Τίτλος:
In vivo effect of sodium valproate on mouse liver
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
The in vivo effect of sodium valproate (SV) on the activity of uridine diphosphate glucuronosyltransferase (UDP-GT) and hepatotoxicity in the mouse liver was studied. Mice were injected intraperitoneally (IP) with SV at doses varying from 50 to 800 mg/kg per day, for six consecutive days (dose-response group) or at a standard dose of 300 mg/g per day for 2-10 days (time-response group), whereas the controls were injected with normal saline. Valproic acid levels had a positive correlation to the dose (P < 0.001) and duration of drug administration (P = 0.006). A gradual increase in UDP-GT activity was observed in doses of up to approximately 400 mg/kg per day, whereas in higher doses the enzyme activity gradually decreased. The time course of UDP-GT activity at the standard dose of 300 mg/kg per day increased progressively, with a maximum up to the sixth day and then had a gradual reduction. Hepatic necrosis (which was unrelated to the dose or the duration of drug administration) was found in 13% of the SV-treated animals and in none of the controls. We conclude that at an optimal dose (300-400 mg/kg per day) and at a time course of 6 days, SV causes liver UDP-GT induction, whereas in higher doses and longer duration of administration, UDP-GT activity is gradually reduced. SV also causes hepatotoxicity unrelated to dose and time course.
Συγγραφείς:
Roma-Giannikou, E.
Syriopoulou, V.
Kairis, M.
Pangali, A.
Sarafidou, J.
Constantopoulos, A.
Περιοδικό:
Cellular and Molecular Life Sciences (CMLS)
Λέξεις-κλειδιά:
glucuronosyltransferase; valproic acid, animal experiment; animal tissue; article; controlled study; drug liver level; enzyme activity; intraperitoneal drug administration; liver; liver necrosis; liver toxicity; male; mouse; nonhuman, Alanine Transaminase; Animals; Anticonvulsants; Dose-Response Relationship, Drug; Female; Glucuronosyltransferase; Injections, Intraperitoneal; Liver; Male; Mice; Time Factors; Valproic Acid, Animalia
DOI:
10.1007/s000180050437
