Valproic acid (VPA) is an
antiepileptic drug widely used and well-tolerated by most of patients. Its non-dose-dependent side effects seen mostly are the temporary gastrointestinal disturbances including
anorexia and
nausea, and hepatoxicity. As to its dose-dependent side effects are the
weight loss,
tremor, skin eruption and the
alopecia. In this study we aimed to put forward the
biotinidase deficiency considered as a possible cause of
alopecia in the rats administered with
valproic acid, and the correlation between liver and serum
biotinidase enzyme activities (BEA) and
transaminases,
albumin and serum
valproic acid levels. In our study, 4 groups of which one of them was a control group, each consisting of 15 male Wistar rats was organized. 200, 400, and 600 mg/kg/day of VPA, and distilled water, two divided doses per day, were administered per orally to VPA-1, VPA-2, VPA-3, and control group, respectively, in 60 days. Their serum and liver
biotinidase enzyme activities, serum AST, ALT,
albumin, and
valproic acid levels were measured.
Alopecia was seen in the subjects of 6.6% of VPA-1, 13.3% of VPA-2, and 26.6% of VPA-3. Significant difference in the liver tissues BEA was noted only between VPA-3 and the control group. Reductions were observed both in the liver tissues BEA and the serum BEA levels, which are inversely proportional to the VPA doses. A positive correlation between the liver
biotinidase enzyme activities and the serum
valproic acid levels, and the negative correlation between the liver tissues
biotinidase activities and the serum
valproic acid levels were noted, respectively. As a conclusion, the partial
alopecia which is an initial symptom of reduced
biotinidase activity may also be created depending on the reduction of
biotinidase activity during
valproic acid therapy. The
alopecia which may further be observed in the patients receiving
valproic acid therapy may be prevented by means of administration of
biotin in a dose of 10 mg/day.