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      Cumulative impact of anti-sea lice treatment (azamethiphos) on health status of Rainbow trout ( Oncorhynchus mykiss, Walbaum 1792) in aquaculture

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      1 , 2 , 3 , 1 ,
      Scientific Reports
      Nature Publishing Group UK
      Nephrons, Ichthyology

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          Abstract

          Despite its widespread use in aquaculture, the impact of chemical anti-sea lice treatment on salmonids following application in a commercial farm has not been previously reported. This work reports the cumulative effect of three consecutive anti-sea lice treatments using azamethiphos on the health status of aquaculture reared rainbow trout through the investigation of clinical chemistry, histopathology and proteome expression. The serum biomarkers showed decreasing trends in total protein, albumin and potassium concentrations and an average increase of total bilirubin and phosphate concentration towards the end of the treatment period. Principal component analysis clearly distinguished correlated pairs of biomarkers and also demonstrates a shift from acute to chronic effects as treatment progresses. Proteomic analysis confirmed alterations of proteins involved in clot formation, immune reaction and free heme binding. Tissue damage after the series of delousing treatments, exhibited increased deposits of hemosiderin. Results from this study suggest an impact of azamethiphos on trout health through intravascular haemolysis and consequently from pathophysiologic process of haemoglobin metabolism and its products, causing chronic kidney injury from iron deposits. This is the first report to demonstrate in fish the impact of active iron accumulation in different organs from physiological processes that can seriously impair normal function.

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          The global economic cost of sea lice to the salmonid farming industry.

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            The Cost of Lice: Quantifying the Impacts of Parasitic Sea Lice on Farmed Salmon

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              Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response

              Intravascular hemolysis can result in hemoglobinuria with acute kidney injury. In this study we systematically explored two in vivo animal models and a related cell culture system to identify hemoglobinuria-triggered damage pathways. In models of stored blood transfusion and hemoglobin (Hb) exposure in guinea pigs and beagle dogs we found that hemoglobinuria led to intrarenal conversion of ferrous Hb(Fe2+) to ferric Hb(Fe3+), accumulation of free heme and Hb-cross-linking products, enhanced 4-hydroxynonenal reactivity in renal tissue, and acute tubule injury. These changes were associated in guinea pigs with activation of a renal cortex gene expression signature indicative of oxidative stress and activation of the unfolded protein response (UPR). Tubule cells of hemolytic animals demonstrated enhanced protein expression of heme oxygenase and heat shock protein and enhanced expression of acute kidney injury-related neutrophil gelatinase-associated lipocalin. These adverse changes were completely prevented by haptoglobin treatment. The in vivo findings were extrapolated to a MS-based proteome analysis of SILAC-labeled renal epithelial cells that were exposed to free heme within a concentration range estimate of renal tubule heme exposure. These experiments confirmed that free heme is a likely trigger of tubule barrier deregulation and oxidative cell damage and reinforced the hypothesis that uncontrolled free heme could trigger the UPR as an important pathway of renal injury during hemoglobinuria.
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                Author and article information

                Contributors
                brian.quinn@uws.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                7 November 2019
                7 November 2019
                2019
                : 9
                : 16217
                Affiliations
                [1 ]ISNI 000000011091500X, GRID grid.15756.30, Aquaculture Health Laboratory, School of Health and Life Sciences, University of the West of Scotland, ; Paisley, PA1 2BE Scotland, UK
                [2 ]ISNI 0000 0004 0635 7705, GRID grid.4905.8, Ruđer Bošković Institute, Division of Materials Chemistry, Laboratory for biotechnology in aquaculture, ; Zagreb, Croatia
                [3 ]Kames Fish Farming Ltd., Kilmelford, PA34 4XA Scotland, UK
                Author information
                http://orcid.org/0000-0002-4182-1118
                Article
                52636
                10.1038/s41598-019-52636-1
                6838116
                31700034
                0612c301-b598-450b-afbf-5f00cdc05d43
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 February 2019
                : 12 October 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100012095, Scottish Government;
                Funded by: Scottish Aquaculture Innovation Centre Grant reference number: RD_2016_02
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                © The Author(s) 2019

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                nephrons,ichthyology
                Uncategorized
                nephrons, ichthyology

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