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p38 MAPK pathway inhibition with SB203580 and macrophage depletion further alleviated the above effects in DOX-treated IL-22-knockout mice. The effects were stronger IL-22-knockout mice with adoptive transfer of WT macrophages than in those with adoptive transfer of IL-22-knockout macrophages. Furthermore, increasing the expression of Fizz3 reduced cardiomyocyte apoptosis and alleviated cardiac dysfunction. Our results may suggest that IL-22 knockout alleviate DOX-induced oxidative stress and cardiac injury by inhibiting macrophage dif

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