TY - JOUR
TI - In vivo effect of sodium valproate on mouse liver
AU - Roma-Giannikou, E.
AU - Syriopoulou, V.
AU - Kairis, M.
AU - Pangali, A.
AU - Sarafidou, J.
AU - Constantopoulos, A.
JO - Cellular and Molecular Life Sciences (CMLS)
PY - 1999
VL - 56
TODO - 3-4
SP - 363-369
PB - 
SN - 1420-682X, 1420-9071
TODO - 10.1007/s000180050437
TODO - 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
TODO - 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.
ER -