Investigation of doxorubicin-induced damage on liver and the possible protective effect of propolis against this damage at molecular level

Doxorubicin (DOX), a chemotherapeutic agent widely used in the treatment of many cancers, causes serious toxic effects in non-target organs. The aim of this study is to examine the harmful effects of DOX on the rat liver and blood tissues and the possible protective effect of propolis (PRPLS), a bee product containing strong antioxidant substances, on these damage at the molecular level with Attenuated Total Reflection-Fourier Transformation Infrared (ATR-FTIR) spectroscopy and biochemical tests. For this purpose, male Sprague Dawley rats were divided into 4 groups; control (n=7), DOX (2.5 mg/kg in six injections; cumulative dose: 15 mg/kg; n=7), PRPLS (200 mg/kg, daily; n=6) and DOX + PRPLS (15 mg/kg, cumulatively; 200 mg/kg, daily; respectively; n=7). The rats were given 200 mg/kg PRPLS by oral gavage every day for 20 consecutive days and 2.5 mg/kg DOX intraperitoneally on the 10th, 12th,14th,16th, 18th and 20th day of the experiment. On the 21st day of the experiment liver and blood samples were collected, the liver tissues were examined by ATR-FTIR spectroscopy, total antioxidant level (TAS) and total oxidant level (TOS) were measured in blood plasma samples obtained from animals and oxidative stress index (OSI) was calculated. The results showed that DOX caused a decrease in the amount of glycogen and nucleic acid, an increase in the amount of lipid and protein and some important changes in the metabolism, structure and conformation of these molecules in the liver. It also induced lipid peroxidation, a decrease in membrane order and an increase in membrane dynamics. DOX also induced lipid peroxidation, an increase in membrane fluidity, a decrease in membrane alignment, and protein denaturation. The results of TAS and TOS experiments showed that DOX induces oxidative stress in the blood tissue. When PRPLS was given alone, it did not cause any toxic effects in the liver but it benefited the organism by increasing the amount of TAS in the blood. PRPLS administered before DOX, prevented the oxidative stress induced by DOX in the blood however, it was not able toshow a protective effect against the harmful effects of DOX on biomolecules in the liver. This study revealed that DOX causes significant damage to liver and blood tissues, and PRPLS at the dose and time administered here prevents oxidative stress in the blood but is insufficient to prevent this damage in liver tissue.