Exogenous spermidine ameliorates tubular necrosis during cisplatin nephrotoxicity

Area of Science:

• Nephrology
• Biochemistry
• Molecular Biology

Background:

• Cisplatin chemotherapy can cause acute kidney injury, characterized by proximal tubule necrosis.
• Current strategies to mitigate cisplatin nephrotoxicity are limited.
• Spermidine, a natural polyamine, has shown protective effects against oxidative stress in other contexts.

Purpose of the Study:

• To investigate the protective effects of exogenous spermidine against cisplatin-induced acute kidney injury.
• To elucidate the molecular mechanisms underlying spermidine's protective action.

Main Methods:

• Administered exogenous spermidine to mice undergoing cisplatin treatment.
• Utilized siRNA to inhibit ornithine decarboxylase (ODC) in vivo.
• Assessed kidney function, tubular necrosis, apoptosis, DNA damage, PARP1 activation, and ATP levels.

Main Results:

• Exogenous spermidine significantly attenuated cisplatin-induced tubular necrosis and kidney dysfunction.
• Spermidine inhibited oxidative/nitrative DNA damage, poly(ADP-ribose) polymerase 1 (PARP1) activation, and ATP depletion.
• ODC inhibition exacerbated cisplatin nephrotoxicity, while spermidine reversed these effects.

Conclusions:

• Spermidine protects kidneys against cisplatin injury by mitigating DNA damage and tubular necrosis.
• The findings suggest spermidine as a novel therapeutic target for preventing acute kidney injury and chemotherapy-induced nephrotoxicity.