Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo.

Abstract

Potential of sanguiin H-6, a component of Sanguisorbae Radix, to protect against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite (ONOO(-)) was examined using a model in which rats were injected with lipopolysaccharide (LPS) and then subjected to renal ischemia followed reperfusion (LPS plus ischemia-reperfusion). Ischemia-reperfusion was achieved by occluding bilateral renal artery for 60 min and then releasing for 350 min. At 50 min after ischemia started, LPS was injected intravenously. LPS plus ischemia-reperfusion induced a large amount of 3-nitrotyrosine, an oxidative product of protein that is produced via ONOO(-) nitration, which was not detectable in normal group. Oxidative damage of mitochondria was indicated by an accumulated thiobarbituric acid (TBA)-reactive substance, glutathione (GSH) depletion and glutathione peroxidase (GSH-Px) inactivation in the mitochondria. Treatment of rats with sanguiin H-6 (10 mg/kg body weight/day) for 30 days prior to LPS plus ischemia-reperfusion attenuated the oxidative damage in the mitochondria. The amount of TBA-reactive substance was decreased and the GSH levels significantly increased as compared with that in control group. However, its effect on GSH-Px activity was much weaker. Apoptosis induced by LPS plus ischemia-reperfusion was detected by fluorescence staining, TdT-mediated dUTP-biotin nick end labeling and electrophoretic analysis. Sanguiin H-6 appeared to inhibit apoptosis, and this was associated with the suppression of caspase-3 activity. These beneficial effects of sanguiin H-6 against oxidative damage in mitochondria and apoptosis contributed to the improvement in renal function by reversing the elevated levels of blood urea nitrogen and creatinine caused by ONOO(-).

• Authors: Takako Yokozawa, Cui Ping Chen, Dong Young Rhyu, Takashi Tanaka, Jong Cheol Park, Kenichi Kitani
• Journal: Nephron (Nephron) Vol. 92 Issue 1 Pg. 133-41 (Sep 2002) ISSN: 1660-8151 [Print] Switzerland
• PMID: 12187096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 S. Karger AG, Basel

Chemical References

• Hydrolyzable Tannins
• Lipopolysaccharides
• Tannins
• Peroxynitrous Acid
• 3-nitrotyrosine
• Tyrosine
• sanguiin H 6
• Creatinine
• Casp3 protein, rat
• Caspase 3
• Caspases

Topics

• Animals
• Blood Urea Nitrogen
• Caspase 3
• Caspases (metabolism)
• Creatinine (blood)
• DNA Fragmentation (drug effects)
• Disease Models, Animal
• Hydrolyzable Tannins
• Ischemia (drug therapy, metabolism, pathology)
• Kidney (pathology, physiology)
• Kidney Diseases (drug therapy, metabolism, pathology)
• Lipopolysaccharides
• Male
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Peroxynitrous Acid (metabolism)
• Rats
• Rats, Wistar
• Sanguisorba
• Tannins (chemistry, pharmacology)
• Tyrosine (analogs & derivatives, blood)