Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, UAE,
Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, UAE.
Cell Physiol Biochem. 2021 Jan 15;55(1):1-16. doi: 10.33594/000000323.
BACKGROUND/AIMS: Exposure to particulate air pollution is associated with increased cardiovascular morbidity and mortality. These effects are particularly aggravated in patients with pre-existing kidney diseases. Cerium oxide nanoparticles (CNPs), used as diesel fuel additives, are emitted in vehicle exhaust and affect humans when inhaled. However, thrombotic and cardiac injury resulting from pulmonary exposure to CNPs in experimental acute kidney injury (AKI) is not fully understood. The objective of the present study was to evaluate the thrombotic and cardiac injury effects of CNPs in a rat model of AKI.
AKI was induced in rats by a single intraperitoneal injection of cisplatin (CDDP, 6 mg/kg). Six days after injection, rats were intratracheally (i.t.) instilled with either CNPs (1 mg/kg) or saline (control), and various cardiovascular variables and markers of inflammation, oxidative stress and DNA injury were assessed by enzyme linked immunosorbent assay, colorimetric assay, single-cell gel electrophoresis assay and immunohistochemistry, the following day.
Compared with individual CDDP or CNPs treatments, the combined CDDP + CNPs treatment elevated significantly the coagulation function, relative heart weight, and troponin I, lactate dehydrogenase, interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and total nitric oxide levels in the plasma. In heart homogenates, the combination of CDDP and CNPs induced a significant increase in IL-6, TNFα, catalase, and glutathione. Furthermore, significantly more DNA damage was observed in this group than in the CDDP or CNPs groups. Immunohistochemical analysis of the heart revealed that expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) and glutathione peroxidase by cardiac myocytes and endothelial cells was increased in the CDDP + CNPs group more than in either CDDP or CNPs group.
I.t. administration of CNPs in rats with AKI exacerbated systemic inflammation, oxidative stress, and coagulation events. It also aggravated cardiac inflammation, DNA damage, and Nrf2 expression.
背景/目的：暴露于颗粒物空气污染与心血管发病率和死亡率的增加有关。这些影响在患有预先存在的肾脏疾病的患者中尤为严重。氧化铈纳米颗粒（CNP）用作柴油燃料添加剂，在车辆尾气中排放，并在吸入时对人体造成影响。然而，在实验性急性肾损伤（AKI）中，肺部暴露于 CNP 引起的血栓形成和心脏损伤尚不完全清楚。本研究的目的是评估 CNP 在 AKI 大鼠模型中的血栓形成和心脏损伤作用。
通过单次腹腔注射顺铂（CDDP，6mg/kg）诱导 AKI。注射后 6 天，通过气管内（i.t.）滴注 CNP（1mg/kg）或生理盐水（对照），并通过酶联免疫吸附试验、比色法、单细胞凝胶电泳分析和免疫组织化学评估各种心血管变量和炎症、氧化应激和 DNA 损伤标志物，次日。
与单独的 CDDP 或 CNP 处理相比，联合的 CDDP+CNP 处理显著提高了凝血功能、相对心脏重量和肌钙蛋白 I、乳酸脱氢酶、白细胞介素 6（IL-6）、肿瘤坏死因子 α（TNFα）和总一氧化氮水平在血浆中。在心脏匀浆中，CDDP 和 CNP 的联合作用导致 IL-6、TNFα、过氧化氢酶和谷胱甘肽显著增加。此外，与 CDDP 或 CNP 组相比，该组观察到更多的 DNA 损伤。心脏免疫组织化学分析显示，CDDP+CNP 组心肌细胞和内皮细胞的核因子红细胞衍生 2 样 2（Nrf2）和谷胱甘肽过氧化物酶表达增加，高于 CDDP 或 CNP 组。
在 AKI 大鼠中，经气管内给予 CNP 加重了全身炎症、氧化应激和凝血事件。它还加重了心脏炎症、DNA 损伤和 Nrf2 表达。
