Potential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo.
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(-).
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan. yokozawa@ms.toyama-mpu.ac.jp
Takako
T
Yokozawa
Cui Ping
CP
Chen
Dong Young
DY
Rhyu
Takashi
T
Tanaka
Jong Cheol
JC
Park
Kenichi
K
Kitani
D000818:Animals; D001806:Blood Urea Nitrogen; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects*; D004195:Disease Models, Animal; D047348:Hydrolyzable Tannins; D007511:Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D030421:Peroxynitrous Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D031993:Sanguisorba; D013634:Tannins / Q000737:chemistry / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
D047348:Hydrolyzable Tannins; D008070:Lipopolysaccharides; D013634:Tannins; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; C081844:sanguiin H 6; D003404:Creatinine; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases