Woźny Maciej, Lewczuk Bogdan, Ziółkowska Natalia, Gomułka Piotr, Dobosz Stefan, Łakomiak Alicja, Florczyk Maciej, Brzuzan Paweł
Department of Environmental Biotechnology, Faculty of Environmental Sciences, University of Warmia and Mazury in Olsztyn, ul. Słoneczna 45G, 10-709 Olsztyn, Poland.
Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, ul. M. Oczapowskiego 13, 10-713 Olsztyn, Poland.
Toxicol Appl Pharmacol. 2016 Dec 15;313:68-87. doi: 10.1016/j.taap.2016.10.014. Epub 2016 Oct 17.
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) caused severe liver injury at the beginning of the exposure period, whereas the lower dose (10μg·kg) 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.
迄今为止，尚未有系统的方法全面描述鱼类在长期接触微囊藻毒素-LR（MC-LR）过程中的病理变化序列。为实现这一目标，对白鲑幼鱼个体进行腹腔注射纯MC-LR，每周重复注射以维持28天的持续接触。在接触期间，基于生物测量评估鱼的生长和状况。此外，分析鱼血液中的选定生化标志物，并仔细检查其肝脏的形态、超微结构和分子变化。较高剂量的MC-LR（100μg·kg）在接触期开始时导致严重肝损伤，而较低剂量（10μg·kg）造成的损伤较小，可能是可逆的，其影响在接触期后期才开始显现。这些显著变化伴随着肝脏对MC-LR的大量摄取。然而，从接触的第7天开始，细胞碎片开始被吞噬细胞清除，到第14天，肝细胞增殖明显增加，这导致治疗结束时肝实质的重建。令人惊讶的是，尽管每周重复腹腔注射，但MC-LR并未在接触期间随时间积累，这表明其在接触后期的摄取有限。作为支持，在观察到再生过程的同时，膜转运蛋白oatp1d的mRNA表达降低。我们的研究表明，关闭主动膜转运可能是一种抵御进一步MC-LR中毒的防御机制。
