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PM 2.5 exposure induces systemic inflammation and oxidative stress in an intracranial atherosclerosis rat model
Author(s) -
Guan Longfei,
Geng Xiaokun,
Stone Christopher,
Cosky Eric E. P.,
Ji Yu,
Du Huishan,
Zhang Kezhong,
Sun Qinghua,
Ding Yuchuan
Publication year - 2019
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22707
Subject(s) - oxidative stress , malondialdehyde , nicotinamide adenine dinucleotide phosphate , endocrinology , medicine , superoxide dismutase , chemistry , inflammation , systemic inflammation , tumor necrosis factor alpha , reactive oxygen species , nadph oxidase , oxidase test , biochemistry , enzyme
Objectives Exposure to airborne particle (PM 2.5 ) is a risk factor for intracranial atherosclerosis (ICA). Because of the established role of systemic inflammation and oxidative stress by PM 2.5 , we determined whether these processes account for PM 2.5 ‐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 PM 2.5 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 PM 2.5 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 PM 2.5 exposure, especially in the HCD group. O3FA attenuated ( P < .05) PM 2.5 ‐induced systemic inflammation, vascular oxidative injury, and ICA. Conclusions PM 2.5 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 PM 2.5 .