title: Preliminary studies evaluating cytotoxic effect of combined treatment with methotrexate and simvastatin on green monkey kidney cells.
abstract: Patients, affected by neoplastic disease, take usually other drugs and this may lead to a number of often rather unpredictable interactions. The statins are among the most commonly prescribed drugs in medicine but have also adverse side effects and come into interactions with other drugs. The aim of this study was to investigate the cytotoxic effect of methotrexate (5.5 or 16.5 micromol/L), simvastatin (100 or 300 micromol/L) and their combination on green monkey kidney (GMK) cells culture using cytotoxicity detection kit LDH. Besides, the effect of above drugs on the cells viability was estimated by MTT test. After 6, 12 or 24 h of simultaneous incubation of GMK cells with methotrexate (5.5 micromol/L) and simvastatin (100 micromol/L) the cytotoxicity (about 10%) of the drugs was found in LDH test. Cytotoxicity of combination: methotrexate (5.5 micromol/L) with simvastatin (300 micromol/L) after 6 or 12 h of incubation with GMK cells was similar (about 10%), but after 24 h of incubation, cytotoxicity increased to 21%. The significant increase of the cytotoxicity (about 30%) was found after 24 h incubation of GMK cells with methotrexate (16.5 micromol/L) and simvastatin (100 micromol/L). In the MTT assay, the decrease in the cells viability was found also after 12 and 24 h of GMK cells incubation with methotrexate (5.5 or 16.5 micromol/L) and simvastatin (100 or 300 micromol/L). These results suggest the adverse effect of combined application of both drugs on GMK cells especially after 24 h of incubation.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Izdebska
authors.forename: Dorota
authors.initials: D
authors.lastname: Natorska-Chomicka
authors.forename: Ewa
authors.initials: E
authors.lastname: Jagiełło-Wójtowicz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008727:Methotrexate / Q000633:toxicity*; D019338:Polypharmacy; D019821:Simvastatin / Q000633:toxicity*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D007770:L-Lactate Dehydrogenase; D008727:Methotrexate