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The global sensitivity analysis also confirmed the importance of the redox cycle between SQ . and H 2 Q ( R 4 ), showing that the reverse rate constant, k m4 (SQ . reformation), was the second most sensitive (main interactions) with respect to model OCR and therefore ROS production, suggesting auto-oxidation is an essential part of the doxorubicin redox mechanism

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Studies with isolated hepatocytes would establish that human cells are less sensitive than those from mice, and that this difference is due to the relative rates of NAPQI formation