Oral phenytoin protects against experimental cyclophosphamide-chemotherapy induced hair loss

In the current study, effects of oral phenytoin on hair growth in cyclophosphamide-treated rats were assessed with the goal of evaluating the ability of phenytoin to suppress chemotherapy-induced hair loss. Thirty-six rats were randomly assigned to six groups (1k6) of six each (n = 6). In all groups, anagen was induced in flank skin of rats by depilation. On day 9 (anagen VI), rats were injected once with either distilled water (groups 1–3) or cyclophoshamide (groups 4–6). From day 10, rats in group 1 and 4 received oral vehicle (distilled water), groups 2 and 5 received oral phenytoin (50 mg/kg), while groups 3 and 6 also received oral phenytoin (100 mg/kg). Drug or vehicle was administered daily for a period of 28 days. The flank area was serially photographed. At the end of the experimental period, rats were sacrificed to correlate visible hair growth with a histological profile of follicle response and recovery. Glutathione (GSH), glutathione peroxidase (GPX) and lipid peroxidation status were assessed. Cyclophosphamide (CYP) treatment was associated with gross morphologic and histological evidence of hair loss in the flanks, microscopic evidence of hair-shaft thinning, increased skin lipid peroxidation, decreased GSH level, and reduction in GPX activities. Phenytoin co-administration was associated with evidence of improved hair growth, increased hair-shaft thickness, reduced skin lipid peroxidation, increased GSH level, and increased GPX activities. This study showed that oral phenytoin can suppress hair loss due to CYP therapy in rats; however, further studies are needed to evaluate its potential application in chemotherapy-induced alopecia.