Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats
Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats
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DOI：
10.1006/phrs.2000.0705
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发表时间：
2000-10-01
影响因子：
9.3
通讯作者：
Lee, CS
中科院分区：
文献类型：
--
作者：
Jang, YY;Song, JH;Lee, CS
氧化应激增加被认为与糖尿病组织损伤的发生和发展有关。有几种抗氧化剂被描述为对氧化应激相关疾病有益。冰片碱([S]-2，9-二羟基-1，10-二甲氧基阿朴吗啡)是鸡血藤(Peumus Boldus Molina)叶和树皮中的一种主要生物碱，具有抗氧化和抗炎作用。本实验以雄性大鼠为实验对象，随机分为4组：正常对照组、每日饮水100 mg kg(-1)组、糖尿病[单剂量链脲佐菌素(STZ)80 mg kg(-1)]组。糖尿病患者同时给予冰片治疗8周。观察大鼠血糖和体重的变化，定期评估糖尿病状态。观察冰片对链脲佐菌素诱导的糖尿病大鼠胰腺、肾脏和肝脏线粒体丙二醛和羰基生成及内源性抗氧化酶(超氧化物歧化酶和谷胱甘肽过氧化物酶)活性的影响。研究了冰片对氧自由基的清除作用及对线粒体自由基生成的影响。冰片可减轻STZ所致的大鼠高血糖和体重下降。STZ组大鼠肝、肾、胰腺线粒体丙二醛(MDA)和羰基含量显著升高，冰片碱组降低。STZ组大鼠肝、胰腺、肾脏线粒体锰超氧化物歧化酶(MnSOD)活性显著升高。冰片碱可降低链脲佐菌素引起的肾脏和胰腺线粒体中MnSOD活性的升高，但不影响肝脏线粒体中的MnSOD活性。在STZ治疗组，肝脏线粒体谷胱甘肽过氧化物酶活性降低，胰腺和肾脏线粒体谷胱甘肽过氧化物酶活性升高。博尔丁治疗恢复了肝脏和胰腺中改变的酶活性，但不能恢复肾脏。冰片碱可减轻STZ和铁加抗坏血酸诱导的胰腺匀浆中丙二醛和羰基的形成以及硫醇的氧化。博尔丁对超氧阴离子、过氧化氢和羟基自由基的降解呈剂量依赖关系。结果表明，冰片碱可能通过分解活性氧，抑制一氧化氮的产生，减少过氧化产物的生成，从而抑制STZ引起的氧化损伤和抗氧化酶活性的改变。博尔丁可减轻STZ诱导的大鼠糖尿病的发展，并干预糖尿病的发病机制之一--氧化应激的作用。(C)2000年学术出版社。
Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1,10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated.The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1) of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria.The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus. (C) 2000 Academic Press.