Anat Cell Biol.  2018 Sep;51(3):189-199. 10.5115/acb.2018.51.3.189.

Exogenous spermidine ameliorates tubular necrosis during cisplatin nephrotoxicity

Affiliations
  • 1Department of Anatomy, Jeju National University School of Medicine, Jeju, Korea. jinu.kim@jejunu.ac.kr

Abstract

The hallmark of cisplatin-induced acute kidney injury is the necrotic cell death in the kidney proximal tubules. However, an effective approach to limit cisplatin nephrotoxicity remains unknown. Spermidine is a polyamine that protects against oxidative stress and necrosis in aged yeasts, and the present study found that exogenous spermidine markedly attenuated tubular necrosis and kidney dysfunction, but not apoptosis, during cisplatin nephrotoxicity. In addition, exogenous spermidine potently inhibited oxidative/nitrative DNA damage, poly(ADP-ribose) polymerase 1 (PARP1) activation and ATP depletion after cisplatin injection. Conversely, inhibition of ornithine decarboxylase (ODC) via siRNA transfection in vivo significantly increased DNA damage, PARP1 activation and ATP depletion, resulting in acceleration of tubular necrosis and kidney dysfunction. Finally, exogenous spermidine removed severe cisplatin injury induced by ODC inhibition. In conclusion, these data suggest that spermidine protects kidneys against cisplatin injury through DNA damage and tubular necrosis, and this finding provides a novel target to prevent acute kidney injury including nephrotoxicity.

Keyword

Cisplatin; Nephrotoxicity; Spermidine; Lipid peroxidation; Necrosis; Ornithine decarboxylase

MeSH Terms

Acceleration
Acute Kidney Injury
Adenosine Triphosphate
Apoptosis
Cell Death
Cisplatin*
DNA Damage
Kidney
Lipid Peroxidation
Necrosis*
Ornithine Decarboxylase
Oxidative Stress
Poly(ADP-ribose) Polymerases
RNA, Small Interfering
Spermidine*
Transfection
Yeasts
Adenosine Triphosphate
Cisplatin
Ornithine Decarboxylase
Poly(ADP-ribose) Polymerases
RNA, Small Interfering
Spermidine
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