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Open AccessArticle

Aortic Oxidative Stress, Inflammation and DNA Damage Following Pulmonary Exposure to Cerium Oxide Nanoparticles in a Rat Model of Vascular Injury

1
Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, Abu Dhabi, UAE
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Department of Pharmacology, College of Medicine & Health Sciences, Sultan Qaboos University, P.O. Box 35, Muscat 123, Al-Khoud, Oman
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(8), 376; https://doi.org/10.3390/biom9080376
Received: 17 June 2019 / Revised: 28 July 2019 / Accepted: 29 July 2019 / Published: 17 August 2019
Pulmonary exposure to cerium oxide nanoparticles (CeO2 NPs) can occur either at the workplace, or due to their release in the environment. Inhaled CeO2 NPs are known to cross the alveolar–capillary barrier and reach various parts of the body, including the vasculature. The anticancer drug cisplatin (CP) causes vascular damage. However, the effects CeO2 NPs on vascular homeostasis in a rat model of CP-induced vascular injury remain unclear. Here, we assessed the impact and underlying mechanism of pulmonary exposure to CeO2 NPs on aorta in rats given a single intraperitoneal injection of cisplatin (CP, 6 mg/kg) to induce vascular damage. Six days later, the rats were intratracheally instilled with either CeO2 NPs (1 mg/kg) or saline (control), and various variables were studied 24 h thereafter in the aortic tissue. The concentration of reduced glutathione and the activity of catalase were significantly increased in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. The activity of superoxide dismutase was significantly decreased in the CP + CeO2 NPs group compared with both the CP + saline and CeO2 NPs groups. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2) by the nuclei of smooth muscles and endocardial cells assessed by immunohistochemistry was significantly augmented in CeO2 NPs versus saline, in CP + saline versus saline, and in CP + CeO2 NPs versus CeO2 NPs. Moreover, the concentrations of total nitric oxide, lipid peroxidation and 8-hydroxy-2-deoxyguanosine were significantly elevated in the CP + CeO2 NPs group compared with both the CP + saline and the CeO2 NPs groups. Similarly, compared with both the CP + saline and CeO2 NPs groups, the combination of CP and CeO2 NPs significantly elevated the concentrations of interleukin-6 and tumour necrosis factor-α. Additionally, aortic DNA damage assessed by Comet assay was significantly increased in CeO2 NPs compared with saline, and in CP + saline versus saline, and all these effects were significantly aggravated by the combination of CP and CeO2 NPs. We conclude that pulmonary exposure to CeO2 NPs aggravates vascular toxicity in animal model of vascular injury through mechanisms involving oxidative stress, Nrf2 expression, inflammation and DNA damage. View Full-Text
Keywords: Cerium oxide nanoparticles; aorta; inflammation; oxidative stress; Nrf2; DNA damage Cerium oxide nanoparticles; aorta; inflammation; oxidative stress; Nrf2; DNA damage
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Nemmar, A.; Al-Salam, S.; Beegam, S.; Yuvaraju, P.; Ali, B.H. Aortic Oxidative Stress, Inflammation and DNA Damage Following Pulmonary Exposure to Cerium Oxide Nanoparticles in a Rat Model of Vascular Injury. Biomolecules 2019, 9, 376.

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