Protection of Chinese hamster ovary cells from paraquat-mediated cytotoxicity by a low molecular weight mimic of superoxide dismutase (DF-Mn).
Paraquat exerts a cytotoxic effect on Chinese hamster ovary cells in culture via the superoxide radical (O2-). We have described a superoxide dismutase (SOD) mimic based on manganese (DF-Mn) which consists of a one-to-one complex between desferrioxamine B (Desferal) and MnO2. It is a small molecular weight molecule, easy to prepare and possesses considerable stability. It is now shown to protect mammalian cells from paraquat toxicity. Thus, 20 microM DF-Mn affords up to complete protection against the cytotoxicity of 200 microM paraquat in Chinese hamster ovary cells. Desferrioxamine B or MnO2 alone gave no protection. MnCl2 or catalase provided little or no protection against the paraquat, respectively. Equivalent amounts of human Cu-Zn SOD in terms of activity, also provided no protection. Copper diisopropylsalicylate (CuDIPS) provided limited, yet significant, protection, but this is explained in terms other than SOD activity. Finally, at higher concentrations, purified human SOD, exerts a limited toxicity as well as a protective ability against paraquat (similar to DF-Mn) both of which are eliminated upon heat denaturation of the enzyme. It appears that the SOD mimic, DF-Mn, can enter mammalian cells and can protect against the cytotoxic effects of O2-.
Darr
D J
DJ
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Yanni
S
S
Pinnell
S R
SR
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005260:Female; D008345:Manganese / Q000494:pharmacology*; D017895:Manganese Compounds; D008970:Molecular Weight; D010053:Ovary / Q000166:cytology*; D010087:Oxides; D010269:Paraquat / Q000633:toxicity*; D012459:Salicylates / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology
D004338:Drug Combinations; D017895:Manganese Compounds; D010087:Oxides; D012459:Salicylates; C030865:copper bis(3,5-diisopropylsalicylate); D008345:Manganese; C027424:manganese oxide; D013482:Superoxide Dismutase; D003676:Deferoxamine; D010269:Paraquat