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      Metabolomic analysis reveals biogenic selenium nanoparticles improve the meat quality of thigh muscle in heat-stressed broilers is related to the regulation of ferroptosis pathway

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          Abstract

          Heat stress ( HS) causes oxidative damage and abnormal metabolism of muscle, thus impairing the meat quality in broilers. Selenium is an indispensable element for enhancing antioxidant systems. In our previous study, we synthesized a novel type of biogenic selenium nanoparticles synthesized with alginate oligosaccharides ( SeNPs-AOS), and found that the particle size of Se is 80 nm and the Se content is 8% in the SeNPs-AOS; and dietary 5 mg/kg SeNPs-AOS has been shown to be effective against HS in broilers. However, whether SeNPs-AOS can mitigate HS-induced the impairment of thigh muscle quality in broilers is still unclear. Therefore, the purpose of this study was to investigate the protective effects of dietary SeNPs-AOS on meat quality, antioxidant capacity, and metabolomics of thigh muscle in broilers under HS. A total of 192 twenty-one-day-old Arbor Acres broilers were randomly divided into 4 groups with 6 replicates per group (8 broilers per replicate) according to a 2 × 2 experimental design: thermoneutral group (TN, broilers raised under 23±1.5°C); TN+SeNPs-AOS group (TN group supplemented 5 mg/kg SeNPS-AOS); HS group (broilers raised under 33 ± 2°C for 10 h/d); and HS + SeNPs-AOS group (HS group supplemented 5 mg/kg SeNPS-AOS). The results showed that HS increased the freezing loss, cooking loss, and malondialdehyde ( MDA) content of thigh muscle, whereas decreased the total superoxide dismutase ( T-SOD), glutathione peroxidase ( GSH-Px), and catalase ( CAT) activities, as well as downregulated the mRNA expression of SOD2, CAT, GPX3, nuclear factor erythroid 2-related factor 2 ( Nrf2 ), selenoprotein S ( SELENOS ), solute carrier family 7 member 11 ( SLC7A11 ), GPX4, and ferroportin 1 ( Fpn1 ) of thigh muscle ( P < 0.05). Dietary SeNPS-AOS reduced the b* value, elevated the pH 0min value and the activities of T-SOD, GSH-Px, glutathione S-transferase ( GST) and the mRNA expression levels of GSTT1, GSTA3, GPX1, GPX3, ferritin heavy polypeptide-1 ( FTH1 ), and Fpn1 of thigh muscle in broilers under HS ( P < 0.05). Nontargeted metabolomics analysis identified a total of 79 metabolites with significant differences among the four groups, and the differential metabolites were mainly enriched in 8 metabolic pathways including glutathione metabolism and ferroptosis ( P < 0.05). In summary, dietary 5 mg/kg SeNPs-AOS (Se content of 8%) could alleviate HS-induced impairment of meat quality by improving the oxidative damage, metabolic disorders and ferroptosis of thigh muscle in broilers challenged with HS. Suggesting that the SeNPs-AOS may be used as a novel nano-modifier for meat quality in broilers raised in thermal environment.

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          Ferroptosis: process and function.

          Ferroptosis is a recently recognized form of regulated cell death. It is characterized morphologically by the presence of smaller than normal mitochondria with condensed mitochondrial membrane densities, reduction or vanishing of mitochondria crista, and outer mitochondrial membrane rupture. It can be induced by experimental compounds (e.g., erastin, Ras-selective lethal small molecule 3, and buthionine sulfoximine) or clinical drugs (e.g., sulfasalazine, sorafenib, and artesunate) in cancer cells and certain normal cells (e.g., kidney tubule cells, neurons, fibroblasts, and T cells). Activation of mitochondrial voltage-dependent anion channels and mitogen-activated protein kinases, upregulation of endoplasmic reticulum stress, and inhibition of cystine/glutamate antiporter is involved in the induction of ferroptosis. This process is characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS) derived from iron metabolism and can be pharmacologically inhibited by iron chelators (e.g., deferoxamine and desferrioxamine mesylate) and lipid peroxidation inhibitors (e.g., ferrostatin, liproxstatin, and zileuton). Glutathione peroxidase 4, heat shock protein beta-1, and nuclear factor erythroid 2-related factor 2 function as negative regulators of ferroptosis by limiting ROS production and reducing cellular iron uptake, respectively. In contrast, NADPH oxidase and p53 (especially acetylation-defective mutant p53) act as positive regulators of ferroptosis by promotion of ROS production and inhibition of expression of SLC7A11 (a specific light-chain subunit of the cystine/glutamate antiporter), respectively. Misregulated ferroptosis has been implicated in multiple physiological and pathological processes, including cancer cell death, neurotoxicity, neurodegenerative diseases, acute renal failure, drug-induced hepatotoxicity, hepatic and heart ischemia/reperfusion injury, and T-cell immunity. In this review, we summarize the regulation mechanisms and signaling pathways of ferroptosis and discuss the role of ferroptosis in disease.
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            The Metabolic Underpinnings of Ferroptosis

            Acute or chronic cellular stress resulting from aberrant metabolic and biochemical processes may trigger a pervasive non-apoptotic form of cell death, generally known as ferroptosis. Ferroptosis is unique among the different cell death modalities, as it has been mostly linked to pathophysiological conditions and because several metabolic pathways, such as (seleno)thiol metabolism, fatty acid metabolism, iron handling, mevalonate pathway, and mitochondrial respiration, directly impinge on the cells' sensitivity toward lipid peroxidation and ferroptosis. Additionally, key cellular redox systems, such as selenium-dependent glutathione peroxidase 4 and the NAD(P)H/ferroptosis suppressor protein-1/ubiquinone axis, are at play that constantly surveil and neutralize oxidative damage to cellular membranes. Since this form of cell death emerges to be the root cause of a number of diseases and since it offers various pharmacologically tractable nodes for therapeutic intervention, there has been overwhelming interest in the last few years aiming for a better molecular understanding of the ferroptotic death process.
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              Ferroptosis

              Iron is an essential micronutrient for microorganisms, plants, animals, and humans. However, iron overload can damage the organism through a variety of mechanisms, including the induction of cell death. Ferroptosis is defined as an iron-dependent form of regulated cell death caused by unrestricted lipid peroxidation and subsequent membrane damage. Ferroptosis can be triggered through either the extrinsic or the intrinsic pathway. The extrinsic pathway is initiated through the regulation of transporters (e.g., inhibition of the amino acid antiporter system xc- or activation of the iron transporters transferrin and lactotransferrin), whereas the intrinsic pathway is mainly induced by blocking the expression or activity of intracellular antioxidant enzymes, such as glutathione peroxidase 4 (GPX4). In addition to small-molecule compounds and drugs, certain stresses (e.g., high temperature, low temperature, hypoxia, and radiation) induce ferroptotic cell death. The abnormal regulation of this process, which is connected to protein degradation pathways, such as autophagy and the ubiquitin-proteasome system, is associated with various pathological conditions, including acute tissue damage, infection, cancer, and neurodegeneration. Here, we discuss the core process and regulation of ferroptosis in mammalian cells, as well as its therapeutic implications in disease.
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                Author and article information

                Contributors
                Journal
                Poult Sci
                Poult Sci
                Poultry Science
                Elsevier
                0032-5791
                1525-3171
                15 February 2024
                April 2024
                15 February 2024
                : 103
                : 4
                : 103554
                Affiliations
                [* ]Department of Animal Science, College of Coastal Agricultural Science, Guangdong Ocean University, Zhanjiang 524088, China
                []Yangjiang Campus of Guangdong Ocean University, Yangjiang, 529500, China
                Author notes
                [1 ]Corresponding author: liuwc@ 123456gdou.edu.cn
                Article
                S0032-5791(24)00133-0 103554
                10.1016/j.psj.2024.103554
                10906527
                38401225
                5140cb87-2385-43bc-bda2-9565754be1dd
                © 2024 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 13 November 2023
                : 9 February 2024
                Categories
                METABOLISM AND NUTRITION

                ferroptosis,heat stress,metabolomics,meat quality,nano-selenium

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