Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy

Katsuyuki Tanabe, Yoshifuru Tamura, Miguel A. Lanaspa, Makoto Miyazaki, Norihiko Suzuki, Waichi Sato, Yohei Maeshima, George F. Schreiner, Francisco J. Villarreal, Richard J. Johnson, Takahiko Nakagawa

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Abstract

Cisplatin nephropathy can be regarded as a mitochondrial disease. Intervention to halt such deleterious injury is under investigation. Recently, the flavanol (-)-epicatechin emerges as a novel compound to protect the cardiovascular system, owing in part to mitochondrial protection. Here, we have hypothesized that epicatechin prevents the progression of cisplatininduced kidney injury by protecting mitochondria. Epicatechin was administered 8 h after cisplatin injury was induced in the mouse kidney. Cisplatin significantly induced renal dysfunction and tubular injury along with an increase in oxidative stress. Mitochondrial damages were also evident as a decrease in loss of mitochondrial mass with a reduction in the oxidative phosphorylation complexes and low levels of MnSOD. The renal damages and mitochondrial injuries were significantly prevented by epicatechin treatment. Consistent with these observations, an in vitro study using cultured mouse proximal tubular cells demonstrated that cisplatin-induced mitochondrial injury, as revealed by a decrease in mitochondrial succinate dehydrogenase activity, an induction of cytochrome c release, mitochondrial fragmentation, and a reduction in complex IV protein, was prevented by epicatechin. Such a protective effect of epicatechin might be attributed to decreased oxidative stress and reduced ERK activity. Finally, we confirmed that epicatechin did not perturb the anticancer effect of cisplatin in HeLa cells. In conclusion, epicatechin exhibits protective effects due in part to its ability to prevent the progression of mitochondrial injury in mouse cisplatin nephropathy. Epicatechin may be a novel option to treat renal disorders associated with mitochondrial dysfunction.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number9
DOIs
Publication statusPublished - Nov 1 2012
Externally publishedYes

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Keywords

  • AKI
  • Cocoa
  • Complex IV
  • Dark chocolate
  • MnSOD

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Tanabe, K., Tamura, Y., Lanaspa, M. A., Miyazaki, M., Suzuki, N., Sato, W., Maeshima, Y., Schreiner, G. F., Villarreal, F. J., Johnson, R. J., & Nakagawa, T. (2012). Epicatechin limits renal injury by mitochondrial protection in cisplatin nephropathy. American Journal of Physiology - Renal Physiology, 303(9). https://doi.org/10.1152/ajprenal.00227.2012