Investigation of genotoxic effects of dexketprofen trometamol, on human cells, in vitro

Non-steroid anti-inflammatory drugs (NSAIDs) have analgesic, antipyretic and anti-inflammatory effects. Dexketoprofen belongs to NSAIDs family, which is widely used in musculoskeletal pain, dysmenorrhea, headache and toothache. In this study, we investigated poorly known genotoxic effects of dexketoprofen trometamol, used as drug substance in analgesic drugs, on healthy human lymphocytes in vitro. Cytokinesis block micronucleus (CBMN) assay, Comet assay and real-time reverse transcription polymerase chain reaction (RT-PCR) assay were employed. In the study, dexketoprofen trometamol exerted toxic effects on healthy human lymphocytes at the doses of 750 µg/mL, 1000 µg/mL and >1000 µg/mL and showed clastogenic activity at exposures to 750 µg/mL and 500 µg/mL by inducing micro-nucleus formation. In Comet parameters, drug substance also led DNA damage in the form of strand break by significantly increasing tail length and density of DNA at the dose range of 1000, 500, 250 and 100 µg/mL compared to spontaneous values. On the other hand, it was also found that expressions of XPC, XRCC6 and PNKP genes located on the plate of DNA damage signaling pathway were markedly increased in human lymphocytes treated with 750 and 100 µg/mL dexketoprofen trometamol. Based on the experimental results, it was concluded that dexketoprofen trometamol may have dose- and time-dependent cytotoxic, cytostatic and genotoxic effects on healthy human lymphocytes in vitro. We think that these findings should be supported similar or further studies.