title: The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid.
abstract: Valproic acid (VPA) is a widely used and well-tolerable antiepileptic drug in epileptic patients. However, VPA has many side effects dose-dependent or non-dose-dependent. It is reported that VPA treatment may lead to biotin deficiency and low serum and liver tissue biotinidase enzyme activity (BEA). Major clinical manifestations in biotin deficiency are seborrheic dermatitis, dry skin, fine and brittle hair, and alopecia. We aimed to investigate the effects of biotin supplementation on serum and liver tissue BEA and alopecia during VPA therapy. Rats were randomly divided into 4 groups, each consisted of 15 rats (VPA-B1, VPA-B2, VPA, and control). Except the control group, all groups were administrated VPA dose of 600 mg/kg/d per oral (PO) for 60 days with 12h intervals two divided doses. VPA-B1 was administrated biotin dose of 6 mg/kg/d and VPA-B2 was administrated biotin dose of 0.6 mg/kg/d. In the third week of the study, we determined alopecia in the study groups. Alopecia was seen in the subjects of 13.3% of VPA-B1 (n=2), 13.3% of VPA-B2 (n=2), and 40% of VPA (n=6). But statistical significant effect on alopecia by biotin supplementation was not able to be determined between the study groups. In the control group, alopecia was not observed. The ratios of alopecia in the study groups were statistically higher than the control group (p=0.028). Itchiness was more obvious in the study groups compared with the control group. Serum biotin levels of the biotin supplemented groups (VPA-B1 and VPA-B2) were higher than the other groups (VPA and control group). Serum biotin levels of the VPA group were lower than the control group. There were significant decreases in the levels of serum and liver tissue BEA of the study groups compared with the control group. In conclusion we showed that VPA usage reduced the serum and liver tissue BEA and impaired the biotin utilization by affecting the liver. Partial biotinidase deficiency may lead to alopecia. It might be prevented by biotin supplementation in the patients receiving VPA therapy. We considered that further studies are necessary to find out the effective and safe biotin dose.
authors.affiliation: Department of Pediatrics, Gulhane Military Medical Academy, School of Medicine, Turkey.
authors.forename: Mutluay
authors.initials: M
authors.lastname: Arslan
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Vurucu
authors.forename: Necati
authors.initials: N
authors.lastname: Balamtekin
authors.forename: Bulent
authors.initials: B
authors.lastname: Unay
authors.forename: Ridvan
authors.initials: R
authors.lastname: Akin
authors.forename: Ismail
authors.initials: I
authors.lastname: Kurt
authors.forename: Okan
authors.initials: O
authors.lastname: Ozcan
mesh_terms: D000505:Alopecia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D001361:Avitaminosis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D001710:Biotin / Q000172:deficiency* / Q000494:pharmacology* / Q000627:therapeutic use; D043523:Biotinidase / Q000097:blood / Q000187:drug effects; D028921:Biotinidase Deficiency / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D001710:Biotin; D043523:Biotinidase