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Although reperfusion is critical for tissue repair, it triggers more severe injury via oxidative stress, inflammatory responses, and mitochondrial dysfunction [35]: hepatocytes endure hypoxia during ischemia, and reperfusion reintroduces oxygen, triggering a burst of reactive oxygen species (ROS), intracellular calcium overload, and increased production of pro-inflammatory cytokines/chemokines, which further exacerbate hepatocyte damage, apoptosis, and necrosis [36]

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Psychological dependence is often mentioned as a reason for more frequent dosage