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Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury

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Abstract

Kidney ischemia and reperfusion injury (IRI) is associated with a high mortality rate, which is attributed to tubular oxidative stress and necrosis; however, an effective approach to limit IRI remains elusive. Spermidine, a naturally occurring polyamine, protects yeast cells against aging through the inhibition of oxidative stress and necrosis. In the present study, spermidine supplementation markedly attenuated increases in plasma creatinine concentration and tubular injury score after IRI. In addition, exogenous spermidine potently inhibited oxidative stress, especially lipid peroxidation after IRI in kidneys and exposure to hydrogen peroxide in kidney proximal tubular cells, suppressing plasma membrane disruption and necrosis. Consistent with spermidine supplementation, upregulation of ornithine decarboxylase (ODC) in human kidney proximal tubular cells significantly diminished lipid peroxidation and necrosis induced by hydrogen peroxide-induced injury. Conversely, ODC deficiency significantly enhanced lipid peroxidation and necrosis after exposure to hydrogen peroxide. Finally, small interfering RNA-mediated ODC inhibition induced functional and histological damage in kidneys as well as it increased lipid hydroperoxide levels after IRI. In conclusion, these data suggest that spermidine level determines kidney proximal tubular damage through oxidative stress and necrosis induced by IRI, and this finding provides a novel target for prevention of tubular damage induced by IRI.

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Acknowledgements

The author thanks Youngsu Cho (JNU) for technical assistance with western blot and cell culture. This work was supported by a research grant from the Jeju National University Hospital Research Fund of Jeju National University in 2015.

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  1. Department of Anatomy, Jeju National University School of Medicine, 102 Jejudaehak-ro, Jeju, 63243, Republic of Korea

    Jinu Kim

  2. Department of Biomedicine and Drug Development, Jeju National University, Jeju, 63243, Republic of Korea

    Jinu Kim

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Kim, J. Spermidine rescues proximal tubular cells from oxidative stress and necrosis after ischemic acute kidney injury. Arch. Pharm. Res. 40, 1197–1208 (2017). https://doi.org/10.1007/s12272-017-0957-3

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