title: Intraperitoneal exposure of whitefish to microcystin-LR induces rapid liver injury followed by regeneration and resilience to subsequent exposures.
abstract: To date, there has been no systematic approach comprehensively describing the sequence of pathological changes in fish during prolonged exposure to microcystin-LR (MC-LR). Towards this aim, juvenile whitefish individuals received an intraperitoneal injection with pure MC-LR, and the injection was repeated every week to maintain continuous exposure for 28days. During the exposure period, growth and condition of the fish were assessed based on biometric measurements. Additionally, selected biochemical markers were analysed in the fishes' blood, and their livers were carefully examined for morphological, ultrastructural, and molecular changes. The higher dose of MC-LR (100μg·kg-1) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10μg·kg-1) caused less, probably reversible injury, and its effects began to be observed later in the exposure period. These marked changes were accompanied by substantial MC-LR uptake by the liver. However, starting on the 7th day of exposure, cell debris began to be removed by phagocytes, then by 14th day, proliferation of liver cells had markedly increased, which led to reconstruction of the liver parenchyma at the end of the treatment. Surprisingly, despite weekly-repeated intraperitoneal injections, MC-LR did not accumulate over time of exposure which suggests its limited uptake in the later phase of exposure. In support, mRNA expression of the membrane transport protein oatp1d was decreased at the same time as the regenerative processes were observed. Our study shows that closing of active membrane transport may serve as one defence mechanism against further MC-LR intoxication.
authors.affiliation: Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland. Electronic address: maciej.wozny@uwm.edu.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Woźny
authors.affiliation: Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Lewczuk
authors.affiliation: Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Ziółkowska
authors.affiliation: Department of Ichthyology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 5, 10-719 Olsztyn, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gomułka
authors.affiliation: Department of the Salmonid Research in Rutki, Inland Fisheries Institute in Olsztyn, Rutki, 83-330 Żukowo, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dobosz
authors.affiliation: Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Łakomiak
authors.affiliation: Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Florczyk
authors.affiliation: Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Brzuzan
mesh_terms: D000818:Animals; D002843:Chromatin / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008115:Liver Regeneration / Q000187:drug effects*; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D012487:Salmonidae
chemical_list: D002843:Chromatin; D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR
keywords: Apoptosis; Cyanobacteria; Fishes; Histopathology; Regeneration; Tissue distribution