PM_2.5 exposure induces systemic inflammation and oxidative stress in an intracranial atherosclerosis rat model

Abstract

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 . K E Y W O R D Shigh-cholesterol diet, intracranial atherosclerosis, omega-3 fatty acid, PM 2.5 , prevention

Real-Ambient Particulate Matter Exposure-Induced Cardiotoxicity in C57/B6 Mice

“…Specifically, negative effects of Nrf2 in cardiovascular diseases were reported (Barajas et al, 2011;Harada et al, 2012). Particulate matter exposure was also associated with elevated expression of Nrf2, which was abolished by protections (Guan et al, 2019), suggesting that Nrf2 indeed plays roles in PMinduced cardiotoxicity, but this role is not necessarily purely beneficial or purely detrimental. In the current study, it has FIGURE 6 | Survival Plot and MDA contents in serum.…”

The Role of Nrf2 in the PM-Induced Vascular Injury Under Real Ambient Particulate Matter Exposure in C57/B6 Mice

“…At present, the widely recognized mechanism of PMinduced injury is oxidative stress. Among the key factors regulating antioxidant activities, nuclear factor E2-related factor 2 (Nrf2) is a major one, which appeared to be involved in oxidative stress as a protective factor (Guan et al, 2019). Specifically, there was research reported that PM2.5 enhanced the generation of basal ROS and the levels of lipid peroxidation in Nrf2-silenced cells, demonstrating the significance of Nrf2 in maintaining redox balance (Pardo et al,FIGURE 4 | Immunohistochemistry Results of AT1R 6-8 weeks C57/B6 mice, with or without Nrf2 knockout were exposed to either filtered air or air containing particulate matter (PM) for six weeks, and then the vascular tissues were collected,embedded in paraffin and subjected to immunohistochemistry for AT1R.…”

“…As a result, the activated Nrf2 regulates the proteins with antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), heme-oxygenase 1 (HO-1), glutathione peroxidase 1 (GPx-1) and NAD(P)H: quinone oxidoreductase 1 (Tebay et al, 2015). Recent evidences suggested that PM 2.5 could exert oxidative injuries on rat aortic endothelial cells, and the expression of Nrf2 protein in vascular endothelial cells of rats was enhanced (Feng et al, 2016;Guan et al, 2019). Nrf2 may be implicated in vascular endothelial injury induced by PM (Xing et al, 2016).…”

Deciphering the Code between Air Pollution and Disease: The Effect of Particulate Matter on Cancer Hallmarks

“…However, PM exposure has an inflammogenic potential that triggers oxidative stress. For instance, PM 2.5 induces the activation of NADPH oxidase in lung epithelial cells [59] and in the middle cerebral artery of rats [60]. This enzyme produces superoxide anion that is a free radical and precursor of hydrogen peroxide, making a clear contribution to ROS production.…”