| 15062877 |
Komarov AM, Hall JM, Weglicki WB: Azidothymidine promotes free radical generation by activated macrophages and hydrogen peroxide-iron-mediated oxidation in a cell-free system. FEBS Lett. 2002 Jul 17;523(1-3):128-32.
Azidothymidine (AZT) and AZT monophosphate (AZT-MP) in concentrations as low as 10 and 50 microM, respectively, promote oxidation of chemically deacetylated 2',7'-dichlorodihydrofluorescein (DCDHF) to 2',7'-dichlorofluorescein (DCF) by rat peritoneal macrophages activated with latex. Cells were incubated with AZT and AZT-MP for 18 h, washed out from residual AZT or AZT-MP and activated with latex for 30 or 60 min in the presence of DCDHF. Latex-activated cells oxidize DCDHF extracellularly due to release of hydrogen peroxide and low-molecular iron complexes, which is verified using catalase, desferal and the peroxidase inhibitor sodium azide. AZT and AZT-MP increase DCDHF oxidation due to additional release of hydrogen peroxide as demonstrated by catalase inhibition of DCDHF oxidation and direct H (2) O (2) measurement. Thymidine and thymidine phosphates did not show any effect on macrophage activation. In separate experiments we evaluated the in vitro prooxidant activity of AZT, AZT-MP, AZT triphosphate (AZT-TP), AZT glucuronide (GAZT) and 3'-amino-3'-deoxythymidine (AMT) in a cell-free system using the hydrogen peroxide-iron-mediated oxidation of DCDHF. Under these conditions, AZT and AZT phosphates exhibit a prooxidant effect in concentrations as low as 100 microM. Furthermore, GAZT is a less effective prooxidant and AMT acts like an antioxidant. Thymidine did not show any effect. |
82(1,1,1,2) |