Circadian time-dependent hepatic and renal toxicities to valproic acid in mice |
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| Authors: | Wafa Ben-Cherif Ichrak Dridi Zohra Haouas Abdelhedi Miled Karim Aouam Mossadok Ben-Attia |
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| Institution: | 1. Laboratory of Pharmacology, Faculty of Medicine, University of Monastir, 5000 Monastir, Tunisia;2. Laboratory of Histology-Cytology and Genetics (02/UR/08-03), Faculty of Medicine, University of Monastir, 5019 Monastir, Tunisia;3. Department of Biochemistry CHU Hached, Sousse 4002, Tunisia;4. Laboratory of Biomonitoring of the Environment (LR01/ES14), Faculty of Sciences of Bizerte, University of Carthage, 7021 Zarzouna, Bizerte, Tunisia |
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| Abstract: | This study aims to investigate whether hepatic and renal valproic acid (VPA) toxicities varied according to the dosing time in the 24-h scale in mice. VPA was administered by i.p. route to different groups of animals at four different circadian stages (1, 7, 13, and 19 h after light onset (HALO)). Biochemical study and histopathological examinations on liver and kidney sections were performed. The results showed that the hepatic and renal toxicity induced by VPA was time related. Animals treated at 19 HALO showed vacuolar degenerative changes, congestions, and inflammatory areas on liver parenchyma. Lesions within proximal tubules were observed in the kidney in groups treated at 19 HALO. The largest increases in alanine aminotransferase, alkaline phosphatase and plasma creatinine activities were also observed at 19 HALO. The obtained data indicate that the optimal hepatic and renal tolerance is observed when VPA was injected in the middle of the light-rest span of mice. |
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| Keywords: | valproic acid Cosinor method hepatic toxicity renal toxicity mice circadian rhythm |
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