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PM2.5 exposure induces systemic inflammation and oxidative stress in an intracranial atherosclerosis rat model

Author:
Guan, Longfei, Geng, Xiaokun, Stone, Christopher, Cosky, Eric E. P., Ji, Yu, Du, Huishan, Zhang, Kezhong, Sun, Qinghua, Ding, Yuchuan
Source:
Environmental toxicology 2019 v.34 no.4 pp. 530-538
ISSN:
1520-4081
Subject:
adults, air, animal models, atherosclerosis, blood serum, brain, dietary supplements, enzyme-linked immunosorbent assay, gene expression regulation, high fat diet, inflammation, interferon-gamma, interleukin-1beta, interleukin-6, laboratory animals, malondialdehyde, messenger RNA, omega-3 fatty acids, oxidative stress, particulates, protective effect, protein content, rats, reactive oxygen species, risk factors, superoxide dismutase, tumor necrosis factor-alpha
Abstract:
OBJECTIVES: Exposure to airborne particle (PM₂.₅) is a risk factor for intracranial atherosclerosis (ICA). Because of the established role of systemic inflammation and oxidative stress by PM₂.₅, we determined whether these processes account for PM₂.₅‐mediated ICA, and also whether omega‐3 fatty acid (O3FA) dietary supplementation could attenuate them. METHODS: Adult Sprague‐Dawley rats were exposed to filtered air (FA) or PM₂.₅ and fed either a normal chow diet (NCD) or a high‐cholesterol diet (HCD), administered with or without O3FA (5 mg/kg/day by gavage) for 12 weeks. The lumen and thickness of the middle cerebral artery (MCA) were assessed. Serum tumor necrosis factor alpha (TNF‐α), interleukin 6 (IL‐6), interleukin‐1β (IL‐1β), and interferon gamma (IFN‐γ) were detected by ELISA. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) activity, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activity, mRNA levels of Nrf2, HO‐1, NQO‐1, and protein level of NOX subunit gp91 were quantified to determine the oxidative profile of brain vessels. RESULTS: PM₂.₅ increased (P < .05) ICA, especially in the HCD group; elevated serum TNF‐α, IL‐6, IL‐1β, and IFN‐γ; increased cerebrovascular ROS, MDA, NOX activity, and gp91 protein levels; and decreased cerebrovascular SOD activity. Nrf2, HO‐1, and NQO‐1 mRNA levels were upregulated (P < .05) by PM₂.₅ exposure, especially in the HCD group. O3FA attenuated (P < .05) PM₂.₅‐induced systemic inflammation, vascular oxidative injury, and ICA. CONCLUSIONS: PM₂.₅ exposure induced systemic inflammation, cerebrovascular oxidative injury, and ICA in rats with HCD. O3FA prevented ICA development, and may therefore exert a protective effect against the atherogenic potential of PM₂.₅.
Agid:
6324437