ETS-GS, a New Antioxidant, Ameliorates Renal Ischemia-Reperfusion Injury in a Rodent Model

Hagiwara, Satoshi; Koga, Hironori; Iwasaka, Hideo; Kudo, Kyosuke; Hasegawa, Akira; Kusaka, Jyunya; Yokoi, Isao; Noguchi, Takayuki

doi:10.1016/j.jss.2010.01.039

« Previous Next »Journal of Surgical Research
Volume 171, Issue 1 , Pages 226-233, November 2011

ETS-GS, a New Antioxidant, Ameliorates Renal Ischemia-Reperfusion Injury in a Rodent Model

Satoshi Hagiwara, M.D., Ph.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
- To whom correspondence and reprint requests should be addressed at Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi-Yufu City-Oita 879-5593, Japan.
Hironori Koga, M.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
Hideo Iwasaka, M.D., Ph.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
Kyosuke Kudo, M.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
Akira Hasegawa
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
Jyunya Kusaka, M.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan
Isao Yokoi, M.D., Ph.D.
- Department of Physiology, Oita University Faculty of Medicine, Oita, Japan
Takayuki Noguchi, M.D., Ph.D.
- Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, Oita, Japan

Received 24 November 2009 published online 24 February 2010.

Background

Ischemia-reperfusion (I/R) contributes to acute kidney injury (AKI). On the other hand, anti-oxidative drugs help to prevent renal injury caused by I/R. The current study examined whether a new antioxidant, ETS-GS, inhibits reactive oxygen species (ROS) generation and thereby prevents renal I/R injury in rodent models.

Methods

Rats with experimentally-induced renal I/R injury were treated concurrently with an intravenous injection of either ETS-GS or saline. Anesthesia was induced with sevoflurane.

Results

Histologic examination revealed marked reduction of interstitial congestion, edema, inflammation, and hemorrhage in kidney tissue harvested 24 h after ETS-GS treatment. Renal I/R-induced secretion of nitric oxide (NO) in serum was inhibited by ETS-GS treatment. Furthermore, malondialdehyde (MDA) levels in the kidney were significantly lower in ETS-GS-treated rats with renal I/R. Moreover, when murine macrophage-like RAW264.7 cells were stimulated with antimycin A in the presence or absence of simultaneous ETS-GS treatment, ETS-GS decreased ROS levels.

Conclusions

Thus, ETS-GS lowered ROS levels in cultured cells, reduced serum NO levels, decreased renal MDA levels, and protected rats against I/R-induced kidney injury. Given these in vitro and in vivo findings, ETS-GS is a strong candidate for future exploration of therapeutic potential in various human I/R diseases.

Key Words: reactive oxygen species, nitric oxide, acute kidney injury