Daniel Conei; Gustavo Saint-Pierre & Rodrigo Muñoz-Cofré

Side effects of antiepileptic drugs (AEDs) are the main limiting factors in adherence to treatment, highlighting cosmetic effects, such as alopecia. One of the most used is valproic acid (VPA), which causes hair loss and alopecia, being more frequent at higher doses, chronic treatments and/or in women. VPA causes an increase in reactive oxygen species, which causes alopecia and reduced expression of proteins such as Sonic Hedgehog (Shh), which can be counteracted with vitamin E (VE). The research aimed to determine the immunoexpression of Shh in the epidermis and hair follicles of mouse fetuses exposed to VPA, VPA+VE and VE. Four groups of pregnant female BALB/c mice (Mus musculus) were formed, to which the control group was administered 0.3 mL physiological serum, the VPA group 600 mg/kg, the VPA group 600 mg/kg + VE 200 IU/kg and the VE group 200 IU/kg, orally, chronic dose. At 17.5 days post-coital, the fetuses were extracted and immunohistochemistry was performed with polyclonal Shh antibody, 1:100 dilution from serial histological sections at the thoracic level. The morphology of the positively labeled samples was described, the integrated optical density (IOD) and percentage of immunoreactive area (%) in the dermis and developing hair follicles were measured. Shh immunostaining was positive in epidermis and developing hair follicles. At IOD, the VPA group showed a lower intensity of immunoreaction compared to the control, VPA+VE and VE groups (p<0.0001). Regarding the percentage of immunopositive area, the VPA group showed a lower percentage of immunoreaction compared to the control group (p<0.0001), VPA+VE group (p<0.001) and VE group (p<0.005). There were no significant differences between the control, VPA+VE and VE groups. Vitamin E modulates VPA-induced alterations in the expression of Shh in the epidermis and hair follicles in fetuses.

KEYWORDS: Skin; Hair follicles; Valproic acid; Vitamin E.

CONEI, D.; SAINT-PIERRE, G. & MUÑOZ-COFRÉ, R. Immunohistochemical effect of vitamin E and valproic acid on the development of epidermis and hair follicles. Int. J. Morphol., 43(1):203-208, 2025.