Abstract
Background. Chemotherapy with alkylating agents such as melphalan can induce neurotoxic effects in the hippocampus. This study was conducted to investigate the protective effect of chrysin on melphalan-induced histopathological changes and the expression of autophagy-related genes in the rat hippocampus.
Methods. In this experimental study, 48 male Wistar rats (21 days old) were randomly assigned to six groups: a control group, a melphalan-treated group (0.5 mg/kg, intraperitoneally), two groups receiving melphalan in combination with chrysin (25 and 50 mg/kg, respectively, orally), and two groups receiving chrysin alone (25 and 50 mg/kg, respectively, orally). The treatment period for the groups receiving melphalan and/or chrysin was 14 days. At the end of the experimental period, hippocampal histological changes were assessed using toluidine blue staining, and the expression of autophagy-related genes was evaluated using real-time PCR.
Results. The administration of melphalan significantly increased the number of dark neurons and significantly decreased the expression of autophagy-related genes compared with the control group. Treatment with chrysin (50 mg/kg) significantly reduced the number of dark neurons and increased the expression of autophagy-related genes.
Conclusion. The administration of chrysin was associated with reduced melphalan-induced histopathological alterations and modulation of the expression of autophagy-related genes in the hippocampus. These findings suggest that changes in the expression of autophagy-related genes may play an important role in the protective response of chrysin against melphalan-induced neuronal injury.
Practical Implications. Chrysin was associated with favorable changes in histopathological indices and the expression of autophagy-related genes in this animal model. However, further pharmacokinetic studies, evaluation of brain tissue penetration, safety assessment, and investigation of its potential effects on the antitumor efficacy of melphalan are required before clinical translation.