Longfei Guan1,2, Xiaokun Geng1,2,3, Christopher Stone2, Eric E P Cosky2, Yu Ji4, Huishan Du1,3, Kezhong Zhang5, Qinghua Sun6, Yuchuan Ding2,7. 1. China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, Beijing, China. 2. Department of Neurosurgery, Wayne State University School of Medicine, Detroit, Michigan. 3. Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, China. 4. Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, China. 5. Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan. 6. Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, Ohio. 7. Department of Research & Development Center, John D. Dingell VA Medical Center, Detroit, Michigan.
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 .
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 .
Authors: Jong Min Kim; Jin Yong Kang; Seon Kyeong Park; Jong Hyun Moon; Min Ji Kim; Hyo Lim Lee; Hye Rin Jeong; Jong Cheol Kim; Ho Jin Heo Journal: Antioxidants (Basel) Date: 2021-11-30