Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat
Pancreatic nitric oxide and oxygen free radicals in the early stages of streptozotocin-induced diabetes mellitus in the rat
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DOI：
10.1590/s0100-879x2000001100012
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发表时间：
2000-11-01
影响因子：
2.3
通讯作者：
Gimeno, M
中科院分区：
文献类型：
--
作者：
González, E;Roselló-Catafau, J;Gimeno, M
本研究的目的是探讨链脲佐菌素（STZ）诱导的胰腺损伤过程中自由基的调节机制，这可能涉及一氧化氮（NO）的产生作为细胞氧化应激的调节剂。通过在聚乙二醇结合的超氧化物歧化酶（PEG-SOD）（1 U/ml）的存在下孵育胰腺组织来去除氧，在糖尿病患者中产生了亚硝酸盐水平（42%）和NO合酶（NOS）活性（50%）的降低，但在对照样品中没有。当NO的产生被N-G-单甲基-L-精氨酸（L-NMMA）（600 μ M）阻断时，SOD活性增加（15.21 +/- 1.23 vs 24.40 +/- 2.01 U/mg干重）。当向孵育培养基中加入NO供体精胺壬酸盐（13.2 +/- 1.32）时，这种增加被消除。当加入PEG-SOD（0.40 +/- 0.02对0.20 +/- 0.03 nmol/mg蛋白质）和L-NMMA阻断孵育介质中的NOS活性（0.28 +/- 0.05）时，糖尿病组织中的脂质过氧化作用较低;精胺壬酸盐（100 μ M）消除了脂质过氧化水平的降低（0.70 +/- 0.02）。我们的结论是，清除氧产生的胰腺NO和NOS水平在STZ治疗的大鼠下降。此外，NOS活性的抑制产生的SOD活性的增加和脂质过氧化在糖尿病胰腺组织中的减少。氧化应激和NO通路在急性STZ诱导的糖尿病大鼠胰腺中相互调节。
The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ)-induced pancreatic damage, which may involve nitric oxide (NO) production as a modulator of cellular oxidative stress. Removal of oxygen species by incubating pancreatic tissues in the presence of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) (1 U/ml) produced a decrease in nitrite levels (42%) and NO synthase (NOS) activity (50%) in diabetic but not in control samples. When NO production was blocked by N-G-monomethyl-L-arginine (L-NMMA) (600 muM), SOD activity increased (15.21 +/- 1.23 vs 24.40 +/- 2.01 U/mg dry weight). The increase was abolished when the NO donor, spermine nonoate, was added to the incubating medium (13.2 +/- 1.32). Lipid peroxidation was lower in diabetic tissues when PEG-SOD was added (0.40 +/- 0.02 vs 0.20 +/- 0.03 nmol/mg protein), and when L-NMMA blocked NOS activity in the incubating medium (0.28 +/- 0.05); spermine nonoate (100 muM) abolished the decrease in lipoperoxide level (0.70 +/- 0.02). We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inhibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and NO pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.