Redox properties and prooxidant cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX)

• Autorzy: Sarlauskas J. , Nemeikaite-Ceniene A. , Miseviciene L. , Krikstopaitis K. , Anusevicius Z. , Cenas N.
• Języki publikacji: EN

Abstrakty

EN

 In order to characterize the possible mechanism(s) of cytotoxicity of a neuroleptic agent 6,7-dinitrodihydroquinoxaline-2,3-dione (DNQX) we examined the redox properties of DNQX, and its mononitro- (NQX) and denitro- (QX) derivatives. The irreversible electrochemical reduction of the nitro groups of DNQX was characterized by the reduction peak potentials (Ep,7) of -0.43 V and -0.72 V vs. Ag/AgCl at pH 7.0, whereas NQX was reduced at Ep,7 = -0.67 V. The reactivities of DNQX and NQX towards the single-electron transferring enzymes NADPH:cytochrome P-450 reductase and NADPH:adrenodoxin reductase/adrenodoxin complex were similar to those of model nitrobenzenes with the single-electron reduction potential (E17) values of -0.29 V - -0.42 V. DNQX and NQX also acted as substrates for two-electron transferring mammalian NAD(P)H:quinone oxidoreductase (DT-diaphorase). The cytotoxicity of DNQX in bovine leukemia virus-transformed lamb kidney fibroblasts (line FLK) was prevented by antioxidants and an inhibitor of NQO1, dicoumarol, and was enhanced by the prooxidant alkylating agent 1,3-bis(2-chloromethyl)-1-nitrosourea. A comparison with model nitrobenzene compounds shows that the cytotoxicity of DNQX and NQX reasonably agrees with the ease of their electrochemical reduction, and/or their reactivities towards the used enzymatic single-electron reducing systems. Thus, our data imply that the cytotoxicity of DNQX in FLK cells is exerted mainly through oxidative stress.

Słowa kluczowe

EN

redox property; prooxidant; cytotoxicity; neuroleptic drug 6,7-dinitrodihydroquinoxaline-2,3-dione; flavoenzyme; oxidative stress

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2013
• Tom: 60
• Numer: 2
• Opis fizyczny: p.227-231,fig.,ref.

Twórcy

autor

Sarlauskas J.

• Institute of Biochemistry, Vilnius University, Vilnius, Lithuania

autor

Nemeikaite-Ceniene A.

• Center of Innovative Medicine, Vilnius, Lithuania

autor

Miseviciene L.

• Institute of Biochemistry, Vilnius University, Vilnius, Lithuania

autor

Krikstopaitis K.

• Institute of Biochemistry, Vilnius University, Vilnius, Lithuania

autor

Anusevicius Z.

• Institute of Biochemistry, Vilnius University, Vilnius, Lithuania

autor

Cenas N.

• Institute of Biochemistry, Vilnius University, Vilnius, Lithuania

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