Hadzi-Petrushev Nikola, Mitrov Dine, Kostovski Vladimir, Mladenov Mitko
.
J Basic Clin Physiol Pharmacol. 2017 Sep 26;28(5):473-481. doi: 10.1515/jbcpp-2016-0150.
Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.
Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.
The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B2.
Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B2 excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.
氧化应激和炎症参与对乙酰氨基酚诱导的肾损伤发病机制。本研究探讨8-异前列腺素F2α（8-iso-PGF2α）与血小板活化之间的关系，以及促炎标志物白细胞介素（IL）-1β和肿瘤坏死因子-α（TNF-α）在增强8-iso-PGF2α生物合成中的相对作用，这是慢性对乙酰氨基酚治疗诱导的镇痛性肾病中的一个补充发病过程。还研究了维生素C对上述情况的保护作用。
在Wistar大鼠中诱导镇痛性肾病。用分光光度法测定肾功能标志物和抗氧化酶活性。采用免疫测定法测量促炎标志物、脂质过氧化标志物和血小板活化标志物。
对乙酰氨基酚的慢性治疗导致肾功能障碍，表现为血浆尿素和肌酐升高以及酶促抗氧化状态下降，但未导致TNF-α和IL-1β显著增加。对乙酰氨基酚诱导的脂质过氧化和8-iso-PGF2α产生增加不足以引起以11-脱氢血栓素B2水平表示的血小板活化变化。
我们的结果表明，在镇痛性肾病期间，氧化应激无法绕过循环细胞因子刺激的需求来诱导炎症反应和血小板活化变化。维生素C被证明有助于将肾功能标志物恢复正常，增加肾脏酶促抗氧化潜力，抑制脂质过氧化，并降低细胞因子产生和11-脱氢血栓素B2排泄。观察到的维生素C的作用支持其在慢性对乙酰氨基酚过量病例中作为保护性治疗的潜在用途。
