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Well-designed randomized clinical studies are needed to systematically evaluate the evidence for the use of these hepatoprotective agents as treatment options for APAP-induced liver injury, to determine the timing of initiation of the therapy, and to further define the optimal treatment regimen

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Although Pol- has relatively low affinity for these analogues (100), their incorporation causes premature chain termination during mtDNA replication, leading to mtDNA depletion, reduced expression of -encoded OXPHOS subunits, and ultimately impaired ETC function and ATP production (101103)