In vitro and in vivo assessment of indomethacin-induced genotoxicity: protection by curcumin.

Abstract

Indomethacin is one of the most widely used non-steroidal anti-inflammatory drugs. This study aimed to investigate the protective effects of curcumin against indomethacin-induced genotoxicity. For in vitro studies, human peripheral blood lymphocytes were obtained from a healthy volunteer and treated for 24 h as follows: vehicle control, indomethacin at 100 and 200 μΜ, indomethacin (100 μM and 200 μM) plus curcumin (27 μM). For in vivo experiments, mice received a single i.p dose of curcumin (100 mg/kg) and after 30 min genotoxicity induction was carried out by a single i.p injection of indomethacin at 10, 20, and 40 mg/kg. After 24 h, bone marrow cells were obtained from mice femurs. Genotoxicity was evaluated using a micronucleus assay. Oxidative damage was also inspected both in vitro and in vivo. In-vitro studies indicated that co-treatment with curcumin caused a significant decrease in the average micronuclei percentage and MDA level, and a significant increase in GSH concentration compared to the groups treated only with indomethacin. In-vivo findings revealed that pretreatment with curcumin induced a significant increase in the average ratio of polychromatic erythrocyte/normochromic erythrocyte, GSH concentration and caused a significant decrease in the average percentage of micronuclei and MDA level, in comparison with the group treated only with indomethacin. Curcumin attenuated indomethacin-induced genotoxicity both in vitro and in vivo. These effects might be partially exerted by decreasing oxidative stress. Further studies are required to elucidate the exact genoprotective mechanism of curcumin against indomethacin.