Investigation of the protective effect of curcumin in rats with doxorubicin induced experimental hepatotoxicity at light and electron microscopic levels

Purpose Objective: Determining the possible ameliorative effects of curcumin on liver damage caused by doxorubicin will contribute to the reduction of drug-induced hepatotoxicity used during cancer treatment and the success of cancer treatment. Materials and Methods: In the present study, 28 Wistar type albino rats were divided into 4 groups and an experimental model was created. Group 1: Control group (n=7): 1 ml of olive oil was given by gavage every day for 6 weeks. Group 2: Curcumin control group (n=7): Curcumin was given by gavage at a dose of 200 mg/kg/day dissolved in 1 ml olive oil for 6 weeks. Group 3: Doxorubicin group (n=7): 1mg/kg twice a week for 6 weeks, a total of 2mg/kg/week Doxorubicin was administered via ip. Group 4: Doxorubicin+Curcumin group (n= 7): 2 hours after curcumin was given by gavage 200 mg/kg/day, Doxorubicin was administered as 2 mg/kg/week ip. At the end of the sixth week, intracardiac blood was collected from rats under anesthesia for biochemical analysis, and liver tissues taken for light and electron microscopic examination were prepared in accordance to tissue preparation techniques. Results: While the doxorubicin administered group was characterized by significant weight loss, increased liver enzymes ALT and AST levels, decreased SOD activity, and increased MDA activity, in the doxorubicin and curcumin administered group, all these values were similar to the values in the control groups. Additionally, TNF-α and Caspase-3 immunohistochemical expressions were significantly increased in the doxorubicin group while these expressions were significantly decreased in the doxorubicin+curcumin group. In the group administered with Doxorubicin histochemical staining revealed an increase in collagen fibers in the liver, light and electron microscopic evaluations showed pycnotic nuclei in hepatocytes, degeneration and aggregation in mitochondria, degenerative changes characterized by aggregation in GER cisterns, as well as inflammatory cell infiltration, congestion and increase in ito cells and eosinophils were observed. Biochemical, immunohistochemical, histochemical, light and ultrastructural evaluations in the doxorubicin+curcumin group were similar to those in the control group. Conclusion: In the doxorubicin administered rats, weight loss and changes in the liver enzyme levels were detected, along with increased occurrence of programmed cell death called as apoptosis and necroptosis, and formation of fibrosis were observed while it was observed that apoptosis and necroptosis events were decreased in the doxorubicin and curcumin administered group, and no fibrosis event was observed. Therefore it is concluded that the use of curcumin has protective and curative effects on hepatocytes with doxorubicin induced hepatotoxicity.