Department of Urology, New York Medical College, Valhalla, NY, USA.
Urology. 2013 Aug;82(2):489.e1-7. doi: 10.1016/j.urology.2013.03.065. Epub 2013 Jun 21.
To investigate whether calcium oxalate monohydrate (COM), a key element of hyperoxaluria, would induce renal cell injury through oxidative stress and also whether certain antioxidants could prevent chemically induced renal crystal formation in rats.
COM-exerted oxidative stress on the kidney epithelial Madin-Darby canine kidney cells was assessed using the lipid peroxidation assay. Glyoxalase I (Gly-I) activity was also determined. Two antioxidants, vitamin C and N-acetylcysteine (NAC), were then tested to determine whether they could abolish such oxidative stress in Madin-Darby canine kidney cells. Both antioxidants were also tested to determine whether they might prevent or reduce renal crystal formation induced with ethylene glycol (EG) and vitamin D3 (VD3) in Wistar rats.
COM (200 μg/mL) demonstrated ∼1.3-fold greater oxidative stress with a significant reduction in cell viability and Gly-I activity compared with controls. However, such adverse events were almost completely prevented with NAC but not with vitamin C. In the animal study, no renal crystals were seen in the sham group. However, numerous crystals, with reduced Gly-I activity and elevated oxidative stress, were found in the EG-VD3 group. However, markedly (>70%) fewer crystals, with full Gly-I activity and diminished oxidative stress, were detected in the EG-VD3+NAC group.
COM exerted oxidative stress on Madin-Darby canine kidney cells, leading to cell viability reduction and Gly-I inactivation, with NAC fully preventing such adverse consequences. Similarly, numerous crystals with Gly-I inactivation and elevated oxidative stress seen in the rats (EG-VD3) were also significantly prevented with NAC supplement. Thus, NAC might have clinical implications in preventing oxidative renal cell injury and, ultimately, kidney stone formation.
研究草酸钙一水合物（COM）作为高草酸尿症的关键因素，是否会通过氧化应激引起肾细胞损伤，以及某些抗氧化剂是否可以防止大鼠体内化学诱导的肾晶体形成。
采用脂质过氧化测定法评估 COM 对肾上皮 Madin-Darby 犬肾细胞的氧化应激作用。还测定了糖氧还蛋白 I（Gly-I）的活性。然后测试了两种抗氧化剂，维生素 C 和 N-乙酰半胱氨酸（NAC），以确定它们是否可以消除 Madin-Darby 犬肾细胞中的这种氧化应激。还测试了这两种抗氧化剂是否可以防止或减少乙二醇（EG）和维生素 D3（VD3）诱导的 Wistar 大鼠肾晶体形成。
COM（200μg/ml）表现出约 1.3 倍的氧化应激，细胞活力和 Gly-I 活性显著降低，与对照组相比。然而，NAC 几乎完全阻止了这些不良事件，但维生素 C 却没有。在动物研究中，假手术组未发现肾晶体。然而，在 EG-VD3 组中发现了大量晶体，其 Gly-I 活性降低且氧化应激升高。然而，在 EG-VD3+NAC 组中，晶体数量明显减少（>70%），Gly-I 活性完全，氧化应激减轻。
COM 对 Madin-Darby 犬肾细胞产生氧化应激，导致细胞活力降低和 Gly-I 失活，NAC 完全阻止了这种不良后果。同样，在大鼠（EG-VD3）中观察到的 Gly-I 失活和氧化应激升高的大量晶体也被 NAC 补充显著预防。因此，NAC 可能在预防氧化应激性肾细胞损伤和最终肾结石形成方面具有临床意义。
