The effects of rosmarinic acid on cisplatin toxicity in HepG2 cells

Medicinal plants are important not only as therapeutic agents, but also for pharmacological investigations and drug development. Today phytotherapy (phytos: plant, therapy: treatment) has increased interest. Phytotherapy is used for the treatment of dermatological diseases, infections and various cancer diseases. Rosmarinic acid (RA), a natural antioxidant, found in many plants such as rosemary, oregano, has antimicrobial effect. The chemotherapeutic agent, cisplatin (CisP), has a progressive effect on the development of cancer cells, but it also destroys healthy cells. Chemotherapeutic drugs are used together with phytotherapeutic compounds to increase the anticancer effect and reduce cytotoxicity. In our study, the effects of rosmarinic acid on cisplatin toxicity were examined by MTT method (3-(4,5-dimetiltriazol-2-il)-2,5-difeniltetrazolium bromid), micronucleus test and comet method on liver carcinoma cells (HepG2). The cytotoxicity of RA and CisP in HepG2 cells was determined by MTT by using different concentrations. Then, RA with CisP were used in combination to evaluate the DNA damage by micronucleus test and comet method. Different doses of RA were used, 0,125 mM, 0,25 mM, 0,5 mM, 1,25 mM, 2,5 mM, 6,25 mM, 12,5 mM, 25 mM, 50 mM on HepG2 cells along with control group for 24- hour. The LD50 value was 13,8 mM and the LD0 value was 0,01 mM. According to the MTT method results, cell viability decreased as RA concentration increased. CisP doses were 10 µg/mL, 20 µg/mL, 50 µg/mL, 100 µg/mL, 200 µg/mL, 400 µg/mL, 600 µg/mL, 800 µg/mL, 1000 µg/mL used. The LD50 value was found to be 11,06 µg/mL. After LD50 doses of RA and CisP were determined, HepG2 cells were sufficiently amplified to form 4 groups of cells. In each group, the number of n was studied at least 3. Groups; control group, RA group, CisP group and RA + CisP group. LD0 dose was used to determine the effect of RA on CisP toxicity. LD50 dose of CisP was used. 24 hours after the application to the experimental groups, the obtained cells were used in comet and micronucleus tests. The results suggest that CisP increases genotoxicity in HepG2 cells and that LD0 dose of RA may reduce genotoxicity caused by CisP toxicity. However, in order to make this clearer, it is thought that it may be useful to repeat the applications performed in this thesis study simultaneously with healthy cells.