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Knocking out Nrf2 or using HO-1 antagonist reversed DOX-induced heart injury and death in mice, indicating that free iron released by heme degradation is a prerequisite for inducing heart injury

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Moreover, a minor proportion of this agent can be metabolized within the liver by the cytochrome P450 enzymes (primarily by CYP2E1) to NAPQI, which is detoxified by conjugation and excreted in the glutathione or NAC forms ( Figure 2 )