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The four-pathway approach activates mechanisms that single or dual agonists cannot reach, potentially overcoming resistance that develops with prolonged use of less comprehensive compounds

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Consistent with perturbed glutathione metabolism, CLP mice exhibited significant downregulation of the Nrf2/HO-1 antioxidant axis: reduced Nrf2, a master transcriptional regulator of antioxidant genes, and its target HO-1 were reduced, indicating impaired upstream antioxidant regulation

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