Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas

Quercetin, a flavonoid antioxidant, prevents and protects streptozotocin-induced oxidative stress and β-cell damage in rat pancreas
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DOI:
10.1016/j.phrs.2004.06.002
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发表时间:
2005-02-01
影响因子:
9.3
通讯作者:
Oter, S
Oter, S
中科院分区:
医学1区
文献类型:
--
作者:
Coskun, O;Kanter, M;Oter, S

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本研究的目的是评价槲皮素(QE)对实验性链脲佐菌素(STZ)诱导的糖尿病大鼠β细胞损伤的可能保护作用。腹腔注射STZ 50 mg/kg诱导糖尿病。QE(15 mg kg-1天,腹膜内(i. p.)注射)在STZ施用之前注射3天;这些注射持续至研究结束(持续4周)。氧化应激在糖尿病的发病机制中起重要作用。为探讨胰腺细胞抗氧化防御系统的变化,测定胰腺组织匀浆中谷胱甘肽过氧化物酶(GSHPx)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性。此外,我们还测量了血清一氧化氮(NO)和红细胞和胰腺组织丙二醛(MDA)水平,脂质过氧化反应的标志物,如果有氧化和抗氧化状态之间的不平衡。用免疫组织化学方法检测胰腺P细胞。STZ可引起脂质过氧化反应和血清NO浓度升高,抗氧化酶活性降低。糖尿病组大鼠红细胞MDA、血清NO和胰腺组织MDA水平显著升高(P < 0.05),抗氧化水平显著降低(P < 0.05)。QE处理显著降低MDA和NO的升高(P < 0.05),提高抗氧化酶活性(P < 0.05)。QE处理可能通过降低脂质过氧化反应、减少NO生成、提高抗氧化酶活性而发挥保护作用。糖尿病大鼠胰岛细胞变性,胰岛素免疫组化染色弱。QE治疗的糖尿病大鼠胰岛素染色增加和胰岛细胞的保护是明显的。这些发现表明QE治疗对糖尿病具有保护作用,通过降低氧化应激和保护胰腺β细胞的完整性。(C)2004爱思唯尔有限公司保留所有权利。
dThe aim of the present study was the evaluation of possible protective effects of quercetin (QE) against beta-cell damage in experimental streptozotocin (STZ)-induced diabetes in rats. STZ was injected intraperitoneally at a single dose of 50 mg kg(-1) for diabetes induction. QE (15 mg kg-1 day, intraperitoneal (i.p.) injection) was injected for 3 days prior to STZ administration; these injections were continued to the end of the study (for 4 weeks). It has been believed that oxidative stress plays a role in the pathogenesis of diabetes mellitus (DM). In order to determine the changes of cellular antioxidant defense system, antioxidant enzymes such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in pancreatic homogenates. Moreover we also measured serum nitric oxide (NO) and erythrocyte and pancreatic tissue malondialdehyde (MDA) levels, a marker of lipid peroxidation, if there is an imbalance between oxidant and antioxidant status. Pancreatic p-cells were examined by inummohistochemical methods. STZ induced a significant increase lipid peroxidation, serum NO concentrations and decreased the antioxidant enzyme activity. Erythrocyte MDA, serum NO and pancreatic tissue MDA significantly increased (P < 0.05) and also the antioxidant levels significantly decreased (P < 0.05) in diabetic group. QE treatment significantly decreased the elevated MDA and NO (P < 0.05), and also increased the antioxidant enzyme activities (P < 0.05). QE treatment has shown protective effect possibly through decreasing lipid peroxidation, NO production and increasing antioxidant enzyme activity. Islet cells degeneration and weak insulin immurrohistochemical staining was observed in STZ induced diabetic rats. Increased staining of insulin and preservation of islet cells were apparent in the QE-treated diabetic rats.These findings suggest that QE treatment has protective effect in diabetes by decreasing oxidative stress and preservation of pancreatic beta-cell integrity. (C) 2004 Elsevier Ltd. All rights reserved.