Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats
Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats
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DOI：
10.1007/s00726-012-1225-y
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发表时间：
2012-10-01
期刊：
影响因子：
3.5
通讯作者：
Sil, Parames C.
中科院分区：
文献类型：
--
作者：
Das, Joydeep;Sil, Parames C.
高血糖引起的氧化应激在糖尿病肾病的进展中起着至关重要的作用。牛磺酸的肾脏保护作用也早有报道。但人们对这种有益作用的机制知之甚少。因此，本研究旨在详细探讨牛磺酸在糖尿病条件下的肾脏保护作用的机制。通过给予四氧嘧啶（单次腹腔注射剂量 120 毫克/千克体重）诱导大鼠患糖尿病。从注射四氧嘧啶之日起或糖尿病发病后，口服牛磺酸 3 周（饮用水中 1% w/v）。四氧嘧啶诱导的糖尿病大鼠血浆葡萄糖显着升高，肾损伤标志物、血浆肌酐、尿素氮和尿白蛋白水平升高。糖尿病肾损伤与肾脏重量与体重之比增加和肾小球肥大相关。此外，它还增加了活性氧的产生，增强了脂质过氧化和蛋白质羰基化，同时降低了肾组织细胞内抗氧化防御能力。此外，高血糖会增强促炎细胞因子（TNF-α、IL-6、IL-1β）和Na+-K+-ATP酶活性的水平，同时降低糖尿病肾中NO含量和eNOS表达。对氧化应激反应信号级联的研究表明，糖尿病动物肾组织中 PKC α、PKC β、PKC ε 和 MAP 激酶上调。然而，牛磺酸给药可降低升高的血糖和促炎细胞因子水平，减少肾脏氧化应激（通过降低黄嘌呤氧化酶活性、AGEs形成和抑制p47phox/CYP2E1途径），改善肾功能，并通过调节Bcl-2家族和caspase-9/3蛋白来保护肾组织免受四氧嘧啶诱导的细胞凋亡。因此，在常规饮食中补充牛磺酸可能有益于调节与糖尿病相关的肾脏并发症。
Hyperglycemia-induced oxidative stress plays a vital role in the progression of diabetic nephropathy. The renoprotective nature of taurine has also been reported earlier; but little is known about the mechanism of this beneficial action. The present study has, therefore, been carried out to explore in detail the mechanism of the renoprotective effect of taurine under diabetic conditions. Diabetes was induced in rats by alloxan (single i.p. dose of 120 mg/kg body weight) administration. Taurine was administered orally for 3 weeks (1% w/v in drinking water) either from the day on which alloxan was injected or after the onset of diabetes. Alloxan-induced diabetic rats showed a significant increase in plasma glucose, enhanced the levels of renal damage markers, plasma creatinine, urea nitrogen and urinary albumin. Diabetic renal injury was associated with increased kidney weight to body weight ratio and glomerular hypertrophy. Moreover, it increased the productions of reactive oxygen species, enhanced lipid peroxidation and protein carbonylation in association with decreased intracellular antioxidant defense in the kidney tissue. In addition, hyperglycemia enhanced the levels of proinflammatory cytokins (TNF-alpha, IL-6, IL-1 beta) and Na+-K+-ATPase activity with a concomitant reduction in NO content and eNOS expression in diabetic kidney. Investigation of the oxidative stress-responsive signaling cascades showed the upregulation of PKC alpha, PKC beta, PKC epsilon and MAPkinases in the renal tissue of the diabetic animals. However, taurine administration decreased the elevated blood glucose and proinflammatory cytokine levels, reduced renal oxidative stress (via decrease in xanthine oxidase activity, AGEs formation and inhibition of p47phox/CYP2E1 pathways), improved renal function and protected renal tissue from alloxan-induced apoptosis via the regulation of Bcl-2 family and caspase-9/3 proteins. Taurine supplementation in regular diet could, therefore, be beneficial to regulate diabetes-associated renal complications.