@article{oai:toyama.repo.nii.ac.jp:00005248, author = {Yokozawa, Takako and RHYU, DongYoung and CHO, EunJu and Satoh, Akiko and Hattori, Masao}, issue = {6}, journal = {和漢医薬学雑誌 = Journal of traditional medicines}, month = {Dec}, note = {application/pdf, This study was focused on the protective role of Rhei Rhizoma extract from peroxynitrite (ONOO^-)-induced renal damages. The employed in vivo ONOO^--generation model of lipopolysaccharide plus ischemia-reperfusion resulted in the elevations of plasma 3-nitrotyrosine level and renal myeloperoxidase (MPO) activity as the indicators of in vivo ONOO^- generation. However, the administration of Rhei Rhizoma extract at doses of 30 and 60 mg/kg body weight/day for 30 days significantly decreased the concentrations of 3-nitrotyrosine and MPO activity. In addition, the rats given Rhei Rhizoma extract inhibited xanthine oxidase (XOD) activity but not inducible nitric oxide synthase activity. It suggests that Rhei Rhizoma extract might play the role as a superoxide anion scavenger through the inhibition of XOD activity as well as direct ONOO^- scavenger. The protective role of Rhei Rhizoma extract was also shown in the increase of antioxidant, glutathione, and the reduction in the lipid peroxidation in renal mitochondria. Moreover, the in vivo ONOO^- generation system resulted in the renal functional impairment assessed by the increase in plasma levels of urea nitrogen and creatinine, whereas the rats administered Rhei Rhizoma extract decreased the levels significantly, implying the alleviation of renal dysfunction induced by ONOO^-. This study suggests that Rhei Rhizoma would play the role as an effective therapeutic potential for the oxidative stress-induced renal failure. 本研究は,パーオキシナイトライト(ONOO^-)による腎障害に対する大黄エキスの保護効果について調べた。本実験で用いたin vivo ONOO^-生成のリポポリサッカライド+虚血-再灌流モデルでは,血漿中の3-ニトロテロシンレベルと腎組織中のミエロペルオキシダーゼ(MPO)活性が上昇した。しかし,大黄エキスを30あるいは60mg/kg体重/日を30日間経口投与した群では,3-ニトロチロンンレベルとMPO活性が有意に低下し,キサンテンオキシダーゼ(XOD)活性も低下したが,誘導型-酸化窒素合成酵素活性は変化しなかった。これらの結果から,大黄エキスは直接的なONOO^-消去作用と,XOD活性の阻害による0^-_2消去作用を有することが示唆された。大黄エキスはまた,腎ミトコンドリアの抗酸化物質のグルタチオンレベルを増加し,脂質過酸化レベルが逆に低下していることを確認した。また出所in vivo ONOO^-生成群では,血漿尿素窒素とクレアチニンレベルが増加し,腎機能が低下していたが,大黄エキス投与群ではこれらはいずれも有意に低下し,腎機能の改善作用がみられた。以上より,大黄エキスは酸化ストレスによる腎障害に対し効果的な治療の可能性が示唆された。, Article}, pages = {235--242}, title = {Novel pharmacological potential of Rhei Rhizoma against peroxynitrite-induced oxidative renal injury}, volume = {20}, year = {2003} }