Objective: The main reason of the Doxorubicin (DOX) toxicity, which is widely used among chemotherapeutics, on many organs is the increased reactive oxygen species (ROS) and oxidative stress. Therefore, our study aimed to evaluate the possible roles of Dynamin 1 Like (DRP1) and Mitofusin 2 (MFN2), which are associated with mitochondria and oxidative stress, in the therapeutic effects of hesperetin (HST), a powerful antioxidant, on DOX-induced hepatotoxicity.

Materials and Methods: 28 Sprague-Dawley male rats were divided into 4 groups: Control, DOX, DOX+HST, and HST (n=7). DOX was administered intraperitoneally as a single dose of 15 mg/kg. HST was performed by oral gavage at a dose of 50 mg/kg every other day for 28 days. Total antioxidant level (TAS) and total oxidant level (TOS) were determined in serum samples of decapitated rats. Hematoxylin-eosin staining was performed for histopathological evaluations in liver tissues. The avidin-biotin-peroxidase method was used for DRP1 and MFN2 immunoreactivities. The qPCR was used to determine the DRP1 and MFN2 mRNA levels.

Results: Compared to the control group, it was determined that TAS level decreased, TOS level increased, histopathological findings increased, DRP1 expression level increased and MFN2 expression level decreased in the DOX group (P<0.05). Besides, in the DOX+HST group, it was found that TAS level increased, TOS level decresed, histopathological findings decreased, DRP1 expression level decreased and MFN2 expression level increased compared to the DOX group (P<0.05).

Conclusion: These results suggest that DRP1 and MFN2 may play a role in the therapeutic effects of HST on DOX-induced hepatotoxicity.