Nemmar Abderrahim, Karaca Turan, Beegam Sumaya, Yuvaraju Priya, Yasin Javed, Hamadi Naserddine Kamel, Ali Badreldin H
Cell Physiol Biochem. 2016;38(5):1703-13. doi: 10.1159/000443109. Epub 2016 May 3.
BACKGROUND/AIMS: Epidemiological evidence indicates that patients with chronic kidney diseases have increased susceptibility to adverse outcomes related to long-term exposure to particulate air pollution. However, mechanisms underlying these effects are not fully understood.
Presently, we assessed the effect of prolonged exposure to diesel exhaust particles (DEP) on chronic renal failure induced by adenine (0.25% w/w in feed for 4 weeks), which is known to involve inflammation and oxidative stress. DEP (0.5m/kg) was intratracheally (i.t.) instilled every 4th day for 4 weeks (7 i.t. instillation). Four days following the last exposure to either DEP or saline (control), various renal endpoints were measured.
While body weight was decreased, kidney weight increased in DEP+adenine versus saline+adenine or DEP. Water intake, urine volume, relative kidney weight were significantly increased in adenine+DEP versus DEP and adenine+saline versus saline. Plasma creatinine and urea increased and creatinine clearance decreased in adenine+DEP versus DEP and adenine+saline versus saline. Tumor necrosis factor α, lipid peroxidation and reactive oxygen species were significantly increased in adenine+DEP compared with either DEP or adenine+saline. The antioxidant calase was significantly decreased in adenine+DEP compared with either adenine+saline or DEP. Notably, renal DNA damage was significantly potentiated in adenine+DEP compared with either adenine+saline or DEP. Similarly, systolic blood pressure was increased in adenine+DEP versus adenine+saline or DEP, and in DEP versus saline. Histological evaluation revealed more collagen deposition, higher number of necrotic cell counts and dilated tubules, cast formation and collapsing glomeruli in adenine+DEP versus adenine+saline or DEP.
Prolonged pulmonary exposure to diesel exhaust particles worsen renal oxidative stress, inflammation and DNA damage in mice with adenine-induced chronic renal failure. Our data provide biological plausibility that air pollution aggravates chronic renal failure.
背景/目的:流行病学证据表明,慢性肾病患者因长期暴露于空气中的颗粒物污染而出现不良后果的易感性增加。然而,这些影响背后的机制尚未完全明确。
目前,我们评估了长期暴露于柴油废气颗粒(DEP)对腺嘌呤诱导的慢性肾衰竭(饲料中含0.25% w/w腺嘌呤,持续4周)的影响,已知该过程涉及炎症和氧化应激。每隔4天经气管内(i.t.)注入DEP(0.5mg/kg),持续4周(共7次注入)。在最后一次暴露于DEP或生理盐水(对照)4天后,测量各种肾脏指标。
与生理盐水+腺嘌呤组或DEP组相比,DEP+腺嘌呤组体重下降,但肾脏重量增加。与DEP组相比,腺嘌呤+DEP组的水摄入量、尿量、相对肾脏重量显著增加;与生理盐水组相比,腺嘌呤+生理盐水组的上述指标也显著增加。与DEP组相比,腺嘌呤+DEP组的血浆肌酐和尿素增加,肌酐清除率降低;与生理盐水组相比,腺嘌呤+生理盐水组也有类似变化。与DEP组或腺嘌呤+生理盐水组相比,腺嘌呤+DEP组的肿瘤坏死因子α、脂质过氧化和活性氧显著增加。与腺嘌呤+生理盐水组或DEP组相比,腺嘌呤+DEP组的抗氧化酶过氧化氢酶显著降低。值得注意的是,与腺嘌呤+生理盐水组或DEP组相比,腺嘌呤+DEP组的肾脏DNA损伤显著增强。同样,与腺嘌呤+生理盐水组或DEP组相比,腺嘌呤+DEP组的收缩压升高;与生理盐水组相比,DEP组的收缩压也升高。组织学评估显示,与腺嘌呤+生理盐水组或DEP组相比,腺嘌呤+DEP组有更多的胶原沉积、更多的坏死细胞计数、肾小管扩张、管型形成和肾小球塌陷。
长期经肺部暴露于柴油废气颗粒会加重腺嘌呤诱导的慢性肾衰竭小鼠的肾脏氧化应激、炎症和DNA损伤。我们的数据为空气污染加重慢性肾衰竭提供了生物学合理性依据。