Astragalus Polysaccharide Protect against Cadmium-Induced Cytotoxicity through the MDA5/NF-κB Pathway in Chicken Peripheral Blood Lymphocytes.

Wanqiu Xie,Zequn Tang,Ming Ge,Guangxing Li,Ruyue Li,Linan Zhang,Ruili Zhang

doi:10.3390/molecules22101610

Wanqiu Xie, Zequn Tang + Show 5 more

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https://doi.org/10.3390/molecules22101610

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Abstract

Cadmium (Cd) is a known environmental pollutant that is associated with inflammation, oxidative stress, and cell apoptosis. Astragalus polysaccharide (APS) is a major component of Astragalus membranaceus, a vital qi-reinforcing herb medicine with favorable immuneregulation properties. To study the effect of APS on the inhibition of the cadmium-induced injury of peripheral blood lymphocytes (PBLs) in chickens through the MDA5/NF-κB signaling pathway, PLBs acquired from 15-day-old chickens were divided into control group, Cd group, APS + Cd group, anti-MDA5 mAb + Cd group, BAY 11-7082 (a nuclear factor kappa-light chain-enhancer of activated B cells [NF-κB] inhibitor) +Cd group, APS group, anti-MDA5 mAb group, and BAY 11-7082 group. The transcription levels of melanoma differentiation-associated gene 5 (MDA5), interferon promoter-stimulating factor 1 (IPS-1), NF-κB, and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured by quantitative real-time PCR. MDA5 protein expression was measured by western blotting. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured by corresponding antioxidant kit. The morphological change of PBLs was measured by transmission electron microscopy. The results showed that Cd significantly increased the expression of MDA5, IPS-1, NF-κB, and their downstream cytokines, IL-1β and TNF-α, IL-6 in PLBs. In addition, a high level of MDA was observed in the Cd treatment group; the activities of GSH-Px and SOD were significantly lower in the Cd treatment group than those in controls (p < 0.05). Ultrastructural changes of PBLs showed that Cd promoted autophagy, apoptosis, and necrosis in PBLs. However, APS can efficiently improve Cd-induced cell damage by decreasing the activation of the MDA5 signaling pathway. The effect is consistent with that of anti-MDA5 mAb or/and BAY. The results indicated that APS inhibited Cd-induced cytotoxicity through the regulation of MDA5/NF-κB signaling.

Highlights

Cadmium (Cd), a transition metal, is found widely in the environment, having a significant effect because of its toxicity on human and animal health [1]
N. et al showed that Cd exposure reduced the cell viability of lymphocytes in rodents and humans, and induced oxidative stress, apoptosis, and necrosis [8]
Another study suggested that Cd was capable of inducing apoptosis in murine thymocytes, which is accompanied by a loss in cell viability, significant DNA fragmentation, increased reactive oxygen species (ROS), and mitochondrial membrane depolarization [7]

Summary

Introduction

Cadmium (Cd), a transition metal, is found widely in the environment, having a significant effect because of its toxicity on human and animal health [1]. Molecules 2017, 22, 1610 food chains or through acute or chronic occupational and environmental exposures, resulting in the occurrence of many diseases, even cancers [2], which is retained within the body with little excretion, and when there is an accumulation of the metal within the vital organs, it may produce toxic effects in the kidneys, liver, lungs [3], cardiovascular system, immune system [4], and reproductive system [5,6]. Another study suggested that Cd was capable of inducing apoptosis in murine thymocytes, which is accompanied by a loss in cell viability, significant DNA fragmentation, increased reactive oxygen species (ROS), and mitochondrial membrane depolarization [7]. Björn Fagerberg et al imply that Cd is a possible cause for the increased levels of inflammatory markers and future cardiovascular disease [9]

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