultradian rhythm, a significant (P < or = 0.01) prominent circadian (tau = 24h) rhythm, whose peak time located at approximately 9 Hours After Light Onset (HALO), was detected in 4-week-old females. In 8-, 12-, and 16-week-old mice, the Cosinor validated significant (P < or = 0.0001) circadian rhythms in both genders. The circadian peak time initially located at approximately 5 HALO in 8-week-old mice, moved to approximately 9 HALO and then to be stabilized at approximately 17 HALO in 12- and 16-week-old mice, respectively. Furthermore, the ultradian components were detected in 8- and 12-week-old females. On the other hand, at age 16 weeks, no significant ultradian rhythm was detected in males or in females. The enzyme activity was greater in females compared to males during the first 8 postnatal weeks. Two-way ANOVA revealed a significant (P < 0.02) interaction between circadian time and gender in 4-, 8-, 12-, and 16-week-old mice, suggesting the influence of gender on time-related changes in rhodanese activity. However, though ANOVA validated significant changes related to both sampling-time and gender, no interaction was detected between the two factors in 2-week-old mice, illustrating the gender-related difference in enzyme activity was greater. Moreover, the obtained results showed that rhodanese activity significantly increased with age during the postnatal development (PND). However, this increase would be limited by age in old mice as early as 12 weeks after birth. The data also showed a 12h phase-shift of the circadian rhodanese peak time during PND, suggesting that the rhythm stabilization is age dependent. The main findings of this study indicated that the increased sensitivity to cyanide, generally reported in old mice, may be due in part to a decrease in the activity of brain rhodanese.

Loratadine is a second-generation histamine H(1)-receptor antagonist used in the treatment of allergic diseases. The aim of the study was to assess whether lethal toxicity and motor incoordination (neurotoxicity) of loratadine is circadian rhythm-dependent. A total of 210 male Swiss mice, aged 10 wk, were synchronized for 3 wk to 12 h light (rest span)/12 h dark (activity span). The drug was administered per os. The choice of the sublethal (TD(50) = 82 mg/kg body weight) and the lethal (LD(50) = 4 g/kg body weight) dosage was based on preliminary studies. Each of these two doses was administered to comparable groups of animals at six different circadian time points (1, 5, 9, 13, 17, and 21 Hours After Light Onset [HALO]). The survival duration was dosing time-dependent (chi(2) = 16.96; p < 0.001). Drug dosing at 17 HALO resulted in best (67%) survival rate; whereas, dosing at 9 HALO resulted in poorest (21%) survival rate. Cosinor analyses (with a trial period tau = 24 h) validated a statistically significant circadian rhythm in survival rate (p < 0.04) with an acrophase (peak time Ø of best tolerance to loratadine) being at 17.5 HALO +/- 4.65 h. Troughs of motor incoordination were located at the administration times of 5 and 17 HALO (60% and 32% of animals affected, respectively), whereas peaks were located at 9 and 21 HALO (87% and 68% of animals affected, respectively). The 24 h mean of the motor incoordination was 61%, the mean proportion of animals affected by the treatment for the six different circadian times studies. The extent of this neurotoxic effect varied as a function of loratadine dosing time (p < 0.001). A statistically significant ultradian component rhythm (p < 0.01) with a trial period tau = 12 h was also validated. The obtained results show that the dosing time of loratadine at the mid-activity (dark) span seems to be optimal, since it corresponds to the longest (21 vs. 12 days) survival span and to least neurotoxicity.