New and improved therapy modalities currently employed in the management of malignant diseases significantly contribute to the overall survival rate in cancer patients. Therefore, some compounds although not primarily designed as supportive drugs in chemotherapy, are promising candidates for possible clinical use. Our in vitro and in vivo experiments have demonstrated that HI-6 could “ protect” cholinesterases against the irinotecan, one of frequently used antineoplastic drugs, and in that way a part of cholinergic symptoms might be reduced. Interestingly, certain antioxidants may counteract the effects of chemotherapy-induced oxidative stress on the cell cycle and enhance the cytotoxicity of antineoplastic agents. So with the purpose to investigate the levels of oxidative stress and DNA damage (lipid peroxidation, the alkaline comet assay and micronucleus assay) related to treatments with irinotecan and HI-6 given alone or in combination we also focused on the assessment of possible antioxidative capacity of HI-6. In view of the DPPH assay results, HI-6 shows moderate radical scavenging at the tested concentration. Administration of HI-6 alone or with irinotecan diminished the levels of TBARS in rat plasma. Confirmatory results regarding HI-6 efficacy were also obtained by the alkaline comet and micronucleus assay. When given alone, it mostly did not induce significant disturbances in the level of primary DNA damage in somatic cells of treated rats and did not significantly induce the formation of micronuclei. Results obtained in the present study seems to be a proper argument to consider HI-6 as beneficial substance during chemotherapy.

Temeljne medicinske znanosti