Department of Biological Science and Technology, National Pingtung University of Science and Technology, Pingtung, Taiwan.
J Transl Med. 2012 Jul 19;10:147. doi: 10.1186/1479-5876-10-147.
Nonylphenol (NP), an environmental organic compound, has been demonstrated to enhance reactive-oxygen species (ROS) synthesis. Chronic exposure to low-dose adenine (AD) has been reported to induce chronic kidney disease (CKD).
In this study, we tested the hypothesis that chronic exposure to NP will aggravate AD-induced CKD through increasing generations of inflammation, ROS, and apoptosis that could be attenuated by rosuvastatin. Fifty male Wistar rats were equally divided into group 1 (control), group 2 (AD in fodder at a concentration of 0.25%), group 3 (NP: 2 mg/kg/day), group 4 (combined AD & NP), and group 5 (AD-NP + rosuvastatin: 20 mg/kg/day). Treatment was continued for 24 weeks for all animals before being sacrificed.
By the end of 24 weeks, serum blood urea nitrogen (BUN) and creatinine levels were increased in group 4 than in groups 1-3, but significantly reduced in group 5 as compared with group 4 (all p < 0.05). Histopathology scorings of renal-parenchymal and tubular damages were significantly higher in group 4 than in groups 1-3, but remarkably lower in group 5 compared with group 4 (all p < 0.01). Both gene and protein levels of inflammation, oxidative stress, ROS, and cellular apoptosis were remarkably higher in group 4 compared with groups 1-3, but lowered in group 5 than in group 4 (all p < 0.001). Conversely, both gene and protein levels of anti-oxidants, anti-inflammation and anti-apoptosis were markedly increased in group 5 compared with group 4 (all p < 0.001).
NP worsened AD-induced CKD that could be reversed by rosuvastatin therapy.
壬基酚(NP)是一种环境有机化合物,已被证明能增强活性氧(ROS)的合成。有报道称,慢性低剂量腺嘌呤(AD)暴露会导致慢性肾病(CKD)。
在这项研究中,我们测试了一个假设,即慢性 NP 暴露通过增加炎症、ROS 和细胞凋亡的产生,从而加重 AD 诱导的 CKD,而这种作用可以被瑞舒伐他汀所减弱。50 只雄性 Wistar 大鼠等分为 5 组:第 1 组(对照组)、第 2 组(饲料中 AD 浓度为 0.25%)、第 3 组(NP:2 mg/kg/天)、第 4 组(AD+NP)和第 5 组(AD-NP+瑞舒伐他汀:20 mg/kg/天)。所有动物在 24 周后被处死。
在第 24 周结束时,与第 1-3 组相比,第 4 组的血清血尿素氮(BUN)和肌酐水平升高,但与第 4 组相比,第 5 组明显降低(均 p<0.05)。与第 1-3 组相比,第 4 组的肾实质和肾小管损伤的组织病理学评分明显升高,但与第 4 组相比,第 5 组明显降低(均 p<0.01)。与第 1-3 组相比,第 4 组的炎症、氧化应激、ROS 和细胞凋亡的基因和蛋白水平均显著升高,但第 5 组的水平低于第 4 组(均 p<0.001)。相反,与第 4 组相比,第 5 组的抗氧化剂、抗炎和抗凋亡的基因和蛋白水平均明显升高(均 p<0.001)。
NP 加重了 AD 诱导的 CKD,而瑞舒伐他汀治疗可逆转这一作用。