Cytotoxicity of metronidazole (Flagyl) and misonidazole (Ro-07-0582): enhancement by lactate.
The cytotoxic activity of metronidazole (Flagyl) and misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells suspended in standard medium in sealed vials and in gassed spinner flasks has been investigated. Flagyl (5 mM) was only cytotoxic at high initial cell densities. However, when lactate (20 mM) was included in the medium the cytotoxicity of Flagyl at low cell densities was considerable, and similar to that of misonidazole under the same conditions. The relevance of this "lactate effect" to in vivo systems, and the possible mechanisms involved, are discussed.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004357:Drug Synergism; D005260:Female; D007773:Lactates / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology*; D008920:Misonidazole / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology
D007773:Lactates; D009593:Nitroimidazoles; D008795:Metronidazole; D008920:Misonidazole